Biomedical Materials

Lower back pain is a considerable medical problem that will impact 80% of the U.S. population at some point in their lifetime. For the most severe cases, surgical repair is necessary and is associated with annual costs upwards of $10 billion in the United States alone. To alleviate back pain, spinal fusions are a common treatment in which two or more vertebrae are biologically fused together often facilitated by a graft material. Unfortunately, iliac crest bone autograft, the current gold standard graft material, can yield insufficient fusion and is associated with considerable donor site morbidity and pain as well as is in limited supply. Therefore, new materials need to be developed in order to better coordinate healing and new bone growth in the affected area to reduce unnecessary patient burden. To address this issue, we incorporated allograft and cellulose (i.e., 0CNCs and CNFs) into a dual-crosslinked chitosan hydrogel loaded with bioactive calcium phosphate was investigated. Hydrogels were then tested for both their material and biological properties. Specifically, hydrogel swelling ratio, mass loss, ion release profile, compressive strength, in vitro biocompatibility and osteoinduction, and in vivo biocompatibility and effectiveness in a spine fusion model were assessed. Cellulose and allograft incorporation significantly improved hydrogel compressive strength and biocompatibility and CNFs were found to be a significantly more biocompatible form of cellulose than 0CNCs. Additionally, through the controlled delivery of osteoinductive simple signaling molecules (i.e., calcium and phosphate ions), dibasic calcium phosphate (DCF)-loaded CNF/chitosan hydrogels were able to induce osteoblast-like activity in murine mesenchymal stem cells. When evaluated in vivo, these hydrogels were found to be non-toxic through the subacute phase (i.e., up to 14 days). A 6-week rabbit spine fusion study found these materials excitingly achieved near complete fusion when assessed radiographically. This research provides considerable support for the utility of our novel complex biomaterial for spine fusion procedures as well as potentially for other future bone applications.

This study demonstrates the implantation of a 3D-printed small intestine construct using chitosan bioink and freeform reversible embedding of suspended hydrogels (FRESH) bioprinting technology. The research addresses the significant clinical challenges posed by inflammatory bowel disease (IBD) and short bowel syndrome (SBS), which often require surgical interventions leading to substantial loss of small intestine (SI) surface area. High costs, side effects, and donor shortages limit traditional treatments such as total parenteral nutrition and small bowel transplantation. Therefore, developing an engineered artificial intestine represents a critical need. The study employed a natural biopolymer, i.e., chitosan, known for its biocompatibility and blood compatibility, as the primary material for the bioink. The 3D-bioprinted constructs were evaluated through mechanical characterization, blood biocompatibility tests, and antibacterial assays. The mechanical properties indicated the constructs' ability to withstand significant deformation, while the blood compatibility tests showed minimal hemolysis, supporting the material's suitability for implantation. Antibacterial tests revealed that the constructs could inhibit bacterial growth, reducing the risk of implant-associated infections. Following the implantation of the prepared constructs in rats, the post-implantation analysis indicated successful integration and biocompatibility with no significant adverse reactions. The biochemical parameters, like inflammatory markers, were found to be slightly higher than the normal range. All other parameters, like bilirubin and albumins, etc, were in the normal range. This study highlights the potential of 3D-bioprinted chitosan-based constructs in organ regeneration and presents a promising solution for treating SBS and IBD. The findings support further exploration of the fabricated 3D printed biocompatible materials for medical applications in regenerative medicine and tissue engineering.

Cancer is one of the foremost reasons for global death. According to estimates, around 19.3 million instances of cancer and over 10 million fatalities were documented in the year 2020, making it one of the leading causes of death across the globe. There are still restrictions due to the absence of effective early detection and inadequate conventional therapy, which has led to poor prognosis and survival rates. This is the case despite the fact that there have been breakthroughs in diagnosis and treatment. The science of nanomedicine has achieved considerable advancements in the realm of cancer theranostics. These advancements offer a number of distinct advantages, including tumor-targeting through the increased permeability and retention effect, biocompatibility, and small size. In light of the above, the purpose of the Focus Issue on ‘Advances in Nanomedicine for Cancer Theranostics’, was introduced to highlight new research on nanomedicine-based approaches to cancer treatment. These techniques include drug and gene delivery, bioimaging, biomarker identification, diagnosis, immunotherapy, biosensors, and other precision oncology strategies. For this Focus Issue, we invited front-line researchers and authors who contributed the original research papers and topical review articles. This editorial summarizes the published articles of this collection which includes eighteen research articles and eleven review articles.

Healing bone defects remains a significant orthopedic challenge. Cell therapy and tissue engineering offer promising solutions; however, obtaining high-quality, partially or fully differentiated cells remains difficult. Therefore, developing suitable substrates to guide stem cell differentiation helps in achieving this goal. Here, an optimized polydimethylsiloxane (PDMS) substrate was created by casting the PDMS composition on isolated and fixed human osteoblasts and characterizing the biological and surface features of cell patterns. A nanolayer of hydroxyapatite (nHA) was sputtered on the cell patterns to mimic the bone extracellular matrix and enhance osteo- differentiation, providing both physical and chemical stimulations. Various physical and biological properties of patterned and non-patterned PDMS substrates with and without nHA coating were evaluated to confirm the osteo-differentiation of adipose derived mesenchymal stem cells capacity. According to the results, precise cell imprinting was successfully achieved, and nHA deposition did not adversely affect the surface topography. All substrates were biocompatible, and the combination of physical (cell imprinting)-chemical (nHA coating) stimuli significantly enhanced stem cell differentiation, as evidenced by increased alkaline phosphatase activity, upregulation of bone-specific genes, and calcium deposition. A well-designed PDMS substrate can be promising for providing osteo-differentiated stem cells in large quantities for various cell therapy and tissue engineering applications.

Polymers are large molecules composed of repeating subunits called monomers, which can be de-rived from both natural sources and synthetic processes. Due to their exceptional physicochemical properties and functional characteristics, polymers have garnered significant attention in the bio-medical field, particularly in tissue engineering. 3D printing technology, a process that manufactures three-dimensional objects by sequentially adding material based on digital models, has been widely recognized for its integration with polymers in bone tissue engineering (BTE). This review provides an overview of 3D-printed polymeric biomaterials in BTE. It begins with a discussion of the fundamental process of bone regeneration, followed by a component’s selection for polymers and 3D printing technologies. Additionally, this review comprehensively addresses the functional properties design of 3D-printed polymeric biomaterials. Finally, the current status, challenges, and future directions for the application of 3D-printed polymeric biomaterials in BTE are discussed.

There is growing evidence of myocardial hysteresis and, recently, the viscoelasticity of healthy and pulmonary hypertensive (PH) right ventricle free walls (RVFW) has been studied by stress–relaxation. However, stress–relaxation does not fully capture the in vivo deformation of the tissue, and the changes in right ventricle hysteresis behavior with PH remain unknown. Our aim was to investigate RVFW biaxial hysteresis behavior with PH. We conducted equibiaxial cyclic sinusoidal tensile testing in healthy and PH rat RVFW tissues under 20% strain, with strain rates of 0.1&1 Hz (sub-physiological), and 5&8 Hz (physiological). Elastic modulus, loop height, stored and dissipated energies, the ratio of viscosity to elasticity (V/E), and the percentage of dissipated to total energy (damping) were derived. After PH, elastic modulus was elevated in both directions, while longitudinal loop height and stored and dissipated energies were increased (p < 0.05). Despite these individual changes in viscosity and elasticity, V/E ratio and damping were maintained. We further found frequency-dependent responses of V/E ratio and damping, and these were enhanced in the diseased RVs (p < 0.05 at 5&8 Hz) than healthy RVs (p < 0.05 only at 8 Hz). Finally, we observed significant correlations between individual mechanical properties and structural changes (collagen content/myofiber width), and the correlations were stronger in the longitudinal (p ⩽ 0.006) than circumferential (p < 0.05) direction. Moreover, collagen had a much greater contribution (p ⩽ 0.002) to tissue elasticity than myofiber (p ⩽ 0.02). Multiple linear regression analyses revealed a significant role of myofibers, not collagen content, in the tissue viscosity in both directions (p < 0.05). Our results suggest the importance of incorporating tissue viscoelastic properties into pathophysiology as well as the design of cardiac biomimetic materials for advancements in cardiac health.

Curcumin is a natural polyphenolic compound derived from turmeric, which exhibits a wide range of pharmacological activities, including anti-inflammatory and promoting bone healing effects. To enhance the bioactivity of the surface of titanium implants and promote early bone integration, the pure titanium surface was modified by composite modification through electrochemical anodic oxidation and drug coating. The surface of the prepared materials was characterized by scanning electron microscopy , atomic force microscopy, X-ray photoelectron spectroscopy, and surface contact angle analyzer. The drug release performance of the modified titanium surfaces was evaluated by ultraviolet spectrophotometry. Rat bone marrow mesenchymal stem cells were extracted and identified. The effects of surface modification on cell viability were investigated through CCK-8, cell adhesion, and live/dead cell staining experiments. The effects of different surface-treated titanium sheets on osteogenic differentiation of bone marrow mesenchymal stem cells were evaluated by transwell assay, alkaline phosphatase activity assay, reverse transcription quantitative polymerase chain reaction , and mineralization nodule staining experiments. The results showed that successful loading of titanium nanotubes with curcumin was prepared, and the surface-modified titanium sheets had effective physical properties (excellent corrosion resistance, mechanical properties and hydrophilicity) and drug release capabilities. The results of in vitro cell culture experiments indicated that superior cell adhesion morphology was observed on the surface of each group of titanium sheets. TiO2 nanotubes and curcumin could significantly promote bone marrow mesenchymal stem cells proliferation and showed pleasant biocompatibility. The in vitro osteogenic induction differentiation experiments confirmed that the TiO2 nanotube structure and curcumin coating could promote osteogenic differentiation of bone marrow mesenchymal stem cells. This study provides a significant theoretical foundation and experimental support for the development of bioactive implants for dental applications.

The growing clinical need for filling defects and bone voids has led to the development of scaffolds that stimulate bone regeneration and serve as temporary models for vascularised bone growth. Additionally, these scaffolds can function as drug delivery systems to reduce inflammatory processes associated with diseases such as osteoarthritis, rheumatoid arthritis, osteoporosis, and bone cancer. Among the materials used to manufacture scaffolds, β-tricalcium phosphate (β-TCP, Ca3(PO4)2) stands out due to its excellent biocompatibility and chemical composition, closely resembling minerals from bone tissue. When combined with curcumin, calcium phosphate scaffolds offer a promising platform for drug delivery, as their tailored porous structure can provide controlled release. Curcumin enhances anti-inflammatory and antioxidant properties, thereby promoting tissue regeneration. In this study, β-TCP powders loaded with 5 and 10 mg ml⁻¹ of curcumin (designated as β-TCP/Curc 5 and β-TCP/Curc 10) were successfully obtained via freeze-drying and characterised using x-ray diffraction and Fourier-transform infrared spectroscopy to assess their crystallinity and chemical composition. The β-TCP/Curc powders were evaluated for their ability to load and release curcumin. Subsequently, β-TCP and β-TCP/Curc 5 scaffolds were prepared using 3D printing. The β-TCP/Curc 5 scaffolds were assessed for curcumin release, cytotoxicity profile, and antimicrobial activity. The β-TCP/Curc 5 powders exhibited significantly higher curcumin adsorption and good release capacity, whereas the β-TCP/Curc 10 powders displayed reduced curcumin loading and limited release efficiency. The combination of β-TCP/Curc 5 with sodium alginate produced a suitable paste for 3D printing scaffold fabrication, and the β-TCP/Curc 5 scaffolds demonstrated high similarity to the computational model. Importantly, the β-TCP scaffolds did not exhibit cytotoxicity in the MC3T3-E1 cell line, and after curcumin loading, there was no increase in cellular cytotoxicity observed. In fact, an increase in cell viability was noted compared to the control after three days of indirect assays, suggesting that this combination may be beneficial for promoting cell growth. However, the scaffolds did not show any antibacterial effects against S. aureus and E. coli under the tested conditions. This study demonstrates that adequate curcumin loading in 3D-printed β-TCP scaffolds can facilitate curcumin release at the bone healing site, potentially influencing the cellular processes involved in bone regeneration and remodelling.

Textile technologies are significantly advancing the field of tissue engineering (TE) by providing innovative scaffolds that closely mimic the extracellular matrix and address crucial challenges in tissue regeneration. Techniques such as weaving, knitting, and braiding allow for creating structures with customizable porosity, mechanical properties, and fiber alignment, which are essential for supporting cellular behaviors such as adhesion, proliferation, and differentiation. Recent developments have incorporated bioactive materials—like growth factors, peptides, and nanoparticles—into these textile-based scaffolds, greatly enhancing their functionality for applications in wound healing, skin regeneration, and organ engineering. The emergence of smart textiles, which utilize responsive polymers and nanotechnology, facilitates the on-demand delivery of therapeutic agents and provides electrical stimulation to repair neural and muscular tissues. Additionally, combining 3D bioprinting with textile principles enables the fabrication of anatomically precise, multi-layered scaffolds, expediting advancements in complex tissue reconstruction, including vascular grafts and bone scaffolds. Utilization of materials such as polycaprolactone, collagen, and silk fibroin—often in hybrid forms—ensures that these scaffolds maintain biocompatibility, mechanical integrity, and biodegradability. As functionalized textiles are explored for applications in cardiovascular, skin, and organ engineering, leveraging techniques like electro-spun nanofibers and braided vascular grafts, a transformative approach to regenerative medicine emerges. Despite ongoing challenges with vascularization and scaling, textile-engineered scaffolds promise to enable personalized, durable, and multifunctional solutions, positioning the convergence of textile science and TE to redefine future biomedical applications.

Magnetic hyperthermia has emerged as a promising approach in the pursuit of effective cancer therapies; however, its success relies heavily on the development of advanced magnetic nanomaterials. This study introduces a groundbreaking approach of intracellular magnetic hyperthermia using superparamagnetic iron nanoparticles (SPINs) specifically within breast and prostate tumors, laying a crucial foundation for the development of hyperthermia cancer therapy. In contrast to traditional anticancer treatments, our approach leverages the superior tumor retention capabilities of nanoparticles due to their intracellular cell uptake allowing efficient induced localized heating power. We developed a highly controllable synthesis method for iron nanoparticles in carbon matrix, which exhibit efficient localized heat generation by SPINs under applied magnetic field within the clinical limit, with magnetic saturation exceeding 150 emu g⁻¹, highlighting their potential for hyperthermia therapy. Characterization through scanning electron microscopy, x-ray diffraction, and vibrating sample magnetometry confirms the spherical-like shape, pure iron phase and high magnetization of the formed nanoparticles. These dispersed nanoparticles demonstrate feasibility for hyperthermia, quantified by the specific absorption rate. In vitro intracellular uptake studies using Du145 prostate and MCF7 breast cancer cell lines indicate efficient nanoparticle tumor cell-uptake. Pre- and post-hyperthermia cell viability assessments show substantial tumor cell death, with nearly 50% reduction post-magnetic field application. These findings highlight the promising potential of these advanced nanoparticles for intracellular targeted cancer therapy, particularly in solid tumors, and suggest significant avenues for further medical research and application.

Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, are leading causes of blindness globally, characterized by progressive degeneration of retinal pigment epithelium (RPE) and photoreceptor (PR) cells. Despite advancements, current therapies have not substantially arrested disease progression. Cell replacement therapy using healthy RPE and PR cells holds promise but faces obstacles such as poor cell survival, inadequate integration, and transplantation difficulties. To address these issues, tissue engineering combined with 3D printing has become a focal point. This study investigates the use of four hydrogels—GelMA, HAMA, AlgMA, and PEGDA—and their various crosslinked combinations for creating hydrogel thin-layer matrices conducive to RPE cell growth. PEGDA/GelMA hydrogel demonstrated optimal support for cell spreading and proliferation, which is not achievable with hydrogels matrices of other formulations. The relationship between the mechanical properties of PEGDA/GelMA hydrogels and cell growth was further refined. PEGDA600-20 hydrogel with a compressive modulus of 1245.07 ± 20.79 kPa was selected based on time-course viability assays, leading to the development of the optimized Fib@PEGDA/GelMA hydrogel exhibited exceptional biocompatibility. Compared to PEGDA/GelMA, CCK-8 assays demonstrated significantly improved relative cell viability at 24 h, 48 h, and 72 h, with increases of 17.73 ± 1.22%, 14.54 ± 3.63%, and 19.04 ± 2.31%, respectively on Fib@PEGDA/GelMA matrix. qRT-PCR results indicated a mitigation of epithelial-mesenchymal transition (EMT), as evidenced by downregulation of EMT markers (CDH2, COL1A1, and FN1), accompanied by reduced IL-6 levels. Fib@PEGDA/GelMA hydrogel enhanced phagocytic activity in ARPE-19 cells and promoted functional expression in hiPSC-RPEs. Additionally, the hydrogel showed favorable in vivo biocompatibility following subcutaneous implantation of RCS rats at 1, 2, and 4 weeks post-implantation evidenced by HE and Masson’s staining. This system offers a promising bioink for 3D-printed retinal cell scaffolds and paves the way for future advancements in cell replacement therapies for retinal degenerative diseases.

Herpes simplex virus type 2 (HSV-2) remains a significant public health concern due to its high rates of mortality and morbidity. While various chemotherapeutic options exist for treating HSV-2, they are often inadequate as none provide a definitive cure, and there is a growing issue of drug-resistant strains. The introduction of nanomedicine for antiviral drug delivery offers a promising avenue to enhance the effectiveness of these treatments. This study explored an innovative approach to treating HSV-2 by encapsulating valacyclovir in biodegradable polycaprolactone (PCL) using a double emulsion technique. The formulated valacyclovir-loaded polymeric nanoparticles were characterized, revealing monodispersed particles with an average hydrodynamic size ranging from 154.9 ± 2.1 to 232.8 ± 6.2 nm, along with an encapsulation efficiency of 50%–66% and a drug loading capacity of 11.6%–13.9%. Additionally, there is no significant cytotoxicity of the test compounds to Vero cells at 0.3 mg ml⁻¹ concentration with a cell viability within the range of 85 ± 13.6%−100 ± 4.8%. The antiviral activity of both the free drug (valacyclovir) and the valacyclovir-loaded polymeric nanoparticles was assessed in HSV-2 infected Vero cells. The results demonstrated that the valacyclovir-loaded nanoparticles exhibited a 1.2–1.3fold (p < 0.005) increase in antiviral efficacy compared to the free drug. This study thus presents a novel nanotechnology-based treatment approach for HSV-2, offering enhanced antiviral effectiveness over traditional treatments.

Natural substances with anti-inflammatory activity have always been the priority for human injuries. This study aims to investigate the beneficial effects and mechanism of sea cucumber protein (SCP) on wound healing, through a BALB/c mouse model and lipopolysaccharides-induced RAW 264.7 cells. We identified the mice’s serum cytokines and tissue section to find out how SCP paste works. The alteration of the nuclear factor-κB (NF-κB) pathway during the anti-inflammatory effect of SCP was also explored. The results showed that the wound healing rate in the SCP(H) group exceeded 90%, whereas it was 72.91% and 64.10% in the Control and negative control groups on day 14. New blood vessels and fibroblasts were generated in the wounds. Collagen expression increased by 13.89% and 15.12% respectively in the SCP(L) and SCP(H) groups compared with the Control group on day 14. Furthermore, SCP decreased the levels of pro-inflammatory factors (tumor necrosis factor-α, interleukin (IL)-1β, IL-6) in mice’s serum while up-regulating the level of anti-inflammatory factor (IL-10) during the healing process. Furthermore, SCP suppressed the NF-κB pathway by decreasing protein levels of phosphorylated p65 and IKKα, and increasing protein levels of IκBα.

Eggshells are regular domestic, agricultural waste, and the primary composition of eggshells is majorly of calcium, as well as trace amounts of magnesium and phosphorous. These two elements (calcium and magnesium) are also present in living organisms and play an important role in many biological processes (cell growth, muscle contraction, glycolysis, angiogenesis, and vasculogenesis). Considering their role in different biological processes, especially in angiogenesis (formation of new blood vessels from pre-existing vasculature), we hypothesized the involvement of calcium and magnesium (present in eggshells) in the nanoform may induce angiogenesis. To this context, the present manuscript attempts to design calcium-rich nanoparticles derived from both unfertilized and fertilized eggshells (U-ES and F-ES), and investigate their pro-angiogenic properties. Both U-ES nanoparticles (U-ES-NP) and F-ES nanoparticles (F-ES-NP) were developed by the calcination of raw eggshells. These nanoparticles (U-ES-NP and F-ES-NP) are characterized using various analytical techniques. These nanoparticles exhibit pro-angiogenic properties, as validated by in vitro assays (cell proliferation assay, tube formation assay, etc), ex vivo (chick aorta assay) and in vivo (chick choriallantoic membrane assay) experiments. The hemolysis experiment (ex vivo) was performed by incubating mouse RBCs with nanoparticles, which further validates the biocompatibility of these nanomaterials. Taking these results altogether, the current study demonstrates pro-angiogenic properties of biocompatible ES-NP, that could be further utilized for the treatment of several diseases and other biomedical applications after proper biosafety evaluation.

This review highlights recent advancements in hydrogel-based delivery systems incorporating natural active compounds, particularly those derived from traditional Chinese medicine (TCM), for the repair of endometrial injuries. The endometrium, known for its exceptional regenerative capacity, often requires targeted therapeutic interventions when damaged. Conventional treatment approaches frequently exhibit limited efficacy, prompting growing interest in TCM-based strategies due to their favourable safety profiles and multifaceted therapeutic potential. However, clinical translation of TCM compounds remains challenging due to issues such as poor solubility and bioavailability. Recent innovations in biodegradable polymeric hydrogels offer a promising solution, enabling controlled release of bioactive compounds and enhancing therapeutic efficacy through mechanisms such as inflammation modulation, promotion of angiogenesis, and facilitation of epithelial regeneration. This review delves into the design principles, fabrication techniques, and current applications of natural and synthetic hydrogels in endometrial repair. While preclinical findings are encouraging, significant challenges persist, including biocompatibility optimization, standardization of TCM formulations, and precise control of hydrogel degradation. Future research should focus on developing innovative materials, integrating smart responsive systems, advancing personalized treatment modalities, and conducting large-scale clinical trials. Progress in this field will depend on interdisciplinary collaboration across biomaterials science, pharmacy, TCM, and clinical medicine, paving the way for clinical adoption of these advanced therapeutic strategies.

Cartilage tissue engineering offers a promising solution for addressing severe cartilage damage. To replicate native cartilage properties, scaffolds must exhibit both load-bearing capacity and the ability to regain their original shape. Balancing elasticity and hardness remains a challenge for biomaterials currently used in cartilage tissue engineering. Polyurethane, a Food and Drug Administration-approved elastomeric biomaterial, shows promise in meeting these requirements but shows limited support for cartilage-specific extracellular matrix (ECM) accumulation by chondrocytes. In this study, we employed 3D printing to fabricate multi-layered scaffolds using two modified polyurethane formulations: one combining aromatic polyurethane with cyclic trimethylolpropane formal acrylate to enhance mechanical strength and elasticity, and another incorporating hydroxyethyl methacrylate to improve biocompatibility. These scaffolds supported chondrocyte adhesion and redifferentiation, promoting significant cartilage ECM deposition and the formation of cartilage-like sheets, which not only exhibited cartilage ECM, but also had good elasticity and compressive resistance. These findings highlight the potential of these modified polyurethanes for cartilage tissue engineering and introduce a platform for scaffold-free implantation of engineered cartilage, which could accelerate future clinical applications.

The testicular spermatogenic epithelium, the fundamental functional unit of spermatogenesis, comprises Sertoli cells and a sequence of spermatogenic cells, with the Leydig cells (LCs) playing a pivotal supporting role in sperm development. In this study, we developed a microfluidic testicular organ-on-a-chip (OoC) composed of spermatogonial stem cells, Sertoli cells, and LCs. After 28 d of culture, the testicular OoC demonstrated the formation of a spermatogenic epithelial structure, with observed proliferation and differentiation of spermatogonial stem cells. Both Sertoli and LCs were noted to perform their fundamental cellular functions and engage in intercellular communication. Applying reproductive toxicity factors to testicular OoC reduced the proliferation of spermatogonia stem cell in the chip. This testicular OoC model revealed its potential for exploring physiological functions of the testicular spermatogenic epithelium and serving as a platform for pharmacological and toxicological screening.

Uncontrolled bleeding is a critical concern in both wartime and civilian trauma emergencies. Current mechanical hemostatic patches do not always suffice to control bleeding while also not addressing rebleeding, which is often observed during patient transportation. The unmet clinical need has led to exploration of drug-loaded hemostat dressings, providing mechanical hemostasis as well as drug delivery at the bleeding site to stabilize the clots. In the present study, hemostatic nanofiber patches of poly(vinyl alcohol)/chitosan/tranexamic acid-ethamsylate (PVA/CS/TXA-E) were prepared by taking a combination of chitosan, PVA, with two different hemostatic drugs, namely TXA, and ethamsylate to exert a synergistic pharmacological augmentation of hemostat performance of the nanofibers. The PVA/CS/TXA-E nanofiber patches comprised fiber strands with a 400 nm average diameter and showed a swelling ratio of 459%. The nanofiber possessed intermittent hydrophilicity (water contact angle 32). Drug release through the nanofiber followed a non-Fickian diffusion model. Dual-drug loaded nanofibers showed a decrease in the clotting time by 24%, while activated partial thromboplastin time, prothrombin time, and platelet recalcination time decreased by 6%, 20% & 15% over the single-drug loaded nanofibers. Cytocompatibility (80% and above) and hemocompatibility (less than 8%) of the patches were established. The hemorrhage control capacity was studied in vitro and ex vivo on rabbit skin. In vivo results corroborated the hemostat performance and evidence of the presence of granularity indicative of wound healing progression. Our results suggest PVA/CS/TXA-E potential as an effective hemostatic nanofiber with biocompatibility for managing hemorrhage and facilitating wound healing post-surgery.

The middle ear, which lies between the external auditory canal and the inner ear (cochlea), comprises the tympanic membrane, the ossicular chain (i.e. malleus, incus, and stapes), as well as the associated muscles, ligaments, and the middle ear cavity. Its primary function is to transmit vibratory energy (sound pressure) from the air to the cochlear fluids via the ossicular chain. This part of the ear can be damaged by cholesteatoma, which can affect all three ossicles, necessitating ossiculoplasty to restore sound transmission. Ossiculoplasty is the preferred intervention for restoring the mechanism of sound transmission in patients with ossicular deformities. However, the complexity and extended duration of the surgery can significantly impact the patient’s quality of life. To address these challenges, our work employs 3D printing technology for the reconstruction of the patient’s ear ossicles. This involves detailed 3D modeling and reconstruction of the ear ossicles to obtain precise measurements and visualize the unique anatomical structure of each patient. The model presented in this study is a prototype designed to validate the form and dimensions of a total ossicular replacement prosthesis. Our radiologists and traumatologists reviewed both the form and dimensions and deemed them realistic, ensuring they aligned with clinical requirements. It is important that medical devices, especially those designed for long-term implantation, must undergo strict regulatory testing, which can take several years. Standards such as International Organization for Standardization 13485, 14971, and 5832 require thorough validation to ensure safety, effectiveness, and quality. While this prototype represents an important step, further testing, and regulatory approval will be necessary before it can be used in clinical settings. By leveraging advanced materials and precise 3D printing techniques, these custom-made prostheses simplify the surgical procedure and enhance patient outcomes by providing tailored solutions that meet specific anatomical and functional needs. This innovative approach represents a significant advancement in treating ossicular deformities, ensuring both efficacy and improved patient satisfaction.

Overcoming the limitations of conventional antioxidants in treating oxidative stress-related neurodegenerative diseases (NDs) remains a critical challenge, thus more effective antioxidant strategies need to be studied urgently. To address this, we developed a novel pH-responsive drug-delivery hydrogel, PCA-g-CMCS/OXG, by grafting protocatechuic acid (PCA) onto carboxymethyl chitosan (CMCS) via amide bonds and blending it with oxidized xanthan gum (OXG) to form dynamic imine bonds. The conjugate PCA-g-CMCS achieved an unprecedented grafting efficiency of 785.3 mg g⁻¹ through optimized reactant ratios, pH, and reaction time. And the multifunctional hydrogel PCA-g-CMCS/OXG offers three key advantages: (1) rapid tunable gelation time (10–110 s) and robust mechanical/rheological properties enabling injectable and sprayable applications; (2) self-healing capability and sustained pH-responsive PCA release over 15 d, ensuring long-term therapeutic efficacy; and (3) superior cytoprotection, as the hydrogel exhibited excellent biocompatibility with SH-SY5Y neuronal cells and significantly increased cell viability to 76.60% from H2O2-induced oxidative damage (vs. 48.61% for control, p < 0.01). Therefore, the smart Schiff’s base hydrogel is a drug loaded material with great clinical application prospect for the treatment of NDs.

Ovarian cancer is the most prevalent fatal, gynecological malignancy in women, resulting in poor survival rate (fifth in cancer deaths) due to its asymptomatic nature. Unmet medical challenges for ovarian cancer are associated with several constraints such as poor bioavailability, nonspecificity, and toxicity-related issues. Targeted drug delivery systems may overcome the existing limitations. Utilizing the concept of overexpression of folate receptors (FRs) in ovarian carcinoma, we have designed FRs-targeted drug delivery systems (AgNNPs-FA) by combining silver nitroprusside nanoparticles (AgNNPs) because of their inherent anticancer properties, as established by our group, and folic acid (FA) as targeting agent that attack FRs in this study. Initially, both AgNNPs and AgNNPs–FA were designed and later characterized using several analytical tools such as dynamic light scattering, x-ray diffraction, scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, high-performance liquid chromatography, and Fourier transform–infrared spectroscopy, etc. The in vitro cell viability assay in a Chinese hamster ovary cell line suggests the biocompatible nature of AgNNPs–FA. The targeted anticancer activity of the AgNNPs–FA is established in human ovarian adenocarcinoma (SK-OV-3) via several in vitro assays and compared with AgNNPs. All in vitro assays (cell viability assay, thymidine incorporation assay, scratch assay, cell cycle, apoptosis assay, and tunnel assay) in SK-OV-3 and in vivo experiments (chorioallantoic membrane assay) in fertilized eggs with AgNNPs–FA exhibit more anticancer activity in a targeted fashion than AgNNPs. The plausible mechanisms behind the anticancer activity of the nanoparticles were demonstrated using the ROS assay (DCFDA and DHE staining), JC-1 staining, immunocytochemistry staining (Ki-67), and Western blot analysis. The results altogether support the idea that this targeted drug delivery system could be used as an alternative treatment strategy for ovarian cancer and other cancers with the overexpression of FRs.

Reconstruction using cartilage tissue is necessary to address deformities of the nose, ears, and maxillofacial region in several cases. However, autologous cartilage tissue transplantation is limited in the amount that can be harvested owing to invasiveness to the human body. Moreover, artificial materials such as implants cannot be used in many situations, given their potential to induce reactions to foreign bodies. Therefore, there is a growing demand for biomaterials that are less likely to cause foreign body reactions. Given that a tissue with a functionally superior three-dimensional (3D) structure can replace autologous tissue and artificial materials, we have developed a 3D cultured cartilage tissue without scaffolding material and are working toward its practical application. To achieve an off-the-shelf product that allows prolonged storage, the tissue was fixed with glutaraldehyde to maintain high strength for subsequent processing and management. Although tissue fixation with glutaraldehyde may cause calcification due to the deposition of calcium phosphate, calcification can be prevented by washing with high-concentration ethanol. We generated 3D cultured cartilage tissues using induced pluripotent stem cell-derived limb bud mesenchymal cells and an original cell self-culture aggregation method. The generated tissues were subjected to an anti-calcification treatment with glutaraldehyde and 80% ethanol. The treated tissue had improved stability and strength with minimal calcification. The tissue retained its physical properties that were effectively processable and could be processed into an ear-like shape.

Implant–associated infections and aseptic loosening of prosthesis due to insufficient secondary stability continue to present a challenging issue in arthroplasty. Potential solutions include bioactive coatings to promote osseointegration. With this in mind, this study aims to investigate and compare thin bioactive and bioresorbable β-tricalcium phosphate (β-TCP) and calcium alka-li orthophosphate (GB14) coatings, both produced via high velocity suspension flame spraying. To achieve an additional antibacterial effect and to prevent infections through aerosolized contamination, Cu-doped β-TCP supraparticles (SP) are incorporated into the coatings. β-TCP and GB14 coatings with 0.5 wt.% Cu-doped β-TCP SP each were investigated. According to ISO EN 10993–14, a degradation test was performed in TRIS-buffer at pH 7.4 over 120 h. Biocompatibility testing was performed on human osteoblasts using live/dead staining on days 1, 3 and 7 to simultaneously visualize viable and non-viable cells, while cytotoxicity was assessed over a 3 d period with the cytotoxicity assay. To evaluate the antibacterial efficacy, safe airborne antibacterial assays using S. aureus and E. coli were performed. Our investigations demonstrate that Cu is released from the coatings over a period of 120 h. The released Cu-amount results in a significant reduction in colony forming units across all coatings, while only negligibly imparing the behavior of the human osteoblasts. Both coatings exhibit high biocompatibility, with cell counts varying depending on the amount of Cu released. Cytotoxicity testing showed no cytotoxic effects for the samples examined.

Obesity is a prevalent and potentially fatal disorder in industrialized nations, often due to an imbalance between calorie intake and energy expenditure. The study investigates the effects of Ankaferd Blood Stopper (ABS), platelet-rich plasma (PRP), and Momordica charantia (MC) on obese rats with sciatic nerve injuries using stereological and electron microscopic techniques. Twenty-four female Sprague Dawley rats, aged 8–10 weeks, were divided into three groups: the obese gap ABS group (OGABS), the obese gap PRP group (OGPRP), and the obese gap MC group (OGMC). A five-mm nerve block was resected approximately 10 mm above the nerve branch. The gap region was then surrounded and closed by a collagen membrane in tube form. Materials such as ABS, PRP, and MC were injected into the tubes of each group. Electromyography and histological procedures were performed after 12 weeks of surgery to investigate their structural repair and functional promotion of nerve regeneration. A significant increase in the number of myelinated axons in OGMC was found. In addition, the latency values in OGMC were more critical than in the OGABS and OGPRP groups, indicating better myelination. PRP and ABS positively affected nerve gap repair, favoring regenerating unmyelinated axons. Due to increased amplitude values, PRP and ABS have also improved axonal area regeneration. Collagen tubes containing ABS, PRP, and MC may help repair and close peripheral nerve gaps in obese rats, which could be beneficial in closing peripheral nerve resection and demyelination. The study’s findings indicate that these collagen tubes can have a therapeutic effect on peripheral nerve regeneration in obese models.

In today’s emergency medical field, rapid hemostasis and wound healing technologies are of paramount importance. However, traditional methods, although effective, have limitations such as slow hemostasis, susceptibility to infection, and unsuitability for irregular wounds. To address these issues, this study combined methacrylated hyaluronic acid (HAMA) with zinc chondroitin sulfate (CSZn) to successfully develop a novel sprayable photocurable hydrogel, CSZn@HAMA. Material characterization confirmed that CSZn was effectively loaded into HAMA, while retaining HAMA’s photocurable and sprayable properties. This allows the CSZn@HAMA hydrogel to rapidly solidify and form a tight protective film over the wound after spraying. Further cell experiments demonstrated that this hydrogel has significant anti-inflammatory effects and can effectively promote collagen production and angiogenesis. Therefore, CSZn@HAMA has emerged as a promising biomaterial for wound management in emergency medical care.