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Nanoparticles in wound healing; from hope to promise, from promise to routine
Abstract
Chronic non-healing wounds represent a growing problem due to their high morbidity and cost. Despite recent advances in wound healing, several systemic and local factors can disrupt the weighed physiologic healing process. This paper critically reviews and discusses the role of nanotechnology in promoting the wound healing process. Nanotechnology-based materials have physicochemical, optical and biological properties unique from their bulk equivalent. These nanoparticles can be incorporated into scaffolds to create nanocomposite smart materials, which promote wound healing through their antimicrobial, as well as selective anti- and pro-inflammatory, and pro-angiogenic properties. Owed to their high surface area, nanoparticles have also been used for drug delivery as well as gene delivery vectors. In addition, nanoparticles affect wound healing by influencing collagen deposition and realignment and provide approaches for skin regeneration and wound healing.
... This makes nanomaterials ideally suited for various biomedical applications such as bone tissue regeneration and wound healing. The latter is mainly initiated in presence of bacteria namely Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa microorganisms which induce a complex series of biochemical processes that could ultimately lead to high mortality rates in developing countries with heavy economic burden (Berthet et al. 2017;Naderi et al. 2018;Unnithan et al. 2014). ...
... Those results disclose that the BGNP containing CA mat had superior antimicrobial properties as compared to un-fabricated CA mats with wide range of activity against the gram positive (Bacillus cereus, Bacillus subtilis and Staphylococcus aureus) and the gram negative (Salmonella tyhimurium and Escherichia coli) bacteria. Worth notably, the BGNP containing CA nanofibers were also effective against Staphylococcus aureus and Escherichia coli strains which represent the most isolated strain from burn and wounds (Berthet et al. 2017;Naderi et al. 2018;Scalise et al. 2015;Unnithan et al. 2014;Zahedi et al. 2010). It was reported that BGs have antimicrobial activity in aqueous solutions due to the release of their ionic compounds over time. ...
Bioactive glasses (BGs) have gained great attention owing to their versatile biological properties. Combining BG nanoparticles (BGNPs) with polymeric nanofibers produced nanocomposites of great performance in various biomedical applications especially in regenerative medicine. In this study, a novel nanocomposite nanofibrous system was developed and optimized from cellulose acetate (CA) electrospun nanofibers containing different concentrations of BGNPs. Morphology, IR and elemental analysis of the prepared electrospun nanofibers were determined using SEM, FT-IR and EDX respectively. Electrical conductivity and viscosity were also studied. Antibacterial properties were then investigated using agar well diffusion method. Moreover, biological wound healing capabilities for the prepared nanofiber dressing were assessed using in-vivo diabetic rat model with induced wounds. The fully characterized CA electrospun uniform nanofiber (100–200 nm) with incorporated BGNPs exhibited broad range of antimicrobial activity against gram negative and positive bacteria. The BGNP loaded CA nanofiber accelerated wound closure efficiently by the 10th day. The remaining wound areas for treated rats were 95.7 ± 1.8, 36.4 ± 3.2, 6.3 ± 1.5 and 0.8 ± 0.9 on 1st, 5th, 10th and 15th days respectively. Therefore, the newly prepared BGNP CA nanocomposite nanofiber could be used as a promising antibacterial and wound healing dressing for rapid and efficient recovery.
... Compared to conventional dressings, nanocarrier are superior in terms of its ability to carry, protect and sustain appropriate drug release to the wound surface for prolonged exposure for healing. Nanotechnology allows nano-sized materials such as nanotubes [35], nanopores [36], fullerenes [37], liposomes [38], polymeric nanoparticles (NPs) [39], nanoemulsions [40], quantum dots [41], nanofibers (NFs) [42], dendrimers [43], and gold and AgNPs [44] those are introduced as superior treatment options than the conventional therapies [45,46]. Different nanocarrier-based formulations targeted to diabetic chronic wound healing are demonstrated in Fig. 2. ...
... Additionally, these nanoscale delivery systems in wound healing possess improved administration of poorly water-soluble drugs, protection of the active therapeutic against temperature, light, pH degradation or from enzymes at the site of administration and further stimulate proliferation of fibroblasts, reduce inflammation and reduce cytotoxicity of certain drugs [48]. Therefore, the involvement of nanotechnology through the therapeutically active wound dressing in the delivery of growth factors and pro-angiogenesis compounds together with other therapeutic agents (e.g., antimicrobials) serves as a potential revolution in wound treatment [46]. A brief account of different nanocarrier approached towards the treatment of diabetic wounds has been presented in the subsequent section. ...
Wounds associated with diabetes mellitus are the most severe co-morbidities, which could be progressed to cause cell necrosis leading to amputation. Statistics on the recent status of the diabetic wounds revealed that the disease affects 15% of diabetic patients, where 20% of them undergo amputation of their limb. Conventional therapies are found to be ineffective due to changes in the molecular architecture of the injured area, urging novel deliveries for effective treatment. Therefore, recent researches are on the development of new and effective wound care materials. Literature is evident in providing potential tools in topical drug delivery for wound healing under the umbrella of nanotechnology, where nano-scaffolds and nanofibers have shown promising results. The nano-sized particles are also known to promote healing of wounds by facilitating proper movement through the healing phases. To date, focuses have been made on the efficacy of silver nanoparticles (AgNPs) in treating the diabetic wound, where these nanoparticles are known to exploit potential biological properties in producing anti-inflammatory and antibacterial activities. AgNPs are also known to activate cellular mechanisms towards the healing of chronic wounds; however, associated toxicities of AgNPs are of great concern. This review is an attempt to illustrate the use of AgNPs in wound healing to facilitate this delivery system in bringing into clinical applications for a superior dressing and treatment over wounds and ulcers in diabetes patients.
... Nanomaterials 2020, 10, 557 2 of 64 predictable amount of time occurs due to local (e.g., trauma, infections, radiation) and systemic factors (e.g., genetic disorders, diabetes, old age, smoking habit, vitamin deficiencies). However, in most cases, the presence of bacteria and the development of infections are the main causes [2,[6][7][8][9]. Wounds are often colonized by Staphylococcus aureus (S. aureus), Escherichia coli (E. ...
... Nanotechnology tools, particularly NPs, have been recognized as occupying a fundamental role in promoting wound healing, with reports on their exceptional antimicrobial, angiogenesis, immunomodulation, and cell and drug delivery, leading the way to new strategies for improving the response to antimicrobial and tissue regeneration therapies [8]. ...
Wound healing requires careful, directed, and effective therapies to prevent infections and accelerate tissue regeneration. In light of these demands, active biomolecules with antibacterial properties and/or healing capacities have been functionalized onto nanostructured polymeric dressings and their synergistic effect examined. In this work, various antibiotics, nanoparticles, and natural extract-derived products that were used in association with electrospun nanocomposites containing cellulose, cellulose acetate and different types of nanocellulose (cellulose nanocrystals, cellulose nanofibrils, and bacterial cellulose) have been reviewed. Renewable, natural-origin compounds are gaining more relevance each day as potential alternatives to synthetic materials, since the former undesirable footprints in biomedicine, the environment, and the ecosystems are reaching concerning levels. Therefore, cellulose and its derivatives have been the object of numerous biomedical studies, in which their biocompatibility, biodegradability, and, most importantly, sustainability and abundance, have been determinant. A complete overview of the recently produced cellulose-containing nanofibrous meshes for wound healing applications was provided. Moreover, the current challenges that are faced by cellulose acetate-and nanocellulose-containing wound dressing formulations, processed by electrospinning, were also enumerated.
... In the final remodeling phase, a framework of collagen and elastin fibers with proteoglycans and glycoproteins replaces the granulation tissue and initiates the maintenance of equilibrium between matrix production and degradation [25]. Remodeling can last up to a year [32] and, once completed, should be shut down for avoiding exaggerated and/or delayed response [33]. ...
... Changes in the concentration of these macromolecules can influence the differentiated state of cells, whereas the presence of chemical gradients of morphogenetic factors regulates the structure of the growing tissue [16]. Since in chronic wounds the levels of growth factors are known to decrease, local delivery of anti-inflammatory agents and growth factors could restore the natural processes of cell proliferation and migration, angiogenesis and collagen deposition [32,40]. Nanogels may provide long term protection from enzymatic degradation and controlled release of active substances, as discussed below. ...
Nanogels have been widely explored for drug delivery, but their applications in the tissue engineering field are still quite recent. Regenerative medicine also demands controlled delivery of growth factors and other active substances able to promote cell adhesion and guide cell differentiation and tissue formation. Moreover, nanogels could be added to tissue scaffolds for modifying their inner architecture, texture and mechanical properties, which are critical for regulating cell behavior. This review aims to provide an insight into the different roles that nanogels may play for improving tissue regeneration. Last decade literature has been carefully analyzed with a focus on in vivo outcomes. After an introductory section to nanogels, relevant examples of their performance for skin and bone tissue regeneration applications are discussed. Healing of chronic wounds and critical size bone fractures may significantly improve thanks to the use of nanogels solely or in combination with scaffolds. Nanogel roles in regenerating vessels, cardiac tissue, urothelium and urethral muscle tissue are also presented. Overall, the information gathered in the review clearly highlights the relevance of multidisciplinary approaches to design nanogels that can face up to the needs of the regenerative medicine. Nanogels may help bring together researchers working in active ingredient formulation, controlled release, nanomechanics, tissue engineering and scaffolding with the common purpose of developing clinically relevant tools for the complete regeneration of complex tissues.
... In the past decade, several studies have reported the application of nanoparticles for treatment of SCI [12,[24][25][26][27]. Compared with other nanoparticles, mesoporous silica nanoparticles (MSNs) have shown significant benefits as a drug delivery system over traditional drug nanocarriers due to their tailored mesoporous structure and high surface area [28,29]. ...
... Drug delivery remains the main challenge of SCI drug development due to the fast metabolism and/or rapid blood clearance of most SCI drugs, as well as poor diffusion through the blood-spinal cord barrier (BSCB) [43]. It has been suggested that nanotechnologies may promote spinal cord delivery and efficacy of drugs because of an improved pharmacokinetic profile and better neurovascular unit access [12,[24][25][26][27]. However, many of these nanocarriers require complex functional design to achieve targeted delivery of drugs which may restrain their pharmaceutical development [44]. ...
Abstract Acute inflammation is a central component in the progression of spinal cord injury (SCI). Anti-inflammatory drugs used in the clinic are often administered systemically at high doses, which can paradoxically increase inflammation and result in drug toxicity. A cluster-like mesoporous silica/arctigenin/CAQK composite (MSN-FC@ARC-G) drug delivery system was designed to avoid systemic side effects of high-dose therapy by enabling site-specific drug delivery to the spinal cord. In this nanosystem, mesoporous silica was modified with the FITC fluorescent molecule and CAQK peptides that target brain injury and SCI sites. The size of the nanocarrier was kept at approximately 100 nm to enable penetration of the blood–brain barrier. Arctigenin, a Chinese herbal medicine, was loaded into the nanosystem to reduce inflammation. The in vivo results showed that MSN-FC@ARC-G could attenuate inflammation at the injury site. Behavior and morphology experiments suggested that MSN-FC@ARC-G could diminish local microenvironment damage, especially reducing the expression of interleukin-17 (IL-17) and IL-17-related inflammatory factors, inhibiting the activation of astrocytes, thus protecting neurons and accelerating the recovery of SCI. Our study demonstrated that this novel, silica-based drug delivery system has promising potential for clinical application in SCI therapy.
... In the migration phase, replacement occurs of destroyed and damaged tissues by moving epithelial cells and fibroblasts to the wound region. These cells are growing very quickly upon the injury below the dried scab (clot) lead by epithelial thickening by revitalize ( Figure 3) [5][6][7][8][9][10] . Wound management/wound care From the earlier times it has been believed that the wounds heal when they are kept dry. ...
Burn and burn related wounds and other types of wounds pose a serious health, social and economic problems to our society. According to WHO, fire related burns cause annual deaths of more than 3,00,000 people, 95% of which occur in third world countries including India. Conventional treatments of wound involve use of silver sulphadiazine and other antimicrobial agents as ointment and cream. They are greasy in nature and stick to clothes and lack patient compliance. It is now established that effective wound hea ling requires moist environment.
... It was also obvious that the 5% AgNPs loaded CA nanofiber was highly effective against the most common bacteria that exist in burns and wounds namely Staphylococcus aureus and Escherichia coli. [80][81][82][83] The antimicrobial activity reported for BGNPs loaded CA nanofiber might be attributed to the ionic compound release over time once in touch with aqueous medium resulting in increasing the environmental pH and killing of the microbes. 84 Moreover, silica release from the bioactive glass into the medium has been associated with antimicrobial activity. ...
Diabetic wound healing remains a significant challenge due to impaired and delayed healing processes. Recently, nanoscaffold dressings with their intricate architectures gained remarkable attention in regenerative medicine. Herein, electrospun cellulose acetate (CA) nanofiber dressings incorporated with various concentrations of bioglass nanoparticles (BGNPs) and silver nanoparticles (AgNPs) were prepared as novel nanocomposites for possible healing of diabetic wound healing. The prepared dressings were physico-chemically characterized using scan electron microscopy (SEM), Fourier Transform Infra-Red Spectroscopy (FTIR), Energy-dispersive X-ray spectroscopy (EDX) and Thermogravimetric analysis (TGA). The antimicrobial activities for the prepared dressings were firstly evaluated in-vitro and then in-vivo against streptozotocin-induced diabetic rats. FTIR and EDX elemental analyses confirmed the chemical and the structural composition of the prepared electrospun CA/BGNPs/AgNPs nanofiber dressings. SEM analysis revealed uniform, smooth and continuous nanofiber (40–180 nm diameter) that showed higher thermal stability as indicated by TGA analysis. The 3% BGNPs and 5% AgNPs loaded CA nanofibers showed maximal antimicrobial activity specifically against the gram positive Staphylococcus aureus (42 ± 1.9 mm) and the gram negative Escherichia coli (43 ± 2.2 mm) which are the main two bacteria infecting wounds. In vivo study revealed remarkable acceleration in wound healing process with 3% BGNPs and 5% AgNPs combination with maximal efficient wound closure by Day 6 without induction of skin irritation. Therefore, the newly designed CA/BGNPs/AgNPs nanofiber dressing hold promising potential for the management of diabetic wounds.
... NPs affect the healing process of the wound by realignment, collagen deposition, and in wound healing and skin regeneration (Naderi et al., 2018). The combination of NPs with the drug provides a new aspect in clinics. ...
Nanoparticle technology in the modern era serves as various functions but their role in health conditions and generation and modulation of immunity makes it more important in the medical field. It is previously used as a carrier of drug delivery that not only delivers the drug to the targeted site but also prevents its side effects and reduction in dosage. The same discovery lead to its use as a potent vaccine in which adjuvant when mixed with these particles results in the potent activation of immune cells and also increased antigen exposure leading to almost dual development of memory T cells. In recent advances, nanoparticles are being used in diagnostics, and with their immune modulation effect, it is nowadays widely used in therapeutics. Its vital role in the prevention of cancer is considered remarkable. Along with that it also initiates better and stronger immunity against any infection and research is done to study its role as an antimicrobial. These advances in nanotechnology research lead to exploring vast functions in many industries. Nanoparticles are engineered, processed, and modulated because their physiochemical properties are different in different roles in the human body. These physiochemical properties include size, shape, electric charge, surface area, roughness, and modulation. In every field of medicine NPs serve to enhance immune response in one way or another.
... Sometimes wound delays healing in due course, rather turns into chronic because of accompanying anomalies such as Peripheral Arterial Disease, Diabetes, etc. Delay in healing also occurs due to improper post-operative care and infections. Chronic wounds are reluctant to heal resulting in a growing health and economic burden and are also accompanied by an increase in morbidity that eventually amplifies the cost of animal care and management (Naderi et al. 2018). Due to their peculiar characteristics, NPs can be used as a substitute method of wound treatment. ...
Nanotechnology has revolutionized medicine, with a focus on green nanoparticle production that is
both friendly to the environment and cost effective. Biogenic nanoparticles have demonstrated great
potential in wound healing, especially through nanotechnology drug delivery systems such as
micelles, nanoparticles, nanoemulsions, and liposomes. These systems improve wound healing by
lowering medication cytotoxicity, increasing skin penetration, and providing antimicrobial
protection. Zinc oxide (ZnO) nanoparticles are particularly useful due to their antibacterial and
anticancer characteristics. This study addressed the wound healing effects of ZnO nanoparticles in
18 rabbits separated into three groups: control (normal saline), ZnO nanoparticles, and ZnO
ointments. Wound contraction size, hematological, and histology were evaluated on days 0, 5, 10,
and 15. The results showed that ZnO nanoparticles significantly increased wound contraction and
histological parameters such as angiogenesis and re-epithelization when compared to the control and
ZnO ointment groups. The hematological study revealed no infection or harm. In conclusion, ZnO
nanoparticles have better healing and therapeutic properties than ZnO ointment.
... Among these are Liposomes, dendrimers, quantum dots, fullerenes, carbon nanotubes, graphene, titanium oxide, iron, and gold nanoparticles. To encourage angiogenesis, NP-based delivery of ions like calcium and oxygen has been used [91]. NPs have become a crucial tool in various medical and pharmaceutical research areas. ...
The development of innovative wound dressing materials is crucial for effective wound care. It’s an active area of research driven by a better understanding of chronic wound pathogenesis. Addressing wound care properly is a clinical challenge, but there is a growing demand for advancements in this field. The synergy of medicinal plants and nanotechnology offers a promising approach to expedite the healing process for both acute and chronic wounds by facilitating the appropriate progression through various healing phases. Metal nanoparticles play an increasingly pivotal role in promoting efficient wound healing and preventing secondary bacterial infections. Their small size and high surface area facilitate enhanced biological interaction and penetration at the wound site. Specifically designed for topical drug delivery, these nanoparticles enable the sustained release of therapeutic molecules, such as growth factors and antibiotics. This targeted approach ensures optimal cell-to-cell interactions, proliferation, and vascularization, fostering effective and controlled wound healing. Nanoscale scaffolds have significant attention due to their attractive properties, including delivery capacity, high porosity and high surface area. They mimic the Extracellular matrix (ECM) and hence biocompatible. In response to the alarming rise of antibiotic-resistant, biohybrid nanofibrous wound dressings are gradually replacing conventional antibiotic delivery systems. This emerging class of wound dressings comprises biopolymeric nanofibers with inherent antibacterial properties, nature-derived compounds, and biofunctional agents. Nanotechnology, diminutive nanomaterials, nanoscaffolds, nanofibers, and biomaterials are harnessed for targeted drug delivery aimed at wound healing. This review article discusses the effects of nanofibrous scaffolds loaded with nanoparticles on wound healing, including biological (in vivo and in vitro) and mechanical outcomes.
Graphical Abstract
... Nanoparticles due to desired antibacterial, proangiogenic, and antiinflammatory properties, play a key role in wound healing process 21,22 . Besides, bioactive nanoparticles such as diopside nanoparticles act as an efficient wound healing agent 23 . ...
A hydrogel-based wound dressing with desirable properties is necessary for achieving functional skin integrity post-injury. This study focuses on preparing a hydrogel using Alginate/Carboxymethyl cellulose (Alg/CMC) as a base material. To evaluate its regenerative effects on full-thickness wounds, diopside nanoparticles and Botulinum toxin A (BTX-A) were incorporated into the hydrogel along with chorion membrane. The diopside nanoparticles (DNPs) act as a proangiogenic factor, promoting proliferation and regulating inflammation, while the chorion membrane facilitates these processes. Additionally, BTX-A prevents scar formation and aids in wound closure. The nanoparticles and hydrogel were characterized using various techniques, and their cytocompatibility was assessed. In vivo studies and quantitative polymerase chain reaction analysis showed that wound area reduction was significant after two weeks of treatment with the Alg/CMC/ChNPs/DNPs/BTX-A hydrogel. Overall, this scaffold demonstrated potential for promoting tissue regeneration and new epithelization formation, making it a promising candidate for enhancing skin restoration in wound treatments.
... They can be utilized as gene transport vectors to affect internal gene expression and protein manufacturing during wound healing. They can also affect wound healing by altering collagen accumulation and reconfiguration (Naderi et al. 2018;Raval et al. 2019;. Numerous non-toxic, bio-compatible and naturally and synthetically prepared polymers are used for drug delivery (Madawi et al. 2023). ...
Diabetes mellitus (DM) is a metabolic disease that delays the regular stages of the wound's healing process due to delayed inflammatory stages. Due to foot pressure points, chronic foot wounds are ultimately considered the primary cause of lower leg amputation. Diabetic patients have vascular dysfunction and neuropathy, leading to inadequate oxygen supply to the wound area. Statins have a crucial role in the regulation of angiogenesis that could increase vascular endothelial growth factor (VEGF) synthesis. By offering a localized treatment approach while minimizing systemic side effects associated with oral medication, this study aimed to develop statin-loaded nanofilms to determine their stability and safety among healthy individuals as a potential procedure for diabetic wound healing. Simvastatin (SIM) loaded nanofilms formulations (F1-F10) were prepared using the solvent casting method. The formulation was optimized based on tests such as physical appearance, tensile strength, microscopic photographs, morphology, and drug content uniformity. ICH guidelines were followed to determine various parameters (physical appearances, tensile strength, microscopic photographs, morphology, and drug content uniformity) for six-month stability study at three different storage conditions. Safety analysis of the nanofilms was performed on healthy human skin using the Draize skin irritation test. Results showed F7 formulation was considered an optimized formulation as well as stable through the storage period at 4 ± 2°C, 25 ± 2°C, and 40 ± 2 °C. Furthermore, Primary Irritation Index results (PII was 0 showed no irritation in case and control groups) indicate its safety and biocompatibility to skin. Thus, the optimized statin-loaded nanofilm is stable, safe, and non-toxic, which may be used as a potential diabetic wound healing agent.
... This process is of utmost importance as failure to heal may result in postoperative infections. Patients who face delayed healing are more prone to such conditions and the risk is higher if they are diagnosed with conditions like diabetes or peripheral vascular disease [63]. Modern day surgeons and physicians have started to employ the use of hydrogels and other materials like NPs to enhance the rate of wound healing. ...
Since ages, catalysts have played a pivotal role in accelerating the production and lowering the cost of a plethora of industrially important commodities. The latest in the scenario are nanocatalysts, which offer a wide array of advantages ranging from improved reaction rates to higher rates of recyclability. However, factors such as stability and support systems must be fine-tuned to achieve maximum efficiency. In accordance with the principle of sustainability, green synthesis methods have propelled the development of a range of nanocatalysts that can be applied in various domains, such as the food industry and biofuel production. Simultaneously, heterogeneous catalysis is gaining more attention globally, primarily due to the ease of recoverability of the nanocatalysts and in this context, magnetically retrievable nanocatalysts are indeed a boon for the green synthesis and sustainable production. Nanocomposites combining plasmonic and catalytic components with noble metal nanoparticles (Au and Ag) and doped semiconductor nanostructures have gained interest in recent years owing to their utility in multiple sectors by virtue of their ability to convert sunlight to chemical energy. The current review describes some methods for the synthesis of such nanocatalysts and their applications in diverse domains.
Graphical Abstract
... 17,18 Recent advancements in nanotechnology, such as specic physicochemical properties and small size, allow the intracellular delivery of different drugs and biomolecules, protect them from degradation, increase the penetration ability of drugs into the wound, allow the topical application, and enhance the halflife of this agents. 19,20 It results in a decline in repetitive drug application, thus lowering the cost and making them costeffective. 21,22 The metallic nanoparticles possess a high surfaceto-volume ratio, high stability, biocompatibility, safety, and economical rates. ...
Diabetic wounds represent a major issue in medical care and need advanced therapeutic and tissue imaging systems for better management. The utilization of nano-formulations involving proteins like insulin and metal ions plays significant roles in controlling wound outcomes by decreasing inflammation or reducing microbial load. This work reports the easy one-pot synthesis of extremely stable, biocompatible, and highly fluorescent insulin-cobalt core-shell nanoparticles (ICoNPs) with enhanced quantum yield for their highly specific receptor-targeted bioimaging and normal and diabetic wound healing in vitro (HEKa cell line). The particles were characterized using physicochemical properties, biocompatibility, and wound healing applications. FTIR bands at 670.35 cm-1, 849.79, and 973.73 indicating the Co-O bending, CoO-OH bond, and Co-OH bending, respectively, confirm the protein-metal interactions, which is further supported by the Raman spectra. In silico studies indicate the presence of cobalt binding sites on the insulin chain B at 8 GLY, 9 SER, and 10 HIS positions. The particles exhibit a magnificent loading efficiency of 89.48 ± 0.049% and excellent release properties (86.54 ± 2.15% within 24 h). Further, based on fluorescent properties, the recovery process can be monitored under an appropriate setup, and the binding of ICoNPs to insulin receptors was confirmed by bioimaging. This work helps synthesize effective therapeutics with numerous wound-healing promoting and monitoring applications.
... There are now certain dressings that are offered for commercial purchase that include silver nanoparticles. 223 PLGA is one of the many different types of polymeric materials that have been designed to manufacture polymeric nanostructures. It is one of the synthetic polymeric materials that has been utilized most effectively, and the FDA has given it approval for clinical usage for humans as a drug delivery system. ...
Hyperglycemia, a distinguishing feature of diabetes mellitus that might cause a diabetic foot ulcer (DFU), is an endocrine disorder that affects an extremely high percentage of people. Having a comprehensive understanding of the molecular mechanisms underlying the pathophysiology of diabetic wound healing can help researchers and developers design effective therapeutic strategies to treat the wound healing process in diabetes patients. Using nanoscaffolds and nanotherapeutics with dimensions ranging from 1 to 100 nm represents a state-of-the-art and viable therapeutic strategy for accelerating the wound healing process in diabetic patients, particularly those with DFU. Nanoparticles can interact with biological constituents and infiltrate wound sites owing to their reduced diameter and enhanced surface area. Furthermore, it is noteworthy that they promote the processes of vascularization, cellular proliferation, cell signaling, cell-to-cell interactions, and the formation of biomolecules that are essential for effective wound healing. Nanomaterials possess the ability to effectively transport and deliver various pharmacological agents, such as nucleic acids, growth factors, antioxidants, and antibiotics, to specific tissues, where they can be continuously released and affect the wound healing process in DFU. The present article elucidates the ongoing endeavors in the field of nanoparticle-mediated therapies for the management of DFU.
... Metal NPs, including selenium, silver, platinum, gold, aurum, copper, and palladium NPs, along with their oxide compounds like iron oxide, zinc oxide, titanium dioxide, and tantalum oxide NPs, potentially have some therapeutic effects on accelerating wound healing [118][119][120]. Apart from being ideal candidates for drug and gene delivery (as discussed previously), metal NPs provide outstanding properties for wound healing, such as antibacterial activity and healing stimulation. ...
Rapidly growing interest in using nanoparticles (NPs) for biomedical applications has increased concerns about their safety and toxicity. In comparison with bulk materials, NPs are more chemically active and toxic due to the greater surface area and small size. Understanding the NPs’ mechanism of toxicity, together with the factors influencing their behavior in biological environments, can help researchers to design NPs with reduced side effects and improved performance. After overviewing the classification and properties of NPs, this review article discusses their biomedical applications in molecular imaging and cell therapy, gene transfer, tissue engineering, targeted drug delivery, Anti-SARS-CoV-2 vaccines, cancer treatment, wound healing, and anti-bacterial applications. There are different mechanisms of toxicity of NPs, and their toxicity and behaviors depend on various factors, which are elaborated on in this article. More specifically, the mechanism of toxicity and their interactions with living components are discussed by considering the impact of different physiochemical parameters such as size, shape, structure, agglomeration state, surface charge, wettability, dose, and substance type. The toxicity of polymeric, silica-based, carbon-based, and metallic-based NPs (including plasmonic alloy NPs) have been considered separately.
... Nanoparticle carriers have shown promising results in treating acute and chronic wounds due to their physiochemical, optical, and biological properties. Nanocomposites are smart materials that have been synthesized by incorporating the nanoparticles into scaffolds, and they have accelerated wound-healing activity in addition to their antimicrobial, anti-inflammatory, and angiogenic properties [10][11][12]. ...
Abstract: Background: Nutrients are widely used for treating illnesses in traditional medicine. Ginger
has long been used in folk medicine to treat motion sickness and other minor health disorders.
Chronic non-healing wounds might elicit an inflammation response and cancerous mutation. Few
clinical studies have investigated 6-gingerol’s wound-healing activity due to its poor pharmacokinetic
properties. However, nanotechnology can deliver 6-gingerol while possibly enhancing these
properties. Our study aimed to develop a nanophytosome system loaded with 6-gingerol molecules
to investigate the delivery system’s influence on wound healing and anti-cancer activities. Methods:
We adopted the thin-film hydration method to synthesize nanophytosomes. We used lipids
in a ratio of 70:25:5 for DOPC(dioleoyl-sn-glycero-3-phosphocholine): cholesterol: DSPE/PEG2000,
respectively. We loaded the 6-gingerol molecules in a concentration of 1.67 mg/mL and achieved size
reduction via the extrusion technique. We determined cytotoxicity using lung, breast, and pancreatic
cancer cell lines. We performed gene expression of inflammation markers and cytokines according to
international protocols. Results: The synthesized nanophytosome particle sizes were 150.16 � 1.65,
the total charge was 13.36 � 1.266, and the polydispersity index was 0.060 � 0.050. Transmission
electron microscopy determined the synthesized particles’ spherical shape and uniform size. The
encapsulation efficiency was 34.54% � 0.035. Our biological tests showed that 6-gingerol nanophytosomes
displayed selective antiproliferative activity, considerable downregulation of inflammatory
markers and cytokines, and an enhanced wound-healing process. Conclusions: Our results confirm
the anti-cancer activity of PEGylated nanophytosome 6-gingerol, with superior activity exhibited in
accelerating wound healing.
... On the other hand, all the mentioned SLNs and NLCs properties make them optimal also for cosmetic and pharmaceutics applications [249]. In particular, many studies reported the NLCs' ability to improve wound healing by enhancing drug penetration and maintaining skin hydration and moisture [275,276]. Starting from this, Chato-Astrain et al. combined the NLCs properties to bioartificial human dermis substitute for tissue engineering application [277]. In particular, they functionalized fibrinagarose biomaterials with antimicrobial-loaded NLCs to treat infected wounds, typical of severe burns. ...
Over the last decades, nanotechnology applied in medicine (nanomedicine) has sparked great interest from the scientific community, thanks to the possibility to engineer nanostructured materials, including nanoparticles (NPs), for a specific application. Their small size confers them unique properties because they are subject to physical laws in the middle between classical and quantum physics. This review is proposed to explain better how to design a specific NP and clarify the relationship between the type, size, and shape of NPs and the specific medical applications. NPs are classified into inorganic (metallic NPs, quantum dots, carbon-based nanostructures, mesoporous silica NPs) and organic (liposomes and micelles, dendrimers, and polymer NPs). Here, we report an accurate description of the potential of each NPs type focusing on their multiple areas of application, including theranostics drug delivery, imaging, tissue engineering, antimicrobial techniques, and nanovaccines. All these features make NPs a promise to revolutionize the new era of nanomedicine.
... Nanoparticles based delivery platforms like liposomes, dendrimers, quantum dots, carbon nanotubes, graphene have been utilised for improved drug delivery, especially into target sites with the attributes of reduced toxicity and other patient compliance. Iron and titanium oxide, gold or silver nanoparticles, and others have been explored for wound healing efficacy [42].The nanoparticle-based delivery of calcium and oxygen ions help in facilitating the process of angiogenesis [43]. ...
Background
Burn injury is considered one of the critical injuries of the skin. According to WHO (World Health Organization), approximately 3,00,000 deaths are caused each year mainly due to fire burns, with additional deaths attributed to heat and other causes of burn e.g., electric devices, chemical materials, radioactive rays, etc. More than 95% of burn injuries occur in developing countries.
Introduction
Burn injuries have been a prominent topic of discussion in this present era of advancements. Burns are one of the common and devastating forms of trauma. Burn injuries are involved in causing severe damage to skin tissues and various other body parts triggered particularly by fire,blaze, or exposure to chemicals and heated substances. They leave a long-lasting negative impact on the patients in terms of their physical and mental health.
Method
The various methods and bioactive hydrogels, a viable and widely utilised approach for treating chronic wounds remains a bottleneck. Many traditional approaches such as woven material, conventional antimicrobial agents, hydrogel sheets, creams are utilised in wound healing. Nowadays, lipid-based nanoparticles, nanofibres systems, and foam-based formulations heal the wound.
Result
The prepared formulation shows wound healing activity when tested on rat model. The nanofibres containing SSD help in the burn-wound healing study on Male Sprague Dawley (SD) rats. The healing effect on rats was examined by western blot analysis, digital camera observation, and histological analyses.
Conclusion
Burn is also considered the most grievous form of trauma. Nowadays, several large and foam-based formulations are used in wound healing, which heals the wound better than previously existing formulations and is less prone to secondary infection. Recently, nanofiber delivery has piqued the interest of academics over the years because of its excellent features, which include an extraordinarily high surface to volume ratio, a highly porous structure, and tiny pore size.
... Nanoparticles are 100 nanometers (nm) or smaller, and often have unusual and unique chemical and physical properties independent of their macro forms. In the wound environment, nanoparticles can aid the healing process by improving angiogenesis, decreasing inflammation, conferring antimicrobial effects, regulating gene expression, and altering the ECM [89]. Nanoparticles also enable targeted delivery of therapeutics, metals, exogenous RNA, and other organic and inorganic wound treatments; they are most often used in the form of polymeric nanoparticles, nanotubes, micelles, liposomes, nanometals, drug conjugates, and protein carriers. ...
Impaired wound healing can lead to local hypoxia or tissue necrosis and ultimately result in amputation or even death. Various factors can influence the wound healing environment, including bacterial or fungal infections, different disease states, desiccation, edema, and even systemic viral infections such as COVID-19. Silk fibroin, the fibrous structural-protein component in silk, has emerged as a promising treatment for these impaired processes by promoting functional tissue regeneration. Silk fibroin’s dynamic properties allow for customizable nanoarchitectures, which can be tailored for effectively treating several wound healing impairments. Different forms of silk fibroin include nanoparticles, biosensors, tissue scaffolds, wound dressings, and novel drug-delivery systems. Silk fibroin can be combined with other biomaterials, such as chitosan or microRNA-bound cerium oxide nanoparticles (CNP), to have a synergistic effect on improving impaired wound healing. This review focuses on the different applications of silk-fibroin-based nanotechnology in improving the wound healing process; here we discuss silk fibroin as a tissue scaffold, topical solution, biosensor, and nanoparticle.
... The silver nanoparticles' anti-inflammatory or antiphlogistic activity was also noticed along with the anti-microbial effect. This can aid the rapid healing of knee wounds/injuries by providing an antimicrobial environment (Naderi et al., 2018). Recently, an environmentally safe synthetic method was used to produce Bauhinia acuminate flower extract loaded silver nanoparticles to treat the meniscus injury. ...
The knee joint is one of the largest, most complex, and frequently utilized organs in the body. It is very vulnerable to injuries due to activities, diseases, or accident, which lead to or cause knee joint injuries in people of all ages. There are several types of knee joint injuries such as contusions, sprains, and strains to the ligament, tendon injuries, cartilage injuries, meniscus injuries, and inflammation of synovial membrane. To date, many drug delivery systems, e.g. nanoparticles, dendrimers, liposomes, micelles, and exosomes, have been used for the treatment of knee joint injuries. They aim to alleviate or reverse the symptoms with an improvement of the function of the knee joint by restoring or curing it. The nanosized structures show good biodegradability, biocompatibility, precise site-specific delivery, prolonged drug release, and enhanced efficacy. They regulate cell proliferation and differentiation, ECM synthesis, proinflammatory factor secretion, etc. to promote repair of injuries. The goal of this review is to outline the finding and studies of the novel strategies of nanotechnology-based drug delivery systems and provide future perspectives to combat the challenges of knee joint injuries by using nanotechnology.
... Nanomaterials have been developed and widely used in biomedical applications, such as cancer therapy (7)(8)(9)(10), regenerative medicine (11)(12)(13), vaccine or vaccine adjuvants (14)(15)(16)(17), infections (18)(19)(20), and tissue imaging (21)(22)(23). Nanoparticle-based gene therapies prevented lung tissue remodeling in the elastase-induced mouse model of emphysema (24), improved wound healing and regeneration in patients with diabetes (25), and increased angiogenesis in airway transplants (26). There has been extensive research on the development of nanoparticles composed of polymeric, metallic, and ceramic materials that enable efficient biodistribution (27), cell-specific targeting (28)(29)(30), and internalization (31,32). ...
Respiratory disorders are among the most important medical problems threatening human life. The conventional therapeutics for respiratory disorders are hindered by insufficient drug concentrations at pathological lesions, lack of cell-specific targeting, and various bio-barriers in the conducting airways and alveoli. To address these critical issues, various nanoparticle delivery systems have been developed to serve as carriers of specific drugs, DNA expression vectors and RNAs. The unique properties of nanoparticles, such as controlled size and distribution, surface functional groups, high payload capacity, and drug release triggering capabilities, are tailored to specific requirements in drug/gene delivery to overcome major delivery barriers in pulmonary diseases. To avoid off-target effects and improve therapeutic efficacy, nanoparticles with high cell-targeting specificity are essential for successful nanoparticle therapies. Furthermore, low toxicity and high degradability of the nanoparticles are among the most important requirements in the nanoparticle designs. In this review, we provide the most up-to-date research and clinical outcomes in nanoparticle therapies for pulmonary diseases. We also address the current critical issues in key areas of pulmonary cell targeting, bio-safety and compatibility, and molecular mechanisms for selective cellular uptake.
... Other nanoparticles based on copper, graphene, titanium oxide, fibrin, polycations, and zinc oxide were also incorporated in wound dressings and assessed for their antimicrobial activities in vitro and in vivo [99]. Furthermore, recent studies have focused on the development of rapid wound healing approaches based on gene delivery using nanocarriers or the delivery of wound healing promoting factors such as nitric oxide using nanocarriers and were recently reviewed by Naderi et al. [96]. ...
Novel approaches for the management of postoperative pain and wound healing are needed. Most patients who undergo surgery experience acute postoperative pain, but for approximately 10% of patients, the pain becomes chronic. The increasing reliance on opioids has been associated with the rising epidemic of opioid misuse and abuse. Also, the incidence of postoperative nosocomial infection and the resistance of pathogenic bacteria to antibiotics has become a significant health issue. For a few decades, nanomedicines have demonstrated their potential for the treatment of several pathologies in preclinical studies, but so far only a few have been approved in the clinic for the treatment of pain. More recently, nanomaterials have been developed and optimized for drug delivery through the nonparenteral routes. In this chapter, nonparenteral nanomedicines used for the treatment of postoperative pain are presented, as well as the nanoparticles develop to reduce the risk of infection and promote wound healing.
... AgNPs have been used for numerous clinical trials in the therapy of wounds, especially burns and chronic wounds (diabetic wounds). Currently, there are some commercially available dressings containing AgNPs [160]. Among the different polymers developed to fabricate polymeric nanoparticles, PLGA is one of the most successfully used synthetic polymers, with FDA approval for clinical use in humans as a DDS, due to the following desirable properties: (1) well-described formulations and methods of production adapted to various types of drugs, ranging from small molecules to macromolecules; and (2) ability to protect drugs from degradation and the possibility of sustained release [161]. ...
Diabetes mellitus (DM) is a common endocrine disease characterized by a state of hyperglycemia (higher level of glucose in the blood than usual). DM and its complications can lead to diabetic foot ulcer (DFU). DFU is associated with impaired wound healing, due to inappropriate cellular and cytokines response, infection, poor vascularization, and neuropathy. Effective therapeutic strategies for the management of impaired wound could be attained through a better insight of molecular mechanism and pathophysiology of diabetic wound healing. Nanotherapeutics-based agents engineered within 1–100 nm levels, which include nanoparticles and nanoscaffolds, are recent promising treatment strategies for accelerating diabetic wound healing. Nanoparticles are smaller in size and have high surface area to volume ratio that increases the likelihood of biological interaction and penetration at wound site. They are ideal for topical delivery of drugs in a sustained manner, eliciting cell-to-cell interactions, cell proliferation, vascularization, cell signaling, and elaboration of biomolecules necessary for effective wound healing. Furthermore, nanoparticles have the ability to deliver one or more therapeutic drug molecules, such as growth factors, nucleic acids, antibiotics, and antioxidants, which can be released in a sustained manner within the target tissue. This review focuses on recent approaches in the development of nanoparticle-based therapeutics for enhancing diabetic wound healing.
... Nanoparticle delivery systems have been used clinically and experimentally to treat cancer, inflammatory conditions, and complications of diabetes and have demonstrated potential for use in tissue regeneration. Nanoparticle-based therapies can inhibit growth of non-small cell lung cancer (1), improve alveolar structure in chronic obstructive pulmonary disease (2), stimulate wound healing in patients with diabetes (3), and increase microvascular density when applied topically ex vivo to airway transplants (4). These studies highlight the therapeutic potential of nanoparticle technology, and further advances in this field will improve tissue specificity and efficiency of these applications. ...
Rationale:
Advances in neonatal critical care have greatly improved the survival of preterm infants but the long-term complications of prematurity, including Bronchopulmonary dysplasia (BPD), cause mortality and morbidity later in life. While Vascular Endothelial Growth Factor (VEGF) improves lung structure and function in rodent BPD models, severe side effects of VEGF therapy prevent its use in BPD patients.
Objectives:
To test whether nanoparticle delivery of proangiogenic transcription factors FOXM1 or FOXF1, both downstream targets of VEGF, can improve lung structure and function after neonatal hyperoxic injury.
Methods:
Newborn mice were exposed to 75% O2 for 7 days of life before being returned to room air. On postnatal day 2, polyethylenimine-(5) myristic acid/ poly(ethylene glycol)-oleic acid/ cholesterol (PEI600-MA5/PEG-OA/Cho) nanoparticles containing non-integrating expression plasmids with Foxm1 or Foxf1 cDNAs were injected intravenously. The effects of the nanoparticles on lung structure and function were evaluated using confocal microscopy, flow cytometry and the Flexivent small animal ventilator.
Main results:
The nanoparticles efficiently targeted endothelial cells and myofibroblasts in the alveolar region. Nanoparticle delivery of either FOXM1 or FOXF1 did not protect endothelial cells from apoptosis caused by hyperoxia but increased endothelial proliferation and lung angiogenesis after the injury. FOXM1 and FOXF1 improved elastin fiber organization, decreased alveolar simplification and preserved lung function in mice reaching adulthood.
Conclusions:
Nanoparticle delivery of FOXM1 or FOXF1 stimulates lung angiogenesis and alveolarization during recovery from neonatal hyperoxic injury. Delivery of proangiogenic transcription factors has promise as a therapy for BPD in preterm infants.
... 161 Recently, NPs have been incorporated into biological materials to form nanocomposites that promote chronic wound healing through their antibacterial, anti-inflammatory, and proangiogenic properties. 162 Biocompatible hydrogel is a material with great development prospects in the field of medicine and biology. It is widely used in wound healing, medicine, cell delivery, and tissue regeneration. ...
Damage to skin tissue, which causes the disorder of the patient's body homeostasis, threatens the patient's life and increases the personal and social treatment burden. Angiogenesis, a key step in the wound healing process, provides sufficient oxygen and nutrients to the wound area. However, traditional clinical interventions are not enough to stabilize the formation of the vascular system to support wound healing. Due to the unique properties and multiple functions of nanomaterials, it has made a major breakthrough in the application of medicine. Nanomaterials provide a more effective treatment to hasten the angiogenesis and wound healing, by stimulating fundamental factors in the vascular regeneration phase. In the present review article, the basic stages and molecular mechanisms of angiogenesis were analyzed, the types, applications, and prospects of nanomaterials used in angiogenesis were detailed.
... In recent years, lipid-nanoparticles, i.e. solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), have attracted much attention as effective, biodegradable, biocompatible and non-toxic carriers, exhibiting many adequate features for dermal application of cosmetics and pharmaceutics (1). Consequently, SLN and NLC have been broadly considered as suitable and efficient systems for improving wound healing because of their occlusive properties that increase skin hydration and enhance drug penetration (2,3). Therefore, the use of these lipid nanoparticles is an interesting strategy for chronic wound treatment as they promote an appropriate wound bed that could re-activate the healing process. ...
Re-activation of the healing process is a major challenge in the field of chronic wound treatment. For that purpose, lipid-nanoparticles, especially nanostructured lipid carriers (NLC), possess extremely useful characteristics such as biodegradability, biocompatibility and long-term stability, besides being suitable for drug delivery. Moreover, they maintain wound moisture due to their occlusive properties, which have been associated with increased healing rates. In the light of above, NLC have been extensively used topically for wound healing; but to date, there are no safety-preclinical studies concerning such type of application. Thus, in this work, biodistribution studies were performed in rats with the NLC previously developed by our research group, using technetium-99 m (99mTc-NLC) as radiomarker, topically administered on a wound. 99mTc-NLC remained on the wound for 24 h and systemic absorption was not observed after administration. In addition, toxicological studies were performed to assess NLC safety after topical administration. The results obtained demonstrated that NLC were non-cytotoxic, non-sensitizing and non-irritant/corrosive. Overall, it might be concluded that developed NLC remained at the administration area, potentially exerting a local effect, and were safe after topical administration on wounds.
... In recent years, lipid-nanoparticles, i.e. solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), have attracted much attention as effective, biodegradable, biocompatible and non-toxic carriers, exhibiting many adequate features for dermal application of cosmetics and pharmaceutics (Müller et al., 2002). Consequently, SLN and NLC have been broadly considered as suitable and efficient systems for improving wound healing because of their occlusive properties that increase skin hydration and enhance drug penetration (Naderi et al., 2018;Pardeike et al., 2009). Therefore, the use of these lipid nanoparticles is an interesting strategy for chronic wound treatment as they promote an appropriate wound bed that could re-activate the healing process. ...
... Due to their size (<100 nm), these nanoparticles have unique characteristics in terms of shape, high surface area, load, chemical properties, solubility, and degree of agglomeration. Their multifunctionality has enabled their use in various areas of engineering, cosmetic industry, medicine, and the agricultural sector [3,4]. The use of nanoparticles in the agricultural sector has already been reported as sources of fertilizers that increase crop yields, mitigate environmental pressures, and/or increase the nutraceutical quality of plants and fruits, thus generating functional foods [5][6][7][8]. ...
Moringa oleifera Lam is a plant that has recently gained importance as a food because of its nutritional value and bioactive compound content and because practically all the organs are usable. The use of nanoparticles has appeared as an alternative to increase bioactive compounds in plants. The goal of this work was to determine if the application of copper nanoparticles would increase the content of bioactive compounds and antioxidant capacity in M. oleifera. Copper (Cu) nanoparticles were applied to the leaves at four different times throughout crop growth. The biocompounds were analyzed after the second, third, and fourth applications. The results show that application of Cu nanoparticles has a beneficial effect on the accumulation of bioactive compounds in M. oleifera leaves. In addition, the antioxidant capacity and carotenoid and chlorophyll contents in the leaves of M. oleifera increased after Cu nanoparticles application. The same effect was not observed in the fruit of M. oleifera. Here, the bioactive compound contents diminished. Therefore, the use of Cu nanoparticles can be an important alternative to improve the quality of this plant, particularly that of the leaves.
... The composite also eludes nitric oxide to enhance the wound healing. 521 The materials are fabricated to a 3D scaffold and are currently under investigation for wound healing. ...
Research pertaining to conductive polymers has gained significant traction in recent years, and their applications range from optoelectronics to material science. For all intents and purposes, conductive polymers can be described as Nobel Prize-winning materials, given that their discoverers were awarded the Nobel Prize in Chemistry in 2000. In this review, we seek to describe the chemical forms and functionalities of the main types of conductive polymers, as well as their synthesis methods. We also present an in-depth analysis of composite conductive polymers that contain various nanomaterials such as graphene, fullerene, carbon nanotubes, and paramagnetic metal ions. Natural polymers such as collagen, chitosan, fibroin, and hydrogel that are structurally modified for them to be conductive are also briefly touched upon. Finally, we expound on the plethora of biomedical applications that harbor the potential to be revolutionized by conductive polymers, with a particular focus on tissue engineering, regenerative medicine, and biosensors.
... Recently, a range of inorganic nanomaterials have been utilized for developing bionanocomposites in tissue engineering applications, such as silicate-based materials (e.g. clays, silica nanoparticles, bioactive glass), ceramics (nanohydroxyapatite, calcium triphosphate), carbon-based nanomaterials (graphene, fullerenes, carbon nanotubes, etc.), and metal/metal oxides (gold, silver, platinum, iron oxide, zinc oxide, titanium oxide and so on) [6,17,[36][37][38][39][40][41][42][43][44][45][46]. These inorganic nanofillers can not only reinforce the mechanical strengths of the bulk biomaterials [47,48], but also impart additional functionality to the nanocomposite systems. ...
Regeneration of skin tissues with anatomic and functional integrity after injury remains a great challenge due to the complexity of wound healing. In the past decade, numerous efforts have been made to construct engineered nanocomposites with combination of organic polymeric networks and inorganic bioactive nanoparticles for facilitating the healing process. In this review, we aim to critically summarize the state-of-art progress on the bioactive inorganic/organic nanocomposites for wound healing. Followed by a brief discussion on the design principle of inorganic/organic nanocomposites, we describe two typical preparation methods with comments on their advantages and drawbacks in wound healing applications. The current applications of inorganic/organic nanocomposites with particular emphasis on their bioactive characteristics are also presented. Finally, concluding remarks and personal insights on the challenges and outlooks are addressed.
Chronic and infected wounds, particularly those caused by bacterial infections, present significant challenges in medical treatment. This study aimed to develop a novel nanoparticle formulation to enhance wound healing by combining antimicrobial and photothermal therapy using albumin as a carrier for Tanshinone IIA and the near-infrared photothermal agent IR780. The nanoparticles were synthesized to exploit the antimicrobial effects of Tanshinone IIA and the photothermal properties of IR780 when exposed to near-infrared laser irradiation. Characterization of the nanoparticles was performed using Transmission Electron Microscopy (TEM) and spectroscopic analysis to confirm their successful synthesis. In vitro antibacterial activity was evaluated using cultures of methicillin-resistant Staphylococcus aureus (MRSA), and in vivo efficacy was tested in a mouse model of MRSA-infected wounds. Wound healing progression was assessed over 16 days, with statistical analysis performed using two-way ANOVA followed by Tukey’s post-hoc test. The nanoparticles demonstrated significant photothermal properties, enhancing bacterial eradication and promoting the controlled release of Tanshinone IIA. In vitro studies showed superior antibacterial activity, especially under photothermal activation, leading to a substantial reduction in bacterial viability in MRSA cultures. In vivo, nanoparticle treatment combined with near-infrared laser irradiation significantly improved wound closure rates compared to controls and treatments without photothermal activation. By the 16th day post-treatment, significant improvements in wound healing were observed, highlighting the potential of the combined photothermal and pharmacological approach. These findings suggest that albumin-loaded nanoparticles containing Tanshinone IIA and IR780, activated by near-infrared light, could offer an effective therapeutic strategy for managing chronic and infected wounds, promoting both infection control and tissue repair.
A BSTRACT
Aim
The current work intends to examine the antibacterial activity of silver nanoparticles (AgNPs) mediated by Ocimum gratissimum stem extract against wound infections.
Materials and Methods
To evaluate the membrane damage brought on by AgNPs, analyses of cytoplasmic leakage and protein leakage assays were performed.
Results
The outcomes demonstrated that all of the tested bacterial strains were significantly resistant to the AgNPs’ antibacterial activity. AgNPs damaged membranes and caused cellular contents to leak in the target pathogens, according to an examination of protein and cytoplasmic leakage.
Conclusion
According to the current investigation, AgNPs mediated by Ocimum gratissimum stem extract may be effective antibacterial agents against microorganisms that cause wounds.
The skin represents our first defense against physical, mechanical, or biological damage. However, its regeneration potential depends on the degree of the wound and the systemic state. For large acute or chronic wounds, specialized treatments are required to stimulate regeneration and avoid scarring. The use of nanotechnology represents a promising tool to promote wound healing, not only by developing antibacterial nanomaterials to prevent infection, but also by developing nanomaterials capable of enhancing cell proliferation, extracellular matrix deposition, and angiogenesis, as well as regulating inflammation. Nanotechnology offers a new and wide field of application for materials, due to the unique properties of nanomaterials that normally differ from, or are enhanced compared to, bulk materials. Nanomaterial properties changed mainly due to its larger contact area, which normally results in better optical, catalytic, and biodistribution properties. Due to their physical–chemical characteristics, nanoparticles can be tailored in different ways to be delivered and act at the site of injury, improving wound healing. Nanoparticles can be incorporated into different substrates to generate antibacterial coverages, they can be functionalized and tailored to be used as vectors for delivering signaling molecules (growth factors), or their properties such as size, crystallinity, surface chemistry, and shape can be modified to elicit different biological effects. The present work is aimed at resuming the advances of the last decade in nanoparticles used to improve wound healing based on their antimicrobial activity, cell proliferation enhancement, angiogenesis promotion, regulation of extracellular matrix deposition, and anti-inflammatory modulation.
Graphical abstract
Wound healing is a complex physiological procedure that includes diverse stages, comprising hemo-stasis, inflammation, proliferation, and remodeling to reconstruct the skin and subcutaneous tissue's integrity. As reported, various coexisting diseases (diabetes, vascular diseases, etc.) substantially impact wound healing. Factors like recurring injury, age, or hypertrophic scarring also affect wound healing. The management of wound care depends primarily on the advancement of novel and efficient wound dressing substances, and it persists to be a vivid research area in chronic wound healing. Over the past years, the investigation and advancement of wound dressing biomaterials have registered a new standard level, and superior knowledge based on chronic wound pathogenesis has been achieved. Recently, nanotechnology has presented an excellent method to accelerate acute and chronic wound healing via stimulating appropriate movement through the diverse healing stages. Among various nanomaterials, nanoparticles (NPs) have been spotlighted as an efficient treatment strategy for wound healing due to their ability to act as both a therapeutic and carrier system. Their small size and high surface area to volume ratio enhance the probability of bio-interaction and penetration at the wound area aiding cell ecell interactions, the proliferation of cells, cell signaling, and vascularization. This review endeavored to throw light on different aspects of wounds and the latest advances in nanoparticle-based biomaterials for effective wound healing. Further, challenges and future potentialities have been addressed.
Chronic wounds represent a challenge for the health area, as they directly impact patients’ quality of life and represent a threat to public health and the global economy due to their high cost of treatment. Alternative strategies must be developed for cost-effective and targeted treatment. In this scenario, the emerging field of nanobiotechnology may provide an alternative platform to develop new therapeutic agents for the chronic wound healing process. This manuscript aims to demonstrate that the application of metallic nanoparticles (gold, silver, copper, and zinc oxide) opened a new chapter in the treatment of wounds, as they have different properties such as drug delivery, antimicrobial activity, and healing acceleration. Furthermore, metallic nanoparticles (NPs) produced through green synthesis ensure less toxicity in biological tissues, and greater safety of applicability, other than adding the effects of NPs with those of extracts.
Parrotiopsis jacquemontiana (Decne) Rehder aqueous extract of leaf was used for biosynthesis of AgNPs and characterized through UV–Visible spectroscopy, X‐ray diffraction, Fourier‐transform‐infrared, diffraction light scattering, and scanning electron microscope analysis. Moderate to strong antioxidant activity during in vitro antioxidant assays for scavenging of 2,2‐diphenyl‐1‐picryl hydrazyl (DPPH), hydroxyl (OH), nitric oxide (NO) radicals, iron chelation, and inhibition of β‐carotene bleaching was recorded with minimum IC50 value (27.70 ± 2.67 μg/ml) calculated for OH radicals. The AgNPs were evaluated against six multidrug resistant human bacterial strains and minimum inhibitory concentration (MIC) along with minimum bactericidal concentration (MBC) values was determined and all were found remarkably susceptible. The bacterial strain Staphylococcus aureus was the most susceptible with MIC = 5 μg/ml and MBC = 10 μg/ml. Among six fungal strains, Fumigatus esculentum was the most susceptible with MIC and MBC of 10 μg/ml. 3‐(4,5‐Dimethylthiazol‐2 yl)‐2,5‐diphenyltetrazolium bromide (MTT) screening assay against cancer cell lines (HCCLM3, HEPG2, MDA‐MB 231, and MCF‐7) revealed the least IC50 values against HCCLM3 (74.20 ± 5.04) and MCF‐7 (91.90 ± 1.17). While no cytotoxicity against normal cell lines; LO2 and MCF‐10a was recorded. Parrotiopsis jacquemontiana silver nanoparticles (PJAgNPs) significantly (p > .001) prevented the migration of HCCLM3 cells in a dose‐dependent style, relative to control. The wound healing potential of AgNPs in rat was found higher (p < .05) for wound contraction rates, hydroxyproline content, hemostatic and re‐epithelization and regeneration efficiency in comparison to the reference group. Green synthesized AgNPs from Parrotiopsis jacquemontiana. In vitro antioxidant activities. Wound healing activity.
Objective
To optimize radiolabeling with 99mTc and ⁶⁷Ga of albumin nanoparticles coated with 4 differents synthetic polymers and to evaluate their stability in vivo and in vitro, as well as their biodistribution in vivo after intravenous administration.
Material and methods
The nanoparticles were prepared using albumin and NOTA-modified albumin by the desolvation met-hod and coated with 4 different polymers: HPMC, GMN2, GPM2 and GTM2. They were purified, lyophilized and characterized. Radiolabelling with 99mTc was performed with 74 MBq of 99mTc sodium pertechnetate, previously reduced with and acid solution of tin chloride at different concentrations (0.003, 0.005, 0.007, 0.01, 0.05 and 0.1 mg/ml) and at different times (5, 10, 15, 30 and 60 min) and temperatures (room temperature, 40 °C and 60 °C). Radiolabelling with ⁶⁷Ga was performed by incubation of the nanoparticles with 37 MBq of ⁶⁷gallium chloride (obtained from commercial gallium-⁶⁷citrate) at different times (10 and 30 min) and temperatures (room temperature, 30 °C and 60 °C), and posterior purification with microconcentrators. The radiochemical purity was evaluated by TLC. Stability studies of radiolabeled nanoparticles in physiological serum and blood plasma were performed. Biodistribution studies of nanoparticles coated with GPM2 polymer were carried out in Wistar rats after intravenous administration of the nanoparticles. Control animals were carried out with 99mTc sodium pertechnetate and ⁶⁷Ga chloride. To do so, the animals were killed and activity in organs was measured in a gamma counter.
Results
99mTc labeling was carried out optimally with a tin concentration of 0.007 mg/ml for the GPM2 nanoparticles and 0.005 mg/ml for the rest of the formulations, with a radiolabelling time of 10 min at room temperature. In the case of ⁶⁷Ga the label was optimized at 30 °C temperature and 30 min of incubation. In both cases the radiochemical purity obtained was greater than 97%. The nanoparticles showed high stability in vitro after 48 h of labeling (70% nanoparticles labeled with 99mTc and 90% those labeled with ⁶⁷Ga). Biodistribution studies of nanoparticles 99mTc-GPM2 and ⁶⁷Ga-NOTA-GPM2 showed a high accumulation of activity in the liver at 2 and 24 h after intravenous administration.
Conclusion
The labeling procedure with 99mTc and ⁶⁷Ga of albumin and albumin modified with NOTA nanoparticles allows obtaining nanoparticles with high labeling yields and adequate in vitro stability, allowing their use for in vivo studies.
Nanomaterial-based wound healing has tremendous potential for treating and preventing wound infections with its multiple benefits compared with traditional treatment approaches. In this regard, the physiochemical properties of nanomaterials enable researchers to conduct extensive studies on wound-healing applications. Nonetheless, issues concerning the use of nanomaterials in accelerating the efficacy of existing medical treatments remain unresolved. The present review highlights novel approaches focusing on the recent innovative strategies for wound healing and infection controls based on nanomaterials, including nanoparticles, nanocomposites, and scaffolds, which are elucidated in detail. In addition, the efficacy of nanomaterials as carriers for therapeutic agents associated with wound-healing applications has been addressed. Finally, nanomaterial-based scaffolds and their premise for future studies have been described. We believe that the in-depth analytical review, future insights, and potential challenges described herein will provide researchers an up-to-date reference on the use of nanomedicine and its innovative approaches that can enhance wound-healing applications.
Resumen
Objetivo
Optimizar el radiomarcaje con 99mTc y ⁶⁷Ga de nanopartículas de albúmina recubiertas con 4 polímeros sintéticos distintos y evaluar su estabilidad in vivo e in vitro, así como su biodistribución in vivo tras su administración intravenosa.
Material y métodos
Las nanopartículas se prepararon empleando albúmina y albúmina modificada con NOTA mediante el método de desolvatación y se recubrieron con 4 polímeros distintos; HPMC, GMN2, GPM2 y GTM2. Se purificaron, liofilizaron y caracterizaron. El marcaje con 99mTc se realizó con 74 MBq de pertecnetato [99mTc] sódico previamente reducido con una disolución ácida de cloruro de estaño a diferentes concentraciones (0,003; 0,005; 0,007; 0,01; 0,05 y 0,1 mg/ml), a distintos tiempos (5, 10, 15, 30 y 60 min) y temperaturas (temperatura ambiente, 40 °C y 60 °C). El marcaje con ⁶⁷Ga se llevó a cabo mediante incubación de las nanopartículas con 37 MBq de cloruro de ⁶⁷Ga (obtenido a partir de citrato de ⁶⁷Ga comercial) a distintos tiempos (10 y 30 min) y temperaturas (temperatura ambiente, 30 °C y 60 °C) y posterior purificación con microconcentradores. La pureza radioquímica de ambos marcajes se evaluó mediante TLC. Se llevaron a cabo estudios de estabilidad de las nanopartículas marcadas en suero fisiológico y plasma sanguíneo. Los estudios de biodistribución de las nanopartículas recubiertas con el polímero GPM2 se llevaron a cabo en ratas Wistar tras la administración intravenosa de las nanopartículas. Se realizaron animales control con pertecnetato [99mTc] sódico y cloruro de ⁶⁷Ga. Posteriormente, los animales fueron sacrificados y se midió la actividad de los órganos en un contador gamma.
Resultados
El marcaje con 99mTc se llevó a cabo de forma óptima con una concentración de estaño de 0,007 mg/ml para las nanopartículas GPM2 y de 0,005 mg/ml para el resto de formulaciones, con un tiempo de marcaje de 10 min y a temperatura ambiente. En el caso del ⁶⁷Ga el marcaje se optimizó a 30 °C de temperatura y 30 min de incubación. En ambos casos, la pureza radioquímica obtenida fue superior al 97%. Las nanopartículas presentaron una elevada estabilidad in vitro pasadas las 48 h del marcaje (70% las nanopartículas marcadas con 99mTc y 90% las marcadas con ⁶⁷Ga). Los estudios de biodistribución de las nanopartículas [99mTc]-GPM2 y [⁶⁷Ga]-NOTA-GPM2 mostraron una elevada acumulación de actividad en el hígado tanto a las 2 h como a las 24 h de la administración intravenosa.
Conclusión
El procedimiento de marcaje con 99mTc y ⁶⁷Ga de nanopartículas de albúmina y albúmina modificada con NOTA permite la obtención de nanopartículas con elevados rendimientos de marcaje y una adecuada estabilidad in vitro, permitiendo su utilización para la realización de estudios in vivo.
The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in regenerative medicine. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. While clinically, adipose-derived stem cells (ADSCs) are one of the most widely used types of stem cells used more than five years in clinically setting. It has many advantages including; yields a high number of ADSCs per volume of tissue, high rate of proliferation, anti-fibrotic, anti-apoptotic, anti-inflammation, immunomodulation, and paracrine mechanisms have been demonstrated in various preclinical studies. It is much easier to harvest compared with bone marrow stem cells. Results of clinical studies have demonstrated the potentials of ADSCs for stem cells therapy for a number of clinical disorders. The aim of this paper was to provide an update on the most recent developments of ADSCs, by highlighting the properties and features of ADSCs, critically discussing its clinical benefit and its clinical trials in treatment and regeneration. This is a multi-billion dollars industry with huge interest to clinician, academia and industries.
The clinical challenge that research on antibacterial coatings faces nowadays is the need of reduction of resistant bacterial infections, major source of implant rejection and repeated surgery.
In order to avoid microorganisms attachment and biofilm formation, coating materials on medical devices have been developed with shortcomings represented by short-term durability and induction of new mechanisms of bacterial resistance.
Graphene-based films and hydrogel could represent the next generation protective coatings due to their excellent mechanical, chemical and thermal properties, high nanoparticle adsorption and antibacterial action. In this short commentary, we will report the recent developments of graphene oxide based coatings. Graphene oxide is a water-soluble derivative of graphene that allows high drug loading and miscibility with polymers, making it mouldable in any desired shape. Recent applications in wound healing and tissue engineering will be discussed as well as critical issues prior to clinical use of graphene oxide coatings.
Graphene oxide (GO) consisting of a carbon monolayer has been widely investigated for tissue engineering platforms because of its unique properties. For this study, we fabricated a GO-applied scaffold and assessed the cellular and tissue behaviors in the scaffold. A preclinical test was conducted to ascertain whether the GO scaffold promoted bone induction in dog tooth extraction sockets. For this study, GO scaffolds were prepared by coating the surface of a collagen sponge scaffold with 0.1 and 1 µg/mL GO dispersion. Scaffolds were characterized using scanning electron microscopy (SEM), physical testing, cell seeding, and rat subcutaneous implant testing. Then a GO scaffold was implanted into a dog tooth extraction socket. Histological observations were made at 2 weeks postsurgery. SEM observations show that GO attached to the surface of collagen scaffold struts. The GO scaffold exhibited an interconnected structure resembling that of control subjects. GO application improved the physical strength, enzyme resistance, and adsorption of calcium and proteins. Cytocompatibility tests showed that GO application significantly increased osteoblastic MC3T3-E1 cell proliferation. In addition, an assessment of rat subcutaneous tissue response revealed that implantation of 1 µg/mL GO scaffold stimulated cellular ingrowth behavior, suggesting that the GO scaffold exhibited good biocompatibility. The tissue ingrowth area and DNA contents of 1 µg/mL GO scaffold were, respectively, approximately 2.5-fold and 1.4-fold greater than those of the control. Particularly, the infiltration of ED2-positive (M2) macrophages and blood vessels were prominent in the GO scaffold. Dog bone-formation tests showed that 1 µg/mL GO scaffold implantation enhanced bone formation. New bone formation following GO scaffold implantation was enhanced fivefold compared to that in control subjects. These results suggest that GO was biocompatible and had high bone-formation capability for the scaffold. The GO scaffold is expected to be beneficial for bone tissue engineering therapy.
Type I, bovine skin collagen was allowed to gel in the presence of various concentrations of a carbon nanotube material covered with a polystyrene/polyaniline copolymer, called a carbon nanobrush (CNB). The rate of collagen gelation was enhanced by the presence of the CNB in a dose dependent manner. The extent of collagen gelation was due to the concentration of collagen and not the amount of CNB. Collagen D-periodicity, and average fibril diameter were unchanged by the CNB material as seen in transmission electron micrographs. Gel tensile strength was reduced by the presence of the CNB in a dose related manner. The collagen-CNB mixture may have a role in the repair and reconstruction of wounds or degenerated connective tissue.
Silver sulfadiazine (SSD) has been the standard topical antimicrobial for burn wounds for decades. Recently, nanometer-sized silver particles are available which have high surface to volume ratio and remain effective even at a very low concentration and minimizes the chance for tissue toxicity due to silver. Hence, we conducted a randomized controlled trial to compare the effectiveness of topical SSD and nano-crystalline silver (AgNP) hydrogel in burn wounds management.
Study was conducted in the Burn Unit of IPGME&R & SSKM Hospital Calcutta, from January 2011 to August 2012. Patients with 2° burn injury were randomly allocated to SSD and AgNP treatment group. Clinical assessments of burn wound were done on every week till 4(th) week and on completion of treatment.
Data for evaluation were obtained for 54 patients on SSD (2° deep-dermal cases 27) and 52 (2° deep-dermal cases 31) on AgNP treatment. Healing status of 2° deep-dermal burns was more satisfactory for AgNP group than SSD treatment at 4 weeks. Among patients receiving AgNP, 80.6% showed at least 50% healing of 2° deep-dermal wounds compared to 48.1% on SSD at 4 weeks (P = 0.001). The figures for complete healing at 4 weeks were, respectively, 4% and 0% (P = 0.116).
AgNP can be an effective and superior alternative to SSD for burn wounds, particularly 2° deep-dermal burns. Healing can be expected, in general, in 6 to 8 weeks time, depending upon the extent of body surface involvement.
Ocular surface is the outermost part of the visual system that faces many extrinsic or intrinsic threats, such as chemical burn, infectious pathogens, thermal injury, Stevens-Johnson syndrome, ocular pemphegoid, and other autoimmune diseases. The cornea plays an important role in conducting light into the eyes and protecting intraocular structures. Several ocular surface diseases will lead to the neovascularization or conjunctivalization of corneal epithelium, leaving opacified optical media. It is believed that some corneal limbal cells may present stem cells-like properties and are capable of regenerating corneal epithelium. Therefore, cultivation of limbal cells and reconstruction of ocular surface with these limbal cells grafts have attracted tremendous interests in the past few years. Currently, stem cells are found to potentiate regeneration medicine by their capability of differentiation into multiple lineage cells. While, embryonic, adult, and induced stem cells are commonly considered as the cell sources for clinical use. Different stem cells have varied specific advantages and limitations for in vivo and in vitro expansion. Other than ocular surface diseases, culture and transplantation of corneal endothelial cells is another major issue for corneal decompensation and awaits further studies to find out comprehensive solutions dealing with non-regenerative corneal endothelium. Recently, studies of in-vitro endothelium culture and rho-associated kinase (ROCK) inhibitor gain much encouraging results. Some clinical trials have already been finished and achieved remarkable vision recovery. Finally, nanotechnology has shown great improvement in ocular drug delivery systems during past two decades. Strategies to reconstruct ocular surface could combine with nanoparticles to facilitate wound healing, drug delivery, and even neovascularization inhibition. In this review article, we summarized the major advances of corneal limbal stem cells, limbal stem cell deficiency, corneal endothelial cell culture/transplantation and application of nanotechnology on ocular surface reconstruction. We elucidated potential applications that covered by current knowledge for future treatment of corneal diseases.
Repair of deep wounds by cell transplantation strongly depends on angiogenesis and on the regeneration of skin and appendages. In this study, plasmid DNA encoding vascular endothelial growth factor-165 (VEGF-165) was transduced into bone-marrow mesenchymal stem cells (MSCs) using a
nonviral vector, β-cyclodextrin-linked polyethylenimine, to enhance angiogenic capacity. The effects of MSCs administered by intradermal injection or transplantation on wound closure were compared in a full-thickness excision wound model. The results showed that the MSC-seeded
sponge had significantly stronger acceleration in wound closure than the MSC injection. The effects on wound repair and regeneration of transplanted MSCs and pDNA-VEGF165-transfected MSCs (TMSCs) with gelatin/β-tricalcium phosphate scaffold were also investigated. Compared with
MSC transplantation, TMSC transplantation showed higher efficacy in stimulating wound closure, promoting dermal collagen synthesis and regulating the deposition of newly formed collagen. In addition, the angiogenic capacity of the TMSCs was higher than that of the MSCs. The results indicate
that the nonviral genetic engineering of the MSCs is a promising strategy to enhance the angiogenic capacity of MSCs for wound repair and angiogenesis. Functional gene-activated MSCs may be used as cost-effective and accessible seed cells for skin tissue engineering and as novel carriers for
wound gene therapy.
Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing, angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, higher re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on E. coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles.
Background
Excessive expression of matrix metalloproteinase-9 (MMP-9) is deleterious to the cutaneous wound-healing process in the context of diabetes. The aim of the present study was to explore whether a cationic star-shaped polymer consisting of β-cyclodextrin (β-CD) core and poly(amidoamine) dendron arms (β-CD-[D3]7) could be used as the gene carrier of small interfering RNA (siRNA) to reduce MMP-9 expression for enhanced diabetic wound healing.
Methods
The cytotoxicity of β-CD-(D3)7 was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MMT) method in the rat CRL1213 skin fibroblast cell line. The transfection efficiency of β-CD-(D3)7/MMP-9-small interfering RNA (siRNA) complexes was determined by confocal microscopy and flow cytometry. Quantitative real time (RT) polymerase chain reaction was performed to measure the gene expression of MMP-9 after the transfection by β-CD-(D3)7/MMP-9-siRNA complexes. The β-CD-(D3)7/MMP-9-siRNA complexes were injected on the wounds of streptozocin-induced diabetic rats. Wound closure was measured on days 4 and 7 post-wounding.
Results
β-CD-(D3)7 exhibited low cytotoxicity in fibroblast cells, and easily formed the complexes with MMP-9-siRNA. The β-CD-(D3)7/MMP-9-siRNA complexes were readily taken up by fibroblast cells, resulting in the downregulation of MMP-9 gene expression (P<0.01). Animal experiments revealed that the treatment by β-CD-(D3)7/MMP-9-siRNA complexes enhanced wound closure in diabetic rats on day 7 post-wounding (P<0.05).
Conclusion
β-CD-(D3)7 may be used as an efficient carrier for the delivery of MMP-9-siRNA to reduce MMP-9 expression in skin fibroblast cells and promote wound healing in diabetic rats.
Silver nanoparticles (Ag NPs) have been widely used in bone grafts due to their antimicrobial/antiviral properties. Despite extensive research focused on the cytotoxicity and genotoxicity of Ag NPs, little is known of their effect on cell differentiation. In this study, the uptake of Ag NPs and its effect on the osteogenic differentiation of human mensenchymal stem cells (hMSCs) were investigated in vitro. Ag NPs with a diameter of -30 nm were prepared. The hMSCs were exposed to different concentrations of Ag NPs, i.e., 0, 10, 50 and 100 microg/mL. The results show that Ag NPs cause cytotoxicity of hMSCs. It is also demonstrated that the uptake of Ag NPs does not affect the alkaline phosphatase activity, osteocalcin gene expression, osteopontin expression and mineralization level of hMSCs. The uptake of Ag NPs does not influence the osteogenic differentiation of hMSCs. This will give a positive reference for the application of Ag NPs in bone tissue engineering, especially their incorporation with stem cells in bone grafts.
The management of difficult to heal wounds can considerably reduce the time required for tissue repairing and promote the healing process, minimizing the risk of infection. Silver compounds, especially silver sulfadiazine (AgSD), are often used to prevent or to treat wound colonization, also in presence of antibiotic-resistant bacteria. However, AgSD has been shown to be cytotoxic in vitro toward fibroblasts and keratinocytes and consequently to retard wound healing in vivo. Recently, platelet lysate (PL) has been proposed in clinical practice for the healing of persistent lesions. The aim of the present work was the development of wound dressings based on AgSD loaded in solid lipid nanoparticles (SLNs), to be used in association with PL for the treatment for skin lesions. SLN were based on chondroitin sulfate and sodium hyaluronate, bioactive polymers characterized by well-known tissue repairing properties. The encapsulation of AgSD in SLN aimed at preventing the cytotoxic effect of the drug on normal human dermal fibroblasts (NHDFs) and at enabling the association of the drug with PL. SLN were loaded in wound dressings based on hydroxypropylmethyl cellulose (HPMC) or chitosan glutamate (CS glu). These polymers were chosen to obtain a sponge matrix with suitable elasticity and softness and, moreover, with good bioadhesive behavior on skin lesions. Dressings based on chitosan glutamate showed antimicrobial activity with and without PL. Even though further in vivo evaluation could be envisaged, chitosan based dressings demonstrated to be a suitable prototype for the treatment for skin lesions.
Wound healing is a complex process involving many interdependent and overlapping sequences of physiological actions. The application of exogenous lactate released from poly (lactic-co-glycolic acid) (PLGA) polymer accelerated angiogenesis and wound healing processes. Curcumin is a well-known topical wound healing agent for both normal and diabetic-impaired wounds. Hence, we hypothesized that the PLGA nanoparticles encapsulating curcumin could much potentially accelerate the wound healing. In a full thickness excisional wound healing mouse model, PLGA-curcumin nanoparticles showed a twofold higher wound healing activity compared to that of PLGA or curcumin. Histology and RT-PCR studies confirmed that PLGA- curcumin nanoparticles exhibited higher re-epithelialization, granulation tissue formation and anti-inflammatory potential. PLGA nanoparticles offered various benefits for the encapsulated curcumin like protection from light degradation, enhanced water solubility and showed a sustained release of curcumin over a period of 8 days. In conclusion, we demonstrated the additive effect of lactic acid from PLGA and encapsulated curcumin for the active healing of wounds.
Rapid development of nanotechnologies and their applications in clinical research have raised concerns about the adverse effects of nanoparticles (NPs) on human health and environment. NPs can be directly taken up by organs exposed, but also translocated to secondary organs, such as the central nervous system (CNS) after systemic- or subcutaneous administration, or via the olfactory system. The CNS is particularly vulnerable during development and recent reports describe transport of NPs across the placenta and even into brain tissue using in vitro and in vivo experimental systems. Here, we investigated whether well-characterized commercial 20 and 80 nm Au- and AgNPs have an effect on human embryonic neural precursor cell (HNPC) growth. After two weeks of NP exposure, uptake of NPs, morphological features and the amount of viable and dead cells, proliferative cells (Ki67 immunostaining) and apoptotic cells (TUNEL assay), respectively, were studied. We demonstrate uptake of both 20 and 80 nm Au- and AgNPs respectively, by HNPCs during proliferation. A significant effect on the sphere size- and morphology was found for all cultures exposed to Au- and AgNPs. AgNPs of both sizes caused a significant increase in numbers of proliferating and apoptotic HNPCs. In contrast, only the highest dose of 20 nm AuNPs significantly affected proliferation, whereas no effect was seen on apoptotic cell death. Our data demonstrates that both Au- and AgNPs interfere with the growth profile of HNPCs, indicating the need of further detailed studies on the adverse effects of NPs on the developing CNS.
This study aims to investigate the novel preparation of solid lipid nanoparticle-enriched hydrogel (SLN-gel) for the topical delivery of astragaloside IV and to determine the effects of astragaloside IV-based SLN-gel on wound healing and anti-scar formation. Solid lipid nanoparticles (SLNs) were prepared through the solvent evaporation method. The particle size, polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), drug release, and morphological properties of the SLNs were characterized. The optimized SLNs were incorporated in carbomer hydrogel to form an SLN-enriched gel (SLN-gel) carrier. The effects of astragaloside IV-enriched SLNs on wound healing were determined using the wound scratch test, and their uptake by skin cells was tested in vitro. With the rat full-skin excision model, the in vivo regulation of astragaloside IV-based SLN-gel in the wound stages of re-epithelization, angiogenesis, and extracellular matrix remodeling was investigated. The best formulation of astragaloside IV-based SLNs had high EE (93%±5%) and ZP (-23.6mV±1.5mV), with a PDI of 0.18±0.03 and a drug loading percentage of 9%. Astragaloside IV-based SLNs and SLN-gel could release drug sustainably. Astragaloside IV-based SLNs enhanced the migration and proliferation of keratinocytes and increased drug uptake on fibroblasts in vitro (P<0.01) through the caveolae endocytosis pathway, which was inhibited by methyl-β-cyclodextrin. Astragaloside IV-based SLN-gel strengthened wound healing and inhibited scar formation in vivo by increasing wound closure rate (P<0.05) and by contributing to angiogenesis and collagen regular organization. SLN-enriched gel is a promising topical drug delivery system. Astragaloside IV-loaded SLN-enriched gel was proven as an excellent topical preparation with wound healing and anti-scar effects.
During the last decade, due to advances in functionalization chemistry, novel nanobiomaterials with applications in tissue engineering and regenerative medicine have been developed. These novel materials with their unique physical and chemical properties are bioactive hierarchical structures that hold great promise for future development of human tissues. Thus, various nanomaterials are currently being intensively explored in the directed differentiation of stem cells, the design of novel bioactive scaffolds, and new research avenues towards tissue regeneration. This paper illustrates the latest achievements in the applications of nanotechnology in tissue engineering in the field of regenerative medicine.
The purpose of this study was to further investigate that phenomenon and to explore the effect silver sulfadiazine on wound healing. Full-thickness burn wounds were created on the dorsum of Wistar albino rats under anesthesia. The wounds were treated with silver sulfadiazine and saline-soaked dressing for fourteen days, and then observed until healed. Wound surface area was measured each three days. Time to 50% and 90% healing was compared. No clinical infections occurred. Wound half-life and healing times were shortest in the saline-soaked group (P < 0.0001) in full-thickness burns. Wound contraction was delayed by silver sulfadiazine. These data suggest that silver sulfadiazine retard burn wound healing. Infection control without delay of burn wound healing is most appealing and clinical trials are planned.
Background
The therapeutic strategies for malignant melanoma are still cancer chemotherapy, radiotherapy, and tumor resection. However, these therapeutic strategies often lead to a reduced neutrophilic granulocyte count or loss of more blood after surgical tumor resection. In this study, we developed a formulation of hemostatic gauze impregnated with sustained-release granulocyte colony-stimulating factor (G-CSF) with increasing of the neutrophilic granulocyte count in the blood following chemotherapy and decreasing blood loss after surgical tumor resection.
Methods
We designed a formulation with both hemostatic properties and increased neutrophil content to be used in cancer chemotherapy, radiotherapy, and tumor resection, comprising a hemostatic gauze as a scaffold and (G-CSF)-loaded dextran nanoparticles coated with polylactic-co- glycolic acid (PLGA) solution fabricated by direct spray-painting onto the scaffold and then vacuum-dried at room temperature. The performance of this system was evaluated in vitro and in vivo.
Results
Nearly zero-order release of G-CSF was recorded for 12–14 days, and the cumulative release of G-CSF retained over 90% of its bioactivity in a NFS-60 cell line proliferation assay when the scaffold was incubated in phosphate-buffered saline (pH 7.4) at 37°C. The in vivo hemostatic efficacy of this formulation was greater than that of native G-CSF, the scaffold directly spray-painted with G-CSF solution or PLGA organic solution as a coating, or when a blank scaffold was covered with the coating.
Conclusion
Our results suggest that this formulation has both hemostatic properties and increased neutrophil activity.
Astragaloside IV is the chief ingredient of Radix Astragali, which has been used in the Traditional Chinese Medicine as a major component of many polyherbal formulations for the repair and regeneration of injured organ and tissues. This study is to investigate the influence of astragaloside IV on both of the wound healing and scar formation.
For the in vitro evaluation, the influence of the astragaloside IV in the wound scratch test of keratinocytes and the secretion of transforming growth factor-β1, a key factor contributing to scar formation were determined. With the rat skin excision model, the in vivo regulation of astragaloside IV on wound closure, angiogenesis and collagen disposition were also evaluated.
Astragaloside IV was shown to significantly promote the migration of keratinocytes in wound scratching assay. The superior effect of Astragaloside IV was observed at 100 μmol/L, in which the recover rates was increased with 2 and 3 folds after 48 h and 96 h respectively than that of blank control (P<0.01). Animal skin closure measurement showed that astragaloside IV could stimulate the wound healing, e.g. with 21% recover in contrast to the 8% of blank control at the 6th day. Biomechanic and Masson's trichrome stain analysis indicated that astragaloside IV may improve the strength of the repaired skin and promoted the angiogenesis and collagen synthesis. Meanwhile, the picrosirius-sirus red stain and Elisa test definitely showed the anti-scar effects of astragaloside IV by decreasing the levels of collagen I/III and TGF-β1 secretion by firbroblasts with a dose-dependent manner (25-100 μmol/L).
Astragaloside IV was shown a promising natural product with both healing and anti-scar effects for wound treatment. These results give the evidence for the application of astragaloside IV in the treatment of injury.
Collagen-chitosan composite film modified with grapheme oxide (GO) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC), termed CC-G-E film, was loaded with basic fibroblast growth factor (bFGF) as the development of an efficacious wound healing device. In this study we report a novel drug delivery system that prevents the initial burst release and loss of bioactivity of drugs in vitro and in vivo applications. The results showed that CC-G-E film possessed improved thermal stability and a higher rate of crosslinking with increased mechanical properties when the dosage of GO was between 0.03% and 0.07%. It was shown that the in vitro release of bFGF from CC-G-E film continued for more than 28d. Furthermore, the CC-G-E films demonstrated excellent in vitro biocompatibility following culture with L929 fibroblasts in terms of cell adhesion and proliferation. CC-G-E films were implanted into Sprague-Dawley rats to characterize their ability to repair full-thickness skin wounds. Results showed that the CC-G-E film accelerated the wound healing process compared with the blank control. Based on all the results, it was concluded that CC-G-E film operates as a novel drug delivery system and due to its performance in wound remodeling, has potential to be developed as a wound dressing material.
Polysaccharide hydrogels have been widely used as biomaterials in biomedical field. In this article, composite hydrogels were prepared through the Schiff-base reaction between the aldehyde of oxidized konjac glucomannan (OKGM) and the amino of carboxymethyl chitosan (CMCS). Meanwhile, different amount of graphene oxide (GO) was added as nano-additive. The hydrogels have been characterized by various methods including Fourier transform infrared spectroscopy (FT-IR) and Surface morphology (SEM). Through the observation of SEM, the hydrogels’ scaffolds present a homogeneous interconnected pore structure after lyophilizing. In addition, the influence of different GO content on properties including gelation time, swelling ability, water evaporation rate and mechanical properties were investigated. The results indicate that the hydrogels have short gelation time, appropriate swelling ability and water evaporation rate. Especially, the compressive strength and modulus increase 144% and 296% respectively as the GO content increase from 0 to 5 mg/ml. Moreover, MTT assay was applied to evaluate the biocompatibility of hydrogels. The result indicate that hydrogels with GO show better biocompatibility. Therefore, due to the appropriate water absorption capacity, the similar compressive modulus with soft tissue and excellent biocompatibility, the composite hydrogels have potential application in wound dressings.
Recent years, researchers have proven the release of silver ions (Ag+) from the silver nanoparticles (Ag NPs) significantly affects their toxicity to bacteria and other organisms. Due to the difficulty in maintaining a steady flux of high concentration of Ag+, it's still challenging to develop a highly efficient, stable and biocompatible Ag NPs based antimicrobial material. To circumvent this issue, we developed a new Ag-based bactericide through the fabrication of sunlight-driven and ultrafine silver/silver chloride anchored on reduced graphene oxide (Ag/AgCl/rGO). This stable Ag/AgCl nanophotocatalyst with negligible releasing of Ag+ generated high amount of oxidative radicals, killing the bacteria, thus achieved both high bactericidal efficiency and stability. Moreover, functionalization of the nanomaterial with PDDA has highly adsorptive capacity, which can capture the bacteria and possibly enhance the bactericidal activity. In vivo histopathological study results showed that the Ag/AgCl/rGO nanomaterial could obviously promote regenerated epidermis formation of mice burned wound, which showed the good biomedical potential of Ag/AgCl/rGO nanomaterial in burn wound healing.
The regeneration of functional skin remains elusive, due to poor engraftment, deficient vascularization, and excessive scar formation. Aiming to overcome these issues, the present study proposed the combination of a three-dimensional graphene foam (GF) scaffold loaded with bone marrow derived mesenchymal stem cells (MSCs) to improve skin wound healing. The GFs demonstrated good biocompatibility and promoted the growth and proliferation of MSCs. Meanwhile, the GFs loaded with MSCs obviously facilitated wound closure in animal model. The dermis formed in the presence of the GF structure loaded with MSCs was thicker and possessed a more complex structure at day 14 post-surgery. The transplanted MSCs correlated with upregulation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which may lead to neo-vascularization. Additionally, an anti-scarring effect was observed in the presence of the 3D-GF scaffold and MSCs, as evidenced by a downregulation of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) together with an increase of TGF-β3. Altogether, the GF scaffold could guide the wound healing process with reduced scarring, and the MSCs were crucial to enhance vascularization and provided a better quality neo-skin. The GF scaffold loaded with MSCs possesses necessary bioactive cues to improve wound healing with reduced scarring, which may be of great clinical significance for skin wound healing.
Complex spatiotemporal interaction of Rho GTPases with microtubules (MTs) and MT-associated proteins drives directed cellular migration. In this issue, Charafeddine et al. describe a role for a novel MT-severing enzyme, fidgetin-like 2 (FL2), in directional migration of keratinocytes and fibroblasts. FL2 normally localizes to the leading edge of the cell cortex where it shears MTs, thus dictating the size and distribution of focal adhesions by regulating cytoskeletal remodeling. Small interfering RNA (siRNA)-directed knockdown of FL2 increases cell migration and focal adhesion area in vitro through possible interaction with Rho GTPases. Efficient FL2 knockdown in murine wounds was achieved using nanoparticles as a siRNA delivery vehicle, and this resulted in enhanced wound closure in vivo. Effective siRNA nanoparticle targeting of MT-severing enzymes offers promise of controlled and targeted delivery that may maximize therapeutic success for patients with burn wounds and chronic wound disorders.
The objective of this study was to investigate whether surface coating with graphene could enhance the surface bioactivation of PET-based artificial ligaments to accelerate graft-to-bone healing after ACL reconstruction. In an in vitro study, the proliferation of MC3T3-E1 cells and their differentiation on the scaffolds were quantified via MTT and RT-PCR assays. The significantly higher optical-density values and transcription levels of osteoblast-specific genes indicated that graphene modification could promote the proliferation of MC3T3-E1 and accelerate their specific differentiation into osteogenic lineages on scaffolds. In an in vivo test, rabbits were used to establish an extra-articular graft-to-bone healing model. At 4, 8 and 12 weeks after surgery, biomechanical tests, micro-computed tomography (CT) analysis and histological observations were performed. The final results demonstrated that the microstructural parameters, the average mineral apposition rate (MAR) of the bone and the biomechanical properties of the graphene-coated PET-AL (G-PET-AL) group were significantly higher than those of the PET-AL graft group (P<0.05). The results of Van Gieson (VG) staining indicated that in the G-PET-AL group, there was more newly formed bone than there was in the group in which non-graphene-coated PET artificial ligaments were used. In conclusion, graphene exhibits considerable potential for enhancing the surface bioactivation of materials.
Angiogenesis, a process resulting in the formation of new capillaries from the pre-existing vasculature plays vital role for the development of therapeutic approaches for cancer, atherosclerosis, wound healing, and cardiovascular diseases. In this report, the synthesis, characterization, and angiogenic properties of graphene oxide (GO) and reduced graphene oxide (rGO) have been demonstrated, observed through several in vitro and in vivo angiogenesis assays. The results here demonstrate that the intracellular formation of reactive oxygen species and reactive nitrogen species as well as activation of phospho-eNOS and phospho-Akt might be the plausible mechanisms for GO and rGO induced angiogenesis. The results altogether suggest the possibilities for the development of alternative angiogenic therapeutic approach for the treatment of cardiovascular related diseases where angiogenesis plays a significant role.
This research addresses the development and in vitro evaluation of lipid nanoparticle (NP)-based dressings to optimize the delivery of human recombinant epidermal growth factor (rhEGF) for the topical treatment of chronic wounds. The systems investigated were rhEGF-loaded solid lipid nanoparticles (rhEGF-SLN) and rhEGF-loaded nanostructured lipid carriers (rhEGF-NLC) formulated in wound dressings comprising either semi-solid hydrogels or fibrin-based solid scaffolds. Following detailed characterisation of the NP, in vitro diffusion cell experiments (coupled with dermatopharmacokinetic measurements), together with confocal microscopic imaging, conducted on both intact skin samples, and those from which the barrier (the stratum corneum) had been removed, revealed that (a) the particles remained essentially superficially located for at least up to 48hours post-application, (b) rhEGF released on the surface of intact skin was unable to penetrate to the deeper, viable layers, and (c) sustained release of growth factor from the NP "drug reservoirs" into barrier-compromised skin was observed. There were no significant differences between the in vitro performance of rhEGF-SLN and rhEGF-NLC, irrespective of the formulation employed. It is concluded that, because of their potentially longer-term stability, the fibrin-based scaffolds may be the most suitable approach to formulate rhEGF-loaded lipid nanoparticles.
Copyright © 2015. Published by Elsevier B.V.
Silver-containing dressings are commonly used on healing wounds, including diabetic ulcers. Some studies have shown that dress¬ing materials with silver have negative effects on wound healing, spe¬cifically, that the wound healing process is inhibited by deposited silver. Therefore, the authors treated wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) in Sprague-Dawley (SD) rats and strep¬tozotocin (STZ)-induced diabetic rats with silver dressings to evaluate the risks of silver.
The study used 54 SD rats and 54 STZ-induced diabetic rats. Full-thickness skin defects were cre¬ated in all animals and then infected with MRSA. The rats were divided into 6 groups according to the dressing materials: nanocrystalline sil¬ver (Ac) (ACTICOAT, Smith and Nephew Healthcare, Hull, UK), silver carboxymethylcellulose (Aq) (AQUACEL Ag, ConvaTec, Bristol-Myers Squibb, Skillman, NJ), silver sulfadiazine (M) (Medifoam Silver, Biopol Global Co, Ltd, Seoul, Korea), nanocrystalline silver (P) (PolyMem Silver, Ferris Mfg Corp, Fort Worth, TX), Ilvadon cream (I) (Ildong Pharaceuti¬cal Co, Ltd, Seoul, Korea), and 10% povidone iodine (B) (Betadine, Sung Kwang Pharmaceutical Co Ltd, Gyeonggi-Do, Korea) as a control agent. Blood was collected from all animals to measure the hematologi¬cal effects. The skin, spleen, liver, and kidneys of each rat were biopsied and used to make paraffin sections in which the silver deposition was measured using energy-dispersive spectrometry (EDS).
Fifteen days after wounding, only the Ac, P, and I groups differed significantly (P < 0.05) from the B group. The glutamic-oxaloacetic transaminase, blood urea nitrogen, and alkaline phosphatase levels differed signifi¬cantly (P < 0.05) between the SD and STZ rats. No silver deposition was found in any organ.
The silver dressings induced slight liver damage in the STZ-rats. Although changes in serum chemistry caused by silver were seen, this did not indicate silver deposition in the organ as the EDS did not show excess levels. The risk of silver deposition appears to be low. The hazards of silver-containing dressing products in MRSA-infected wounds were insignificant.
Background:
Atheroregression becomes an attractive target for cardiovascular treatment. Some clinical trials have demonstrated that intensive therapy with rosuvastatin or recombinant ApoA-I Milano can partially reduce the total atheroma volume (TAV) up to 6.38 mm(3) or 14.1 mm(3) respectively. Our previous bench studies of selected nanotechnologies documented TAV reduction up to an unprecedented 79.4 mm(3).
Methods:
The completed observational three arms (n = 180) first-in-man trial (the NANOM FIM trial) assessed (NCT01270139) the safety and feasibility of two delivery techniques for nanoparticles (NP), and plasmonic photothermal therapy (PPTT). Patients were assigned to receive either (1) nano-intervention with delivery of silica-gold NP in a bioengineered on-artery patch (n = 60), or (2) nano-intervention with delivery of silica-gold iron-bearing NP with targeted micro-bubbles and stem cells using a magnetic navigation system (n = 60) versus (3) stent implantation (n = 60). The primary outcome was TAV at 12 months.
Results:
The mean TAV reduction at 12 months in the Nano group was 60.3 mm(3) (SD 39.5; min 41.9 mm(3), max 94.2 mm(3); p < 0.05) up to mean 37.8% (95% CI: 31.1%, 51.7%; p < 0.05) plaque burden. The analysis of the event free survival of the ongoing clinical follow-up shows the significantly lower risk of cardiovascular death in the Nano group when compared with others (91.7% vs. 81.7% and 80% respectively; p < 0.05) with no cases of the target lesion-related complications.
Conclusions:
PPTT using silica-gold NP associated with significant regression of coronary atherosclerosis.
Recently gold nanomaterials have been widely applied in the biomedical field, but their biosafety is still controversial. We immobilized small gold nanoparticles (AuNPs) on a large silica substrate to form silica-gold core-shell materials (SiO2@AuNPs) via classical seed-mediated growth. In vitro, 500nm-SiO2@AuNPs could promote the proliferation of mouse embryonic fibroblast cells (NIH/3T3). The results of transmission electron microscope (TEM) showed that the vast majority of particles did not enter cells and that the morphology of microtubules experienced no change as observed in the confocal microscope images. The mechanism may be that the large silica substrate kept AuNPs outside the cells and the nano-size concavo-convex gold shell facilitated to cell adhesion, resulting in the proliferation. In vivo, a cutaneous full-thickness excisional wound rat model was applied to assess the healing efficiency of 500nm-SiO2@AuNPs. The results indicated that SiO2@AuNPs could promote wound healing, which was potentially related to the anti-inflammatory and antioxidation of AuNPs. The pathological finding showed that the healing levels of SiO2@AuNPs were significantly better than those of the control groups. Our study may provide insight into the application of silica-gold core-shell materials in the treatment of cutaneous wounds.
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Polycationic nanoparticles show biocompatible, broad-spectrum bactericidal properties in vitro and in vivo when incorporated in denture lining material post-maxillectomy in head and neck cancer patients. In the present study, the synthesized Crosslinked quaternary ammonium polyethylenimine nanoparticles were found to have a strong bactericidal activity against a wide variety of microorganisms rapidly killing bacterial cells when incorporated at small concentrations into soft lining materials without compromising mechanical and biocompatibility properties. This appears advantageous over conventional released antimicrobials with regard to in vivo efficacy and safety, and may provide a convenient platform for the development of non-released antimicrobials. This is a crucial issue when it comes to giving an answer to the serious and life-threatening problems of contaminations in immunocompromised patients such as orofacial cancer patient.
The development of an effective treatment able to reduce the healing time of chronic wounds is a major health care need. In this regard, our research group has recently demonstrated the in vivo effectiveness of the topical administration of rhEGF-loaded lipid nanoparticles in healing-impaired db/db mice. Here we report the effectiveness of rhEGF-NLC (rhEGF loaded nanostructured lipid carriers) in a more relevant preclinical model of wound healing, the porcine full-thickness excisional wound model. The rhEGF-NLC showed a particle size of around 335 nm, negative surface charge (− 27 mV) and a high encapsulation efficiency of 94%. rhEGF plasma levels were almost undetectable, suggesting that no systemic absorption occurred, which may minimise potential side effects and improve treatment safety. In vivo healing experiments carried out in large white pigs demonstrated that 20 μg of rhEGF-NLC topically administered twice a week increased the wound closure and percentage of healed wounds by day 25, compared with the same number of intralesional administrations of 75 μg free rhEGF and empty NLC. Moreover, rhEGF-NLC improved the wound healing quality expressed in terms of number of arranged microvasculature, fibroblast migration and proliferation, collagen deposition and evolution of the inflammatory response. Overall, these findings demonstrated that topically administered rhEGF-NLC may generate de novo intact skin after full thickness injury in a porcine model, thereby confirming their potential clinical application for the treatment of chronic wounds.
In the present study, chitosan-fibrin nanocomposites (CFNs) were prepared using a novel method and analysed for their physico-chemical properties. TEM and SEM studies revealed their size in the range of 24–28 nm with zeta potential value of +16 mV. Anti-bacterial activity of CFN
was investigated against Escherichia coli and Staphylococcus aureus. For drug delivery applications, 71% of methotrexate (MTX) was entrapped in CFNs that displayed sustained release for up to 96 h. Anti-cancer activity of MTX-CFN was evaluated on HeLa and MCF 7 cells, which showed
dose-dependent toxicity on both the cell lines. Further, the role of CFN in wound healing was studied by creating open excision wounds on albino rats. Topical application of CFN, once in two days, for up to 10 days resulted in complete healing of wounds on day 14 whereas it took 22 days in
control. Histological and biochemical analyses proved increased synthesis of collagen with active migration of fibroblasts and epithelial cells in CFN treated wounds. From our study, it is proposed that CFN may be used as a suitable candidate for drug delivery and wound healing applications.