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Biomimetic porous scaffolds for bone tissue engineering
Abstract
Increased use of reconstruction procedures in orthopedics, due to trauma, tumor, deformity, degeneration and an aging population, has caused a blossom, not only in surgical advancement, but also in the development of bone implants. Traditional synthetic porous scaffolds are made of metals, polymers, ceramics or even composite biomaterials, in which the design does not consider the native structure and properties of cells and natural tissues. Thus, these synthetic scaffolds often poorly integrate with the cells and surrounding host tissue, thereby resulting in unsatisfactory surgical outcomes due to poor corrosion and wear, mechanical mismatch, unamiable surface environment, and other unfavorable properties. Musculoskeletal tissue reconstruction is the ultimate objective in orthopedic surgery. This objective can be achieved by (i) prosthesis or fixation device implantation, and (ii) tissue engineered bone scaffolds. These devices focus on the design of implants, regardless of the choice of new biomaterials. Indeed, metallic materials, e.g. 316L stainless steel, titanium alloys and cobalt chromium alloys, are predominantly used in bone surgeries, especially in the load-bearing zone of prostheses. The engineered scaffolds take biodegradability, cell biology, biomolecules and material mechanical properties into account, in which these features are ideally suited for bone tissue repair and regeneration. Therefore, the design of the scaffold is extremely important to the success of clinical outcomes in musculoskeletal surgeries.
... . Schematic presentation of crosslinking of polyguloronate sequences of the alginate (A chain by a dimerization mechanism with Ca 2+ ions via formation of the "egg-box" structure. Form porous scaffolds made of crosslinked hydrogels enable bodily fluids transport through their ma and can be used for tissue engineering and bone regeneration [5,14]. ...
... One of the methods to produce macroporous composite scaffolds based on AL a mineral particles comprises mixing of an alginate with particle dispersion in a CaCl2 lution followed by controlled slow gelation and subsequent freeze-drying [14,20]. Und standing the evolution and kinetics of crosslinking, directly impacting the mechani properties and porosity, is critical for the fabrication of composite AL structures Porosity control is important, because fluid flow through scaffolds is important for s cessful fulfilment of complex parameters such as nutrient passage, cell growth, metabo product removal and tissue regeneration [24]. ...
... chain by a dimerization mechanism with Ca 2+ ions via formation of the "egg-box" structure. Formed porous scaffolds made of crosslinked hydrogels enable bodily fluids transport through their matrix and can be used for tissue engineering and bone regeneration [5,14]. ...
Alginate hydrogels have gathered significant attention in biomedical engineering due to their remarkable biocompatibility, biodegradability, and ability to encapsulate cells and bioactive molecules, but much less has been reported on the kinetics of gelation. Scarce experimental data are available on cross-linked alginates (AL) with bioactive components. The present study addressed a novel method for defining the crosslinking mechanism using rheological measurements for aqueous mixtures of AL and calcium chloride (CaCl2) with the presence of hydroxyapatite (HAp) as filler particles. The time-dependent crosslinking behaviour of these mixtures was exploited using a plate–plate rheometer, when crosslinking occurs due to calcium ions (Ca²⁺) binding to the guluronic acid blocks within the AL polymer, forming a stable “egg-box” structure. To reveal the influence of HAp particles as filler on crosslinked sample morphology, after rheological measurement and crosslinking, crosslinked samples were freeze-dried and their morphology was assessed using an optical microscope and SEM. It was found that the addition of HAp particles, which are known to enhance the mechanical properties and biocompatibility of crosslinked AL gels, significantly decreased (usually rapidly) the interaction between the Ca²⁺ and AL chains. In this research, the physical “shielding” effect of HAp particles on the crosslinking of AL with Ca²⁺ ions has been observed for the first time, and its crosslinking behaviour was defined using rheological methods. After crosslinking and rheometer measurements, the samples were further evaluated for morphological properties and the observations were correlated with their dewatering properties. While the presence of HAp particles led to a slower crosslinking process and a more uniform development of the rheological parameters, it also led to a more uniform porosity and improved dewatering properties. The observed effects allow for a better understanding of the crosslinking process kinetics, which directly affects the physical and chemical properties of the AL gels. The shielding behaviour (retardation) of filler particles occurs when they physically or chemically block certain components in a mixture, delaying their interaction with other reactants. In hydrogel formulations, filler particles like hydroxyapatite (HAp) can act as barriers, adsorbing onto reactive components or creating physical separation, which slows the reaction rate and allows for controlled gelation or delayed crosslinking. This delayed reactivity is beneficial for precise control over the reaction timing, enabling the better manipulation of material properties such as crosslinking distribution, pore structure, and mechanical stability. In this research, the physical shielding effect of HAp particles was observed through changes in rheological properties during crosslinking and was dependent on the HAp concentration. The addition of HAp also enabled more uniform porosity and improved dewatering properties. The observed effects allow for a better understanding of the crosslinking process kinetics, which directly affects the physical and chemical properties of the AL gels.
... Scaffolds for bone engineering must possess mechanical properties that align with the tissues at the implantation site to offer sufficient mechanical support and prevent excessive deformation [79,80]. Maxillofacial bone exhibits a higher remodeling rate and lower mineralization and mass density than the femur, primarily due to larger osteocyte lacunae [25,81]. ...
... In addition to direct activation of intracellular signaling in bone repair mechanisms, bioactive ions in bone regeneration are also applied to activate the bone regeneration process; 70% of the mass of bone is made up of minerals, 20% of collagen, and the remaining 10% is made up of various proteins, polysaccharides, and lipids [80]. The main minerals found in bones include magnesium, zinc, calcium, and strontium. ...
Maxillofacial bone defects can have a profound impact on both facial function and aesthetics. While various biomaterial scaffolds have shown promise in addressing these challenges, regenerating bone in this region remains complex due to its irregular shape, intricate structure, and differing cellular origins compared to other bones in the human body. Moreover, the significant and variable mechanical loads placed on the maxillofacial bones add further complexity, especially in cases of difficult-to-treat medical conditions. This review provides a brief overview of medication-related osteonecrosis of the jaw (MRONJ), highlighting the medication-induced adverse reactions and the associated clinical challenges in treating this condition. The purpose of this manuscript is to emphasize the role of biotechnology and tissue engineering technologies in therapy. By using scaffold materials and biofactors in combination with autologous cells, innovative solutions are explored for the repair of damaged facial bones. The ongoing search for effective scaffolds that can address these challenges and improve in vitro bone preparation for subsequent regeneration in the maxillofacial region remains critical. The primary purpose of this review is to spotlight current research trends and novel approaches in this area.
... [4,5] The initial biomaterials were designed as temporary biological scaffolds to fill in tissue defects to maintain the structural integrity of the damaged site, provide physical structural support, and promote cell adhesion and growth. [6,7] Along with the rapid progress in cytology, molecular biology, etc., and intensive study of the interaction between cells and biological materials, researchers pay more attention to the function of biomaterials. [8][9][10] Biomaterials loaded with stem cells, [11] drugs, [12] growth factors, [13] exosomes, [14] small molecule ribonucleic acid and other bioactive Qianfen Qi is a graduate student at the School of Pharmacy, at Yantai University. ...
Tissue engineering aiming to develop and manufacture bioactive tissue or organ substitutes has been extensively studied. As an ideal scaffold material, the microsphere‐hydrogel combination system (MHCS), which combines the excellent functionalities of hydrogels and the unique structural advantages of microspheres, has been widely used in the development of biological substitutes for tissue engineering. With adjustable mechanical properties, the MHCS can simulate extracellular matrix‐like microstructure and microenvironment conducive to cell growth. These properties endow the MHCS with unique advantages in tissue repair, leading to significant progress in the regeneration of bone, skin, blood vessels, nerves, and other tissues. In this paper, we reviewed the latest progress in MHCS construction based on natural polymers, synthetic polymers, inorganic materials, and their composites. We also classified the raw materials that were utilized for the construction of microspheres and hydrogels and discussed the properties and applications of MHCS. Finally, the challenges and perspectives of MHCS were emphasized and pointed out the direction of future development, such as conducted advanced processing technologies and multidisciplinary cooperation to solve the limitations of uneven microsphere distribution and mismatched degradation rates, thus providing a reference for the design and fabrication of MHCS in the field of tissue engineering.
... The tumor prosthesis is currently considered a better medical technique for the limb reconstruction because of the key features of rapid surgical procedure and immediate postoperative weight bearing in comparison with the biological reconstruction. Titanium (Ti) based alloys with desirable mechanical strength, high corrosion resistance and better biocompatibility are qualified for being an implant material [1,2]. Unfortunately, the utilization of such materials as a tumor prosthesis remains challenging because of the potential infection and local recurrence in limb sparing surgery. ...
The success of tumor prosthesis relies on the preclusion of deep infection and local recurrence in limb sparing surgery. The orthopedic implants enabling to simultaneously possess the antibacterial function and anticancer ability have become a desirable local therapy in the treatment of bone cancer. In this regard, we proposed a promising concept of the sequential release in a dual-drug system by combing titania nanotubes and chitosan as drug nanoreservoirs and sustained release films, respectively. An electrochemical anodization technique, controlled by anodization voltage, electrolyte composition, and processing time, was used to fabricate self-ordered titania nanotubes on the titanium surface, with their lengths simply tuned by the processing time, for drug loading. Two drugs of cisplatin and vancomycin as model anticancer and antibiotic, respectively, were sequentially loaded in nanotubes to investigate the release kinetics. The release profiles of cisplatin and vancomycin were found to be related to the spatial positioning of each drug on the nanotubes. Such a release sequence can be attributed to the anisotropic diffusion of drugs from the nanotubes, which can be further sustained for over four weeks through chitosan coverage. The drug release behavior was first evaluated in water using ultraviolet-visible spectroscopy for the quantitative analysis of release kinetics over time. The influence of dual-drug-loaded nanotubes on the growth of staphylococcus aureus and osteogenic sarcoma in vitro was systematically evaluated for the therapeutic efficacy of bone cancer treatment. A high correlation between the viabilities of bacteria and cells and dual-drug release profiles was observed, indicating the feasibility of our nanotube-based concept utilizing a sequential release pattern to combat initial bacterial infection and prevent local recurrence.
... Naturally, a native bone has ions in its composition such as Mg 2+ , Sr 2+ , Zn 2+ , F − , Cl − , CO 3 2− , and others. 25,26 Moreover, added metal ions were shown useful to improve the biocompatible behavior and the mechanical properties of TCP. [27][28][29] TCP (CAS number: 7758-87-4) and "TCP7" doped with 10 mol% Mg 2+ , 1.67 mol% Mn 2+ , 1.67 mol% Zn 2+ , and 1.67 mol% Fe 3+ were prepared following the protocol reported in refs. ...
The design of biomaterials highly biomimetic of bone has been associated with chemical compositions rich in metal ions, as well as with the replication of different levels of physiological porosity, fundamental for the interconnectivity, and consequent vascularization of the tissue. The usual numerical models that replicate the microstructure of bioceramics are mainly based on a highly complex molecular scale. In this work, easy‐to‐obtain real two‐dimensional (2D) microstructure images of bioceramics are used to obtain the digital three‐dimensional (3D) microstructure of tricalcium phosphate (TCP) doped with several metal ions and four levels of porosity. The methodology for segmenting the two‐phase microstructure (dense TCP and pores), its grain boundaries, area and grain size distribution was calculated to obtain three numerical representative volume sizes of 7, 11, and 15 µm³. Young modulus calculations showed an excellent similarity with experimental values, and much higher proximity than literature‐available analytical methods:. 9.3 GPa, 24.9 GPa, 32.5 GPa, and 40.4 GPa for 48.5%, 30.2%, 18.9%, and 10.3% of porosity, respectively, with higher accuracy correlated with the use of higher edge length values.
... AM was applied first to biodegradable pure Zn with fully densified and porous structures [8,9]. AM porous Zn showed compressive mechanical properties compatible with cancellous bone, thereby possessing the capability for bone repair [10,11]. For bone fixation, however, the tensile properties of even solid AM Zn fall short of the design requirements [12][13][14], let alone those of porous AM Zn. ...
... Moreover, the implants must possess adequate strength to withstand everyday physical stress and reduce the chances of failure due to fatigue, a factor determined by the implant's peak stress [48][49][50]53,54]. Furthermore, the implants should maintain a stiffness similar to that of the host bones, defined by the stiffness of the implant, to prevent bone degradation due to stress shielding after surgery [49,[55][56][57]. Earlier scholarly work suggested TPMS as the preferred topologies due to their uniform curvature, large specific surface area, high strength, and structural match to that of human trabecular bones [58,59]. ...
The progression of additive manufacturing has paved the way for in-depth studies of various strut-, plate-, and sheet/shell-based cellular (meta)materials. Despite their promising mechanical properties, these metamaterials are highly sensitive to manufacturing defects. This study investigates the imperfection sensitivity of stochastic and periodic triply periodic minimal surface (TPMS) cellular materials by comparing imperfect additively manufactured samples to simulated defect-free lattices. Stochastic TPMS sheet-network lattices, using Schwarz-Diamond, Schoen−IWP, and Fischer-Koch S topologies, and their periodic counterparts, are investigated across various relative densities. Samples were additively manufactured using laser powder bed fusion of titanium alloy powder to evaluate the damage-tolerance of these cellular materials. Microstructural analysis was performed using micro-CT and SEM to assess 3D printability and defect density. Stochastic TPMS cellular materials demonstrated remarkable resistance to additive manufacturing defects compared to their periodic counterparts. In the presence of defects, stochastic TPMS sheet-based cellular materials maintain their stretching-dominated deformation behavior, whereas the deformation mode of the periodic counterparts was altered to a bending-dominated deformation. The reduced defect sensitivity allows superior mechanical performance of stochastic TPMS lattices at lower relative densities, where defects are most prominent. Numerical simulations indicate that defect-free periodic TPMS lattices display superior mechanical properties to their stochastic counterparts at all relative densities and show a clear effect of parent topology. This work expands on the understanding of the mechanical behavior of stochastic TPMS cellular materials and facilitates further improvements in their damage-tolerance and potential applications in various engineering fields.
... The improved accuracy when using Butterworth filters compared to the unfiltered dataset and the differences between various Butterworth filters indicate the importance of optimizing filter parameters for these types of images. of functionalized bioactive coatings, iv) stimuli responsive hydrogels, v) advanced imaging [8]. The control of the porosity and the pore size on the nanofibers are important parameters in biomaterial-cell interaction and these can both be fabricated with high control aiming to mimic biological systems [9,10]. These three-dimensional structures can be constructed using nanofibers produced by electrospinning and the whole serves as an extracellular matrix that provides mechanical support for the biological samples that can be studied [11]. ...
Developments in the medical field have opened the opportunity to conduct analyses on a personalized patient level. One of the important analyses that can be conducted is the cellular response to engineered materials, and the most appropriate non-invasive methods are imaging. These images of the cells are unstained brightfield images, as they are acquired from multiparametric microfluidic chambers in the presence of biomaterials and fluids that can change the optical path length over time as the cells’ health state is monitored. These experimental conditions lead to an image dataset with unique illumination, texture, and noise spectrum. This study explores the optimization of supervised cell classification by combining feature extraction architectures and machine learning classifiers, with a focus on applications in biomaterial risk assessment. Brightfield microscopy images of three cell types (A549, BALB 3T3, and THP1) were analyzed to evaluate the impact of Inception V3, Squeeze Net, and VGG16 architectures paired with classifiers including KNN, Decision Tree, Random Forest, AdaBoost, Neural Networks, and Naïve Bayes. Dimensionality reduction using Information Gain was applied to improve computational efficiency and accuracy. Butterworth filters with varying parameters were used to balance the enhancement of image features and noise removal, improving classification performance in certain cases. Experimental results demonstrate that the VGG16 architecture, when paired with Neural Networks, achieves higher classification accuracy as measured by different metrics. The improved accuracy when using Butterworth filters compared to the unfiltered dataset and the differences between various Butterworth filters indicate the importance of optimizing filter parameters for these types of images.
... This property is modulated by the cell-ECM interaction. 102 At the same time, the appropriate design of a scaffold with the same mechanotransductional signals to bone is required. [103][104][105] Biodegradability plays a key role in bone engineering and its rate must be inversely proportional to the bone deposition rate to mimic natural bone physiology. ...
Bone related disorders are highly prevalent, and many of these pathologies still do not have curative and definitive treatment methods. This is due to a complex interplay of multiple factors, such as the crosstalk between different tissues and cellular components, all of which are affected by microenvironmental factors. Moreover, these bone pathologies are specific, and current treatment results vary from patient to patient owing to their intrinsic biological variability. Current approaches in drug development to deliver new drug candidates against common bone disorders, such as standard two-dimensional (2D) cell culture and animal-based studies, are now being replaced by more relevant diseases modelling, such as three-dimension (3D) cell culture and primary cells under human-focused microphysiological systems (MPS) that can resemble human physiology by mimicking 3D tissue organization and cell microenvironmental cues. In this review, various technological advancements for in vitro bone modeling are discussed, highlighting the progress in biomaterials used as extracellular matrices, stem cell biology, and primary cell culture techniques. With emphasis on examples of modeling healthy and disease-associated bone tissues, this tutorial review aims to survey current approaches of up-to-date bone-on-chips through MPS technology, with special emphasis on the scaffold and chip capabilities for mimicking the bone extracellular matrix as this is the key environment generated for cell crosstalk and interaction. The relevant bone models are studied with critical analysis of the methods employed, aiming to serve as a tool for designing new and translational approaches. Additionally, the features reported in these state-of-the-art studies will be useful for modeling bone pathophysiology, guiding future improvements in personalized bone models that can accelerate drug discovery and clinical translation.
... At present, autografts are considered as the gold standard for treating critical-sized bone defects [3]. However, the limited availability of autograft sources severely restricts their application [4], not to mention the potential for complications from additional surgeries [5]. Bone tissue engineering (BTE) is transforming the bone-grafting materials to treating bone defect and has the potential to significantly improve the quality of life for millions of individuals [6]. ...
Inspired by the initial mineralization process with bone matrix vesicles (MVs), this study innovatively developed a delivery system to mediate mineralization during bone regeneration. The system comprises nanofibrous chitosan microspheres (NCM) and poly (allylamine hydrochloride)-stabilized amorphous calcium phosphate (PAH-ACP), which is thereafter referred to as NCMP. NCM is synthesized through the thermal induction of chitosan molecular chains, serving as the carrier, while PAH-ACP functions as the mineralization precursor. Additionally, the nanofibrous network of NCMP mimics the architecture of natural extracellular matrix (ECM), creating an optimal niche for the active adhesion of stem cells to its surface, exhibiting good biocompatibility, immunoregulation, and osteogenic performance. In vivo, NCMP effectively recruits cells and mineralizes collagen, modulates cell behavior and differentiation, and promotes in situ biomineralization in rat calvarial defects. These results underscore the dual efficacy of NCMP not only as an effective delivery system for mineralization precursors but also as ECM-mimicking bio-blocks, offering a promising avenue for enhancing the repair and regeneration of bone defects.
... By employing a viable BTE strategy that integrates scaffolds, growth factors and cells, the bone tissue could be regenerated inside the body with full functions in a regulated manner [3,4]. In recent years, biomimicking scaffolds have gained much attention as it is believed that scaffolds possessing similar geometrical features to those of native bone could have better ability and efficiency for bone regeneration [5][6][7]. Natural human long bones exhibit heterogeneous structures with porosity and pore size gradients from the peripheral cortical bone to central cancellous bone [8,9]. The cortical bone is highly compact with less than 10 % porosity, ensuring sufficient mechanical properties [10]. ...
Human long bones exhibit pore size gradients with small pores in the exterior cortical bone and large pores in the interior cancellous bone. However, most current bone tissue engineering (BTE) scaffolds only have homogeneous porous structures that do not resemble the graded architectures of natural bones. Pore-size graded (PSG) scaffolds are attractive for BTE since they can provide biomimicking porous structures that may lead to enhanced bone tissue regeneration. In this study, uniform pore size scaffolds and PSG scaffolds were designed using the gyroid unit of triply periodic minimal surface (TPMS), with small pores (400 μm) in the periphery and large pores (400, 600, 800 or 1000 μm) in the center of BTE scaffolds (designated as 400-400, 400–600, 400–800, and 400–1000 scaffold, respectively). All scaffolds maintained the same porosity of 70 vol%. BTE scaffolds were subsequently fabricated through digital light processing (DLP) 3D printing with the use of biphasic calcium phosphate (BCP). The results showed that DLP 3D printing could produce PSG BCP scaffolds with high fidelity. The PSG BCP scaffolds possessed improved biocompatibility and mass transport properties as compared to uniform pore size BCP scaffolds. In particular, the 400–800 PSG scaffolds promoted osteogenesis in vitro and enhanced new bone formation and vascularization in vivo while they displayed favorable compressive properties and permeability. This study has revealed the importance of structural design and optimization of BTE scaffolds for achieving balanced mechanical, mass transport and biological performance for bone regeneration.
... For each group, 50 pores were randomly selected from random 3D images for pore size measurement, and the average pore sizes of groups H1-5 were 522.920 µm, 469.947 µm, 353.041 µm, 295.017 µm, and 204.100 µm, respectively. Pores in the range of 100-500 µm in size are usually considered suitable for bone regeneration [50,51]. Among them, scaffolds with pore sizes between 300 and 500 µm and porosities higher than 50% not only promote cell proliferation and osteogenic differentiation but also do not impair mechanical properties [52]. ...
Ultraviolet-assisted Direct Ink Writing (UV-DIW), an extrusion-based additive manufacturing technology, has emerged as a prominent 3D printing technique and is currently an important topic in bone tissue engineering research. This study focused on the printability of double-network bioink (Nano-hydroxyapatite/Polyethylene glycol diacrylate (nHA/PEGDA)). Next, we search for the optimal UV-DIW printing parameters for the scaffold formed by nHA-PEGDA. In the end, we developed a scaffold that has outstanding structural integrity and can repair bone defects. Achieving high-quality UV-DIW printing can be challenging due to a variety of factors (slurry solid content, rheology, printing conditions, etc.). At present, there are limited reports about precise parameter configurations for UV-DIW printing. We optimised the solid composition of the slurry by varying the quantities of nHA and PEGDA, establishing the maximum solid content (40 wt%) permissible for scaffold shaping. Consequently, we examined the influence of several factors (nozzle diameter, air pressure, and printing rate) on the surface morphology of the scaffolds and determined the ideal conditions to attain scaffolds with superior printing accuracy. The findings demonstrate excellent controllability, repeatability, and precision of the entire printing process. Finally, we evaluated the scaffolds that most effectively fulfilled the requirements for bone regeneration by examining their surface morphology and mechanical characteristics. The experimental findings indicate that nHA-PEGDA scaffolds fulfil the compressive strength requirements for bone tissue and possess promising applications in bone regeneration. This study demonstrates that the nHA-PEGDA bioink possesses significant potential as a scaffold material for bone tissue regeneration, exhibiting exceptional shape integrity and mechanical capabilities. The study found the optimal parameters for bio-3D printers and gave UV-DIW an exact data reference for making the nHA-PEGDA scaffold. In addition, it is a useful guide for 3D printing biomaterial scaffolds.
... The improvement of living standards and medical conditions substantially extend the life expectancy of the population, which increases the incidence rate of dental and orthopedic diseases and thus the need for load-bearing prosthetic replacement [ 1 ]. Biomaterials such as titanium and its alloys, stainless steel, Co-Cr-Mo alloys were used as orthopedic implants [ 2 ]. ...
Despite that the clinical application of titanium-based implants has achieved great success, patients’ own diseases and/or unhealthy lifestyle habits often lead to implant failure. Many studies have been carried out to modify titanium implants to promote osseointegration and implant success. Recent studies showed that exosomes, proactively secreted extracellular vesicles by mammalian cells, could selectively target and modulate the functions of recipient cells such as macrophages, nerve cells, endothelial cells, and bone marrow mesenchymal stem cells that are closely involved in implant osseointegration. Accordingly, using exosomes to functionalize titanium implants has been deemed as a novel and effective way to improve their osseointegration ability. Herein, recent advances pertaining to surface functionalization of titanium implants with exosomes are analyzed and discussed, with focus on the role of exosomes in regulating the functions of osseointegration-related cells, and their immobilization strategies as well as resultant impact on osseointegration ability.
The corrosion properties of PBAT/LDH coating on mild steel substrate was investigated. Tafel tests and electrochemical impedance spectroscopy tests (EIS) was used to analyze the corrosion resistance of the coating on the mild steel substrates. The morphological characteristics of the coatings was done using the scanning vibrating electrode technique (SVET) and environmental scanning electron microscopy (ESEM). Buffered saline solution containing NaCl-0.138 M, KCl-0.0027 M at room temperature and pH of 7.4 was used as electrolyte in the 3 corrosion tests. The tafel results showed that least corrosion current density value of 0.315 (μA/cm2) was recorded for 50 % LDH concentration in PBAT. This suggests that 50 % LDH in PBAT was about 98.5 % more corrosion efficient than 1018 bare mild steel and 0.7 % more that the 65 % concentration. The EIS results showed a similar trend. The 65 % LDH concentration showed about 25 % greater impedance to current flow over the 50 % LDH concentration in both the nyquist and bode plots. The SVET results revealed that the greatest corrosion protection of the mild steel substrates was observed with 50 % and 65 % LDH coating. This proved that an increased concentration of LDH in PBAT could potentially improve the corrosion resistance of mild steel when in service in a phosphate buffered saline environment.
Owing to their unique biological effects and physicochemical properties, nanomaterials have garnered substantial attention in the field of bone tissue engineering (BTE), targeting the repair and restoration of impaired bone tissue. In recent years, strategies for the design and optimization of nanomaterials through thiolation modification have been widely applied in BTE. This review concisely summarizes the categories of nanomaterials commonly used in BTE and focuses on various strategies for the modification of nanomaterials via thiolation. A multifaceted analysis of the mechanisms by which thiolated nanomaterials enhance nanomaterial–cell interactions, promote drug loading and release, and modulate osteogenic differentiation is presented. Furthermore, this review introduces biomedical applications of thiolated nanomaterials in BTE, including as scaffold components for bone regeneration, coatings for bone implants, and drug delivery systems. Finally, the future perspectives and challenges in the development of this field are discussed. Thiolation modification strategies provide a platform for developing new ideas and methods for designing nanomaterials for BTE and are expected to accelerate the development and clinical translation of novel bone repair materials.
Tissue engineering (TE) aims to provide personalized solutions for tissue loss caused by trauma, tumors, or congenital defects. While traditional methods like autologous and homologous tissue transplants face challenges such as donor shortages and risk of donor site morbidity, TE provides a viable alternative using scaffolds, cells, and biologically active molecules. Textiles represent a promising scaffold option for both in-vitro and in-situ TE applications.
Textile engineering is a broad field and can be divided into fiber-based textiles and yarn-based textiles. In fiber-based textiles the textile fabric is produced in the same step as the fibers (e.g. non-wovens, electrospun mats and 3D-printed). For yarn-based textiles, yarns are produced from fibers or filaments first and then, a textile fabric is produced (e.g. woven, weft-knitted, warp-knitted and braided fabrics).
The selection of textile scaffold technology depends on the target tissue, mechanical requirements, and fabrication methods, with each approach offering distinct advantages. Braided scaffolds, with their high tensile strength, are ideal for load-bearing tissues like tendons and ligaments, while their ability to form stable hollow lumens makes them suitable for vascular applications. Weaving, weft-, and warp-knitting provide tunable structural properties, with warp-knitting offering the greatest design flexibility. Spacer fabrics enable complex 3D architecture, benefiting applications such as skin grafts and multilayered tissues. Electrospinning, though highly effective in mimicking the ECM, is structurally limited. The complex interactions between materials, fiber properties, and textile technologies allows for scaffolds with a wide range of morphological and mechanical characteristics (e.g., tensile strength of woven textiles ranging from 0.64 to 180.4 N/mm²). With in-depth knowledge, textiles can be tailored to obtain specific mechanical properties as accurately as possible and aid the formation of functional tissue. However, as textile structures inherently differ from biological tissues, careful optimization is required to enhance cell behavior, mechanical performance, and clinical applicability.
This review is intended for TE experts interested in using textiles as scaffolds and provides a detailed analysis of the available options, their characteristics and known applications. For this, first the major fiber formation methods are introduced, then subsequent used automated textile technologies are presented, highlighting their strengths and limitations. Finally, we analyze how these textile and fiber structures are utilized in TE, organized by the use of textiles in TE across major organ systems, including the nervous, skin, cardiovascular, respiratory, urinary, digestive, and musculoskeletal systems.
Osteoporosis, characterized by low bone mass and high fracture risk, challenges orthopedic implant design. Conventional 3D‐printed Ti6Al4V scaffolds are mechanically robust but suffer from poor bone regeneration in osteoporotic patients due to stress shielding and cellular senescence. In this study, a functionalized 3D‐printed Ti6Al4V “Cell Climbing Frame” is developed, aiming to adapt to the mechanical microenvironment of osteoporosis, effectively recruit and support the adhesion and growth of autologous bone marrow mesenchymal stem cells (BMSCs), while rejuvenating senescent cells for improved bone regeneration. Inspired by marine sponges, the processing accuracy limitations of selective laser melting (SLM) technology is broke through innovatively constructing a hierarchical porous structure with macropores and micropores nested within each other. Results demonstrate that the unique hierarchical porous scaffold reduces the elastic modulus, facilitates blood penetration, and enhances cell adhesion and growth. Further surface functionalization with E7 peptides and exosomes promotes the attraction and rejuvenation of BMSCs and boosts migration, proliferation, and osteogenic differentiation in vitro. In vivo, the functionalized “Cell Climbing Frame” accelerates bone repair in osteoporotic rats, while delaying surrounding bone loss, enabling robust multi‐stage osseointegration. This innovation advances 3D‐printed regenerative implants for osteoporotic bone repair.
3D printing is a leading technique for fabricating tissue engineering scaffolds that facilitate native cellular behavior. Engineering scaffolds to possess functional properties like electronic conductivity is the first step toward integrating new technological capabilities like stimulating or monitoring cellular activity beyond the traditionally presented biophysical and biochemical cues. However, these bioelectronic scaffolds have been largely underdeveloped since the majority of electrically conducting materials possess high stiffness values outside the physiological range and that may negatively impact desired cell behavior. Here, methods of 3D printing poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogel scaffolds and techniques to achieve stiffness relevant to many soft tissues (<100 kPa) are reported. Structures are confirmed as ideal tissue scaffolds by maintaining biostability, promoting high cell viability, as well as appropriate cell morphology and proliferation. These findings present a customizable 3D platform that provides favorable soft cellular microenvironments and this is envisioned to be adaptable to several bioelectronic applications.
Addressing irregular bone defects is a formidable clinical challenge, as traditional scaffolds frequently fail to meet the complex requirements of bone regeneration, resulting in suboptimal healing. This study introduces a novel 3D-printed magnesium scaffold with hierarchical structure (macro-, meso-, and nano-scales) and tempered degradation (microscale), intricately customized at multiple scales to bolster bone regeneration according to patient-specific needs. For the hierarchical structure, at the macroscale, it can feature anatomic geometries for seamless integration with the bone defect; The mesoscale pores are devised with optimized curvature and size, providing an adequate mechanical response as well as promoting cellular proliferation and vascularization, essential for natural bone mimicry; The nanoscale textured surface is enriched with a layered double hydroxide membrane, augmenting bioactivity and osteointegration. Moreover, microscale enhancements involve a dual-layer coating of high-temperature oxidized film and hydrotalcite, offering a robust shield against fast degradation. Eventually, this scaffold demonstrates superior geometrical characteristics, load-bearing capacity, and degradation performance, significantly outperforming traditional scaffolds based on in vitro and in vivo assessments, marking a breakthrough in repairing customized bone defects.
3D printed titanium scaffold has promising applications in orthopedics. However, the bioinert titanium presents challenges for promoting vascularization and tissue growth within the porous scaffold for stable osteointegration. In this study, a modular porous titanium scaffold is created using 3D printing and a gradient‐surface strategy to immobilize QK peptide on the surface with a bi‐directional gradient distribution. This design featured high peptide density in the interior and low peptide density on both ends, aiming to induce cell migration from ends to interior and subsequently enhance vascularization and osteointegration within the scaffold. In vitro results showed that besides the inherent bioactivity, the gradient distribution of QK positively correlated with endothelial cell migration and promoted angiogenesis. In vivo assay was performed by a segmental bone defect model in rabbit and a spine repair model in sheep. Various staining and Micro‐CT results demonstrated that compared to that with uniformly QK‐functionalized surface, the scaffold with bi‐directional gradient QK‐functionalized surface (Ti‐G) significantly encouraged new tissue growth toward the interior of the scaffold, subsequently facilitated angiogenesis and osteointegration. This study provides an effective strategy for enhancing the bioactivity of peptide‐functionalized scaffolds through the concept of bi‐directional gradients, and holds potential for various 3D printed scaffolds.
Effective treatment of bone diseases is quite tricky due to the unique nature of bone tissue and the complexity of the bone repair process. In combination with biological materials, cells and biological factors can provide a highly effective and safe treatment strategy for bone repair and regeneration, especially based on these multifunctional hydrogel interface materials. However, itis still a challenge to formulate hydrogel materials with fascinating properties (e.g., biological activity, controllable biodegradability, mechanical strength, excellent cell/tissue adhesion, and controllable release properties) for their clinical applications in complex bone repair processes. In this review, we will highlight recent advances in developing functional interface hydrogels. We then discuss the barriers to producing of functional hydrogel materials without sacrificing their inherent properties, and potential applications in cartilage and bone repair are discussed. Multifunctional hydrogel interface materials can serve as a fundamental building block for bone tissue engineering.
The porous polymer is a common and fascinating category within the vast family of porous materials. It offers valuable features such as sufficient raw materials, easy processability, controllable pore structures, and adjustable surface functionality by combining the inherent properties of both porous structures and polymers. These characteristics make it an effective choice for designing functional and advanced materials. In this review, the structural features, processing techniques and application fields of the porous polymer are discussed comprehensively to present their current status and provide a valuable tutorial guide and help for researchers. Firstly, the basic classification and structural features of porous polymers are elaborated upon to provide a comprehensive analysis from a mesoscopic to macroscopic perspective. Secondly, several established techniques for fabricating porous polymers are introduced, including their respective basic principles, characteristics of the resulting pores, and applied scopes. Thirdly, we demonstrate application research of porous polymers in various emerging frontier fields from multiple perspectives, including pressure sensing, thermal control, electromagnetic shielding, acoustic reduction, air purification, water treatment, health management, and so on. Finally, the review explores future directions for porous polymers and evaluates their future challenges and opportunities.
In the present investigation, the influence of compression rate and pore size distribution on the compression behavior of additively produced Fe3Si microporous specimens is analyzed. The specimens with uniform and graded porosities are created using computer-aided design and manufactured through laser powder bed fusion techniques. Both the uniform microporous and graded microporous specimens demonstrate the same average porosity of 70%. The sole distinction between the two specimen categories lies in the distribution of pore sizes. The uniform porosity and graded porosity Fe3Si specimens reveal four distinct regions in the compression force–displacement curves. The transition between the elastic and plastic regions is noted to be either smooth or abrupt. At lower strain rates (0.0001 s-1), the energy absorbed per unit mass is greater for the uniform Fe3Si microporous specimens. Conversely, at higher strain rates (0.1 s-1), the energy absorbed per unit mass is greater for the graded Fe3Si microporous specimens. The uniformly porous Fe3Si specimens exhibit a higher plateau force compared to the graded porosity Fe3Si specimens. A delayed onset of densification in uniform porosity specimens is observed in comparison with graded porosity specimens. The compression velocity is noted to influence the deformation behavior of the uniformly porous specimens but not the graded porosity specimens.
The implant surface chemistry and topography are primary factors regulating the success and survival of bone scaffold. Surface modification is a promising alternative to enhance the biocompatibility and tissue response to augment the osteogenic functionalities of polyesters like PLA. The study employed the synergistic effect of alkaline hydrolysis and polydopamine (PDA) functionalization to enhance the cell–material interactions on 3D printed polylactic acid (PLA) scaffold. Comprehensive characterization of the modified PLA highlights the improvements in the physical, chemical and cell–material interactions upon two-step surface modification. The X-ray photoelectron spectroscopy (XPS) analysis substantiated enhanced PDA deposition with a ∼8.2% increase in surface N composition after surface etching due to homogeneous PDA deposition compared to the non-etched counterpart. The changes in surface chemistry and morphology upon dual surface modification complemented the human osteoblast (HOS) attachment and proliferation, with distinct cell morphology and spreading on PDA coated etched PLA (Et-PLAPDA) scaffolds. Moreover, substantial improvement in osteogenic differentiation of UMR-106 cells on etched PLA (Et-PLA) and Et-PLAPDA highlights the suitability of alkali etching-mediated PDA deposition to improve mineralization on PLA. Overall, the present work opens insights to modify scaffold surface composition, topography, hydrophilicity and roughness to regulate local cell adhesion to improve the osteogenic potential of PLA.
This study focuses on the development of nickel-free stainless-steel nanocomposites with porosities tailored for surgical implants and biological applications. Alloy F2581 (Fe–17Cr–10Mn–3Mo–0.4Si–0.5N–0.2C wt%), modified by replacing Mo with metals such as Al, Cu, Ti, and W, was successfully fabricated via a solid-state reaction method. X-ray diffraction analysis revealed a significant alteration in the crystal phase, accompanied by the formation of nanostructures, including nanowires, square nanotubes, wave-like configurations reminiscent of a growing clover farm, and nanofibers. The particle sizes of these structures were determined to be 73, 27.2, 76 and 98.5 nm for Al, Cu, Ti, and W ions, respectively, indicating a distribution of nanopores. Biological evaluation of adult male Albino rats after exposure to single intraperitoneal doses of various concentrations (10, 20, and 50 mg kg⁻¹ wt%) were assessed with testing alloys (Cu, Al, W, and Ti, respectively). Over a subacute period lasting 60 days, a comprehensive evaluation of biological responses, including hepatic function, renal performance, oxidative and/or nitrosative stress parameters, and the levels of serum immune modulators was conducted. Notably, low doses elicited negligible immune responses, higher doses, barring copper, induced notable reactions. Interestingly, aluminum demonstrated optimization within biological settings, alongside titanium and tungsten. These findings highlight the applicability of copper and tungsten for medical implantation and biological applications under controlled circumstances, particularly at lower dosage levels.
In a previous study, it was found that annealing heat treatment significantly eliminated the residual stress in 316L porous scaffolds with negative re-entrant hexagonal honeycomb (NRHH) prepared by selective laser melting (SLM), but at the same time reduced the mechanical properties and corrosion resistance. To improve the performance of scaffolds while eliminating residual stress, this paper focuses on the heat treatment cooling mode and explores the effects of heat treatment cooling mode on microstructure evolution and phase transformation, residual stress, mechanical properties, and corrosion resistance to seek a suitable heat treatment process. For this purpose, the SLM-prepared porous scaffolds were held at 800 and 950°C for 2 h, respectively, and then three different cooling methods, water-cooling, air-cooling, and furnace-cooling, were used. The results of the microstructural analysis confirm that the cooling mode of heat treatment significantly affects the microstructural evolution and phase transformation. The slow cooling process is more favorable for the release of residual stresses. The release of residual stresses and grain coarsening after heat treatment led to a decrease in the microhardness of the scaffolds. However, the ferrite phase content increased after water-cooling heat treatment at 800°C, and the microhardness values of the scaffolds increased by 0.89% and 5.15% in the two planes, respectively. The modulus of elasticity of the scaffold increases with the cooling rate, and the maximum stress value decreases with the cooling rate. The corrosion resistance deteriorates with the slowing down of the cooling rate of heat treatment and the increase in temperature, and it is more favorable to resist corrosion after 800°C water-cooling heat treatment.
Magnesium (Mg) alloys have gained recognition as revolutionary biomaterials, owing to their inherent degradability, favorable biocompatibility and mechanical properties. Additive manufacturing (AM) provides high design flexibility and enables the creation of implants with personalized complex shapes and internal porous structures tailored to individual anatomical and functional needs. Particularly, laser powder bed fusion (LPBF), one prevalent AM technique, utilizes a fine laser beam as heat source and results in tiny molten pool with extremely fast cooling rate, which effectively restricts grain growth, inter-metallic precipitation and macroscopic segregation, thus facilitating the fabrication of high-performance metal parts. This review critically assesses the significance of biodegradable Mg alloys and investigates the feasibility of utilizing LPBF for Mg alloys applications in biomedical field. Detailed discussions on LPBF-processed biomedical Mg alloys parts cover process parameters, microstructure, metallurgical defects, and properties like mechanical performance, corrosion behavior, and biological response in both as-built and post-processed states. Additionally, suggestions for advancing knowledge in LPBF of biodegradable Mg alloys for biomedical applications are highlighted to propel further research and development in this field.
Constructing scaffolds with the desired structures and functions is one of the main goals of tissue engineering. Three-dimensional (3D) bioprinting is a promising technology that enables the personalized fabrication of devices with regulated biological and mechanical characteristics similar to natural tissues/organs. To date, 3D bioprinting has been widely explored for biomedical applications like tissue engineering, drug delivery, drug screening, and in vitro disease model construction. Among different bioinks, photocrosslinkable bioinks have emerged as a powerful choice for the advanced fabrication of 3D devices, with fast crosslinking speed, high resolution, and great print fidelity. The photocrosslinkable biomaterials used for light-based 3D printing play a pivotal role in the fabrication of functional constructs. Herein, this review outlines the general 3D bioprinting approaches related to photocrosslinkable biomaterials, including extrusion-based printing, inkjet printing, stereolithography printing, and laser-assisted printing. Further, the mechanisms, advantages, and limitations of photopolymerization and photoinitiators are discussed. Next, recent advances in natural and synthetic photocrosslinkable biomaterials used for 3D bioprinting are highlighted. Finally, the challenges and future perspectives of photocrosslinkable bioinks and bioprinting approaches are envisaged.
Regenerative medicine is a rapidly advancing field to revolutionize healthcare by offering innovative solutions for repairing or replacing damaged tissues and organs. By addressing significant challenges associated with conventional therapies—such as the shortage of donor organs and complications related to immune rejection—regenerative medicine provides a hopeful alternative for patients suffering from chronic diseases and injuries. This review outlines the urgent need for regenerative medicine to tackle prevalent issues like chronic conditions, organ scarcity, and injury recovery through approaches like stem cell therapy and tissue engineering. Key therapies currently available in the market, such as Carticel and Celution, utilize both autologous and allogeneic cells to promote healing and tissue regeneration. Recent breakthroughs showcase the transformative potential of regenerative medicine, with notable successes including stem cell therapies for spinal cord injuries, 3D-printed skin grafts for burn victims, and the development of lab-grown organs. These advancements highlight regenerative medicine's capability to enhance patient outcomes significantly. Looking ahead, the future of regenerative medicine lies in the personalization of therapies, advanced biomaterials, and cutting-edge technologies like 3D bioprinting. These innovations will enable the creation of complex and functional tissues tailored to individual patients. As research continues to progress, regenerative medicine holds the promise of offering long-term, transformative solutions for a wide range of medical conditions..
Bone tissue engineering (BTE) has emerged as a promising approach for the regeneration and repair of bone defects caused by trauma, disease, or aging. This review provides an overview of recent advancements in BTE, with a focus on the development and application of biomaterial‐based scaffolds, including natural (e.g., collagen, chitosan), synthetic (e.g., polylactic acid [PLA], polycaprolactone [PCL]), and composite materials (e.g., hydroxyapatite‐based composites). It discusses their properties, benefits, and limitations. Additionally, this review examines innovative fabrication strategies such as 3D printing, electrospinning, and freeze‐drying, which enhance scaffold customization and performance. This review aims to provide insights into future directions of BTE research and its potential applications in regenerative medicine. Functionalization strategies, including surface modifications, coating, and the incorporation of growth factors and cells, are reviewed for their roles in improving scaffold bioactivity. In vivo and in vitro research have demonstrated the therapeutic promise of these scaffolds, while current clinical trials offer insights into their translational use. Challenges facing the translation of these technologies into clinical practice are also highlighted.
Composite materials, made by mixing two or more chemically or physically different components, have unique properties. Recent progress in composite biomaterials research has revolutionized, expanding treatment opportunities and improving patient outcomes. These materials offer mechanical support to biological tissues and exhibit biocompatibility and nontoxicity, facilitating their manipulation into intricate structures and shapes. Advances in manufacturing techniques have further influenced the evolution of composite biomaterials. The domain of composite biomaterials has seen the emergence of various materials with unique properties and applications. Natural and synthetic polymers have been fabricated into composite biomaterials for tissue engineering and drug delivery. Ceramics and metals have been tailored for bone tissue engineering and orthopedic implants. Notably, composite materials are pivotal in dental implants with esthetic appeal, crafting durable yet lightweight structures that endure physiological stresses. Composite scaffolds in tissue engineering, composed of biodegradable polymers reinforced with nanomaterials, provide the necessary framework for new tissue growth.
The development of bioceramic materials is at the forefront of health-related issues in many countries. Arguably, research into ceramic biomaterials has reached a level of involvement and sophistication comparable only to electronic ceramics. Despite the fact that calcium phosphate-based coatings on hip, knee and dental implants have a long history of clinical success the quest of improving the longevity of implants and to impart them with better physiological properties is high up on the agenda of numerous research groups around the world. Coating the stem of modern cementless endoprostheses with a layer of plasma-sprayed hydroxyapatite improves the ingrowth of bone cells and thus assists in anchoring the implant to the cortical bone matter. However, since the high temperature process of plasma spraying leads to incongruent melting and thus thermal decomposition of the hydroxyapatite, knowledge of the complex transformation sequence is essential to design coatings with optimum stability and hence biological performance. This contribution reviews recent research into the thermal history of thermally sprayed calcium phosphate coatings as well as their in vitro behavior in contact with simulated body fluid.
Biomimetic scaffolds mimic important features of the extracellular matrix (ECM) architecture and can be finely controlled at the nano- or microscale for tissue engineering. Rational design of biomimetic scaffolds is based on consideration of the ECM as a natural scaffold; the ECM provides cells with a variety of physical, chemical, and biological cues that affect cell growth and function. There are a number of approaches available to create 3D biomimetic scaffolds with control over their physical and mechanical properties, cell adhesion, and the temporal and spatial release of growth factors. Here, an overview of some biological features of the natural ECM is presented and a variety of original engineering methods that are currently used to produce synthetic polymer-based scaffolds in pre-fabricated form before implantation, to modify their surfaces with biochemical ligands, to incorporate growth factors, and to control their nano- and microscale geometry to create biomimetic scaffolds are discussed. Finally, in contrast to pre-fabricated scaffolds composed of synthetic polymers, injectable biomimetic scaffolds based on either genetically engineered- or chemically synthesized-peptides of which sequences are derived from the natural ECM are discussed. The presence of defined peptide sequences can trigger in situ hydrogelation via molecular self-assembly and chemical crosslinking. A basic understanding of the entire spectrum of biomimetic scaffolds provides insight into how they can potentially be used in diverse tissue engineering, regenerative medicine, and drug delivery applications.
Recent exciting findings of the biological interactions of graphene materials have shed light on potential biomedical applications of graphene-containing composites. Fabrication of bulk composites in particular nanostructured coatings from nanosize particles/sheets yet remains elusive. Here we report hydroxyapatite (HA) and HA–graphene nanosheet (GN) composites synthesized by liquid precipitation approach and following coating deposition by vacuum cold spraying. The HA–GN composite coatings retained intact nano-structural features of both HA and GN. The impact of the HA–GN particles during coating formation created layered coating structures and mechanical interlocking was achieved by even distribution of GN. In vitro cell culture assessment showed that filopodia of osteoblast cells inclined to move towards and got anchored by GN. Further observation by electron microscopy of adsorption of fibronectin on GN by negative staining showed fast adsorption of fibronectin in unfolded shape with the length of ∼100–135 nm. This presumably accounts for the enhanced spreading and subsequent proliferation of the cells on the GN-containing coatings. The strategy of depositing the novel HA–GN composite coatings gives bright insight into potential biomedical applications of the composites.
Mechanical properties of the extracellular matrix (ECM) play an essential role in cell fate determination. To study the role of mechanical properties of ECM in stem cell-mediated bone regeneration, we used a 3D in vivo ossicle model that recapitulates endochondral bone formation. Three-dimensional gelatin scaffolds with distinct stiffness were developed using 1-Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) mediated zero-length crosslinking. The mechanical strength of the scaffolds was significantly increased by EDC treatment, while the microstructure of the scaffold was preserved. Cell behavior on the scaffolds with different mechanical properties was evaluated in vitro and in vivo. EDC-treated scaffolds promoted early chondrogenic differentiation, while it promoted both chondrogenic and osteogenic differentiation at later time points. Both micro-computed tomography and histologic data demonstrated that EDC-treatment significantly increased trabecular bone formation by transplanted cells transduced with AdBMP. Moreover, significantly increased chondrogenesis was observed in the EDC-treated scaffolds. Based on both in vitro and in vivo data, we conclude that the high mechanical strength of 3D scaffolds promoted stem cell mediated bone regeneration by promoting endochondral ossification. These data suggest a new method for harnessing stem cells for bone regeneration in vivo by tailoring the mechanical properties of 3D scaffolds.
Cancer therapeutics are developed through extensive screening; however, many therapeutics evaluated with 2D in vitro cultures during pre-clinical trials suffer from lower efficacy in patients. Replicating the in vivo tumor microenvironment in vitro with three-dimensional (3D) porous scaffolds offers the possibility of generating more predictive pre-clinical models to enhance cancer treatment efficacy. We developed a chitosan and hyaluronic acid (HA) polyelectrolyte complex 3D porous scaffold and evaluated its physical properties. Chitosan-HA (C-HA) scaffolds had a highly porous network. C-HA scaffolds were compared to 2D surfaces for in vitro culture of U-118 MG human glioblastoma (GBM) cells. C-HA scaffold cultures promoted tumor spheroid formation and increased stem-like properties of GBM cells as evidenced by the upregulation of CD44, Nestin, Musashi-1, GFAP, and HIF-1α as compared with 2D cultures. Additionally, the invasiveness of GBM cells cultured in C-HA scaffolds was significantly enhanced compared to those grown in 2D cultures. C-HA scaffold cultures were also more resistant to chemotherapy drugs, which corresponded to the increased expression of ABCG2 drug efflux transporter. These findings suggest that C-HA scaffolds offer promise as an in vitro GBM platform for study and screening of novel cancer therapeutics.
Rapid endothelialization by surface coverage is considered as a way to increase blood compatibility of the vascular stent and reduce smooth muscle cell (SMC) mediated restenosis. Coatings on 316L stainless steels with different wettabilities and similar topographies were obtained through sol–gel process by regulating the proportions of tetraethoxysilane (TEOS) and methyltriethoxysilane (MTES). Adhesion and proliferation of vascular endothelial cells (EC) and SMC on these substrates have been evaluated by cell numbers, cell morphology, and expression of cytoskeletal protein. Results showed that EC and SMC responded differently to the coated surfaces. Enhanced endothelialization of bare 316L was found at the moderately hydrophilic coating (contact angle 45.3°) which exhibited effective inhibition of SMC and negligible influence on EC. These results are expected to lay foundation for the solution of the vascular restenosis which was mainly derived from the hyperplasia of SMC.
Based on a binary Ti-26Nb (at%) alloy, Ti-(26-z)at% Nb-(z)at% Zr (z=2, 6, 8 and 10) alloys via equiatomic substitution of Nb by Zr are formulated. Influence of equiatomic Zr/Nb substitution on microstructure evolution, mechanical properties and deformation mechanism of the superelastic Ti-Nb-Zr alloy are investigated. Experimental results show that the phase constitution is single beta phase or beta/omega(ath) phase at 0 < Zr/Nb < 0.35 since the measured Ms temperature is maintained at around 250 K. The two-phase microstructure consist of alpha " martensite and beta phase is obtained at Zr/Nb ratio > 0.4 due to the attenuation of beta stabilizing effect of Zr, which is related closely to the Nb content in ternary Ti-Nb-Zr alloys. The mechanism of the superelastic behavior alters gradually from reversible beta/alpha " martensitic transformation to rearrangement of pre-existing alpha " martensites as a function of Zr/Nb ratio increase. At Zr/Nb=0.3, the alloy of corresponding composition exhibits the best superelasticity and combined mechanical performance. A coefficient of Delta T (Delta T=T-beta-Ms) is proposed to understand the experimental results by evaluating the beta instability of Ti-Nb-Zr alloys. (c) 2012 Elsevier B.V. All rights reserved.
A Complicated Scaffold, Simply
Materials with tailored pore structures can be useful as catalysis supports and for lightweight materials. When preparing medical scaffolds, restrictive preparation conditions have to be met, which can prohibit multistep preparation procedures. Sai et al. (p. 530 ) describe a method for making porous polymers containing both relatively large (several microns) interconnecting pores and a second population of ∼ tens of nanometer pores. The process exploits spinodal decomposition of a block copolymer blended with small-molecule additives and requires a simple washing step with water, methanol, or ethanol.
The physiological microenvironment of the stem cell niche, including the three factors of stiffness, topography, and dimension, is crucial to stem cell proliferation and differentiation. Although a growing body of evidence is present to elucidate the importance of these factors individually, the interaction of the biophysical parameters of the factors remains insufficiently characterized, particularly for stem cells. To address this issue fully, we applied a micro-fabricated polyacrylamide hydrogel substrate with two elasticities, two topographies, and three dimensions to systematically test proliferation, morphology and spreading, differentiation, and cytoskeletal re-organization of rat bone marrow mesenchymal stem cells (rBMSCs) on twelve cases. An isolated but not combinatory impact of the factors was found regarding the specific functions. Substrate stiffness or dimension is predominant in regulating cell proliferation by fostering cell growth on stiff, unevenly dimensioned substrate. Topography is a key factor for manipulating cell morphology and spreading via the formation of a large spherical shape in a pillar substrate but not in a grooved substrate. Although stiffness leads to osteogenic or neuronal differentiation of rBMSCs on a stiff or soft substrate, respectively, topography or dimension also plays a lesser role in directing cell differentiation. Neither an isolated effect nor a combinatory effect was found for actin or tubulin expression, whereas a seemingly combinatory effect of topography and dimension was found in manipulating vimentin expression. These results further the understandings of stem cell proliferation, morphology, and differentiation in a physiologically mimicking microenvironment.
The present paper is focused on a study regarding the possibility of obtaining hydroxyapatite-silver nanoparticle coatings on porous polyurethane scaffold. The method applied is based on a combined strategy involving hydroxyapatite biomimetic deposition on polyurethane surface using a Supersaturated Calcification Solution (SCS), combined with silver ions reduction and in-situ crystallization processes on hydroxyapatite-polyurethane surface by sample immersing in AgNO3 solution. The morphology, composition and phase structure of the prepared samples were characterized by scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX), X-ray diffraction (XRD), UV-Vis spectroscopy and X-ray photoelectron spectroscopy (XPS) measurements. The data obtained show that a layer of hydroxyapatite was deposited on porous polyurethane support and the silver nanoparticles (average size 34.71 nm) were dispersed among and even on the hydroxyapatite crystals. Hydroxyapatite/polyurethane surface acts as a reducer and a stabilizing agent for silver ions. The surface plasmon resonance peak in UV-Vis absorption spectra showed an absorption maximum at 415 nm, indicating formation of silver nanoparticles. The hydroxyapatite-silver polyurethane scaffolds were tested against Staphylococcus aureus and Escherichia coli and the obtained data were indicative of good antibacterial properties of the materials.
Relevant mechanical properties of bone The mechanical properties of bone material are determined by the relative amounts of its 3 major constituents: mineral, water, and organics (mainly type I collagen); by the quality of these components; and by how the resulting material is arranged in space. For our purposes, the mechanical properties of bone can be summed up as follows: modulus of elasticity, yield stress and yield strain, post-yield stress and post-yield strain, and the total area under the stress-strain curve. Also important are some fracture mechanics properties, but these are not discussed here. A typical tensile stress-strain curve for a bone specimen is shown in Fig. 1. The modulus of elasticity shows how stiff the bone material is. Indeed, stiffness is the prime property of bone, distinguishing it from tendon, which has much less tensile stiffness, almost no shear stiffness, but which is nearly as strong and is much tougher. Yield stress and strain determine how much energy can be absorbed before irreversible changes take place. Post-yield stress and strain determine mainly how much energy can be absorbed after yield but before fracture. Irreversible changes take place at yield, caused by microdamage. The total area under the stress-strain curve is equivalent to the work that must be done per unit volume on the specimen before it breaks. Fracture mechanics properties show the extent to which bone is resistant to crack initiation and to crack travel (which are different things and governed by somewhat different features). In fact, crack travel resistance is given rather well by post-yield stress and strain.
A hydrothermal approach was used to prepare large-scale, aligned ultrafine bone-like apatite nanorod arrays on electrospun nylon 6 (N6) nanofibers using simulated body fluid. X-ray diffraction, field emission scanning electron microscopy, X-ray photoelectoron spectroscopy and Fourier transform infrared spectroscopy (FTIR) were used to study structural features and the chemical composition of the synthesized biocomposites. Apatite nanorods of ∼60 nm length and 10-17 nm width were uniformly distributed onto the surface of individual nanofibers. Deposition of apatite on pristine nanofiber surfaces at an initial pH of 6.5-7.5 accelerated when the reaction time was extended. Nanofibers and the ultrathin fibers that generated a spiderweb-like structure after coating maintained a unique fibrous morphology. FTIR and thermal analysis demonstrated strong intermolecular hydrogen bonding between the polymer molecules and mineralized compounds from the hydrothermal reaction. Our results also indicated a change in the chain conformation of the N6 backbone from the fabrication process. Thus, our investigation found that the hydrothermal process did not notably degrade the N6, but transformed it from a metastable γ-form to thermodynamically stable chain conformation (α-form). Further, the biological response induced by the surface modifications of N6 nanofibers was studied by in vitro cell culture with MC3T3-E1 osteoblasts cells.
Biodegradability is a big advantage of magnesium-based materials in biomedical applications such as bone fixation, cardiovascular stents, and even stomach trauma repair. Different from other metals such as stainless steels and Ti alloys, the interface between the Mg-based implants and biological environment is dynamic. In order to improve the surface properties to allow better and more expeditious adaptation to the physiological surroundings, it is imperative to design and construct a surface to satisfy multiple clinical requirements such as mechanical strength, biocompatibility, and degradation rate. This paper reviews recent work pertaining to surface modification of Mg-based biomaterials with emphasis on surface coatings and ion implantation. The biodegradation behavior and related mechanism in the physiological environment after surface modification are also described. Surface modification is a promising means to elevate the performance of Mg-based biomaterials and expected to be extensively applied to surface design of biomaterials.
Ti-based alloys are widely used in orthopedic implants because of their excellent mechanical properties and biocompatibility. However, in the complex physiological environment and influenced by other factors like cyclic loading, these implants can lose their natural properties and become incompatible or cyto-toxic to the body tissues and cells. Two of the causes are the deteriorated mechanical properties in this dynamic environment and the effects of by-products stemming from corrosion. In serious cases, implant failure results. Nano architectures on the surface of these alloys can improve the in vivo and in vitro biocompatibility of these alloys. This paper reviews recent progress pertaining to the design and construction of nano surface architectures on Ti-based alloys and their effects on the mechanical properties and corrosion resistance in the simulated physiological environment.
During the past decade, important advances have been made in the understanding of the hydrolytic degradation characteristics of aliphatic polyesters derived from lactic acid (LA) and glycolic acid (GA). Degradation of large poly(LAGA) (PLAGA) polymers is autocatalyzed by carboxyl end groups initially present or generated upon ester bond cleavage. Faster internal degradation and degradation-induced morphological and compositional changes are three of the most important findings deduced from the behaviors of various PLAGA polymers. This review presents the state of the art in this domain. The research efforts are focused on detailing the degradation mechanism and the effects of various factors on the degradation of PLAGA polymers. An attempt is also made to elaborate a scheme that can be used to predict degradation characteristics of these polymers from their initial composition and morphology. © 1999 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 48: 342–353, 1999
Antimicrobial hydroxyapatite (HAp) nanoparticles with different concentrations (0, 3, and 6 mol%) of zinc were prepared by the ultrasonication process. The prepared nanoparticles and chitosan (CTS) composite were coated on 316L stainless steel implant by spin coating technique. The powder samples were characterised by particle size analyser, X-ray fluorescence, and X-ray diffraction studies. The morphology of the coating was investigated by scanning electron microscopy. The diameter of the particle size decreased with increase in the concentration of zinc in HAp structure. The structure of the coated implant was found to be uniform without any cracks and pores. Antimicrobial activity of the composites against Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumonia, Salmonella typhi and Pseudomonas aeruginosa was analysed. The results showed that the increase in the concentration of zinc enhances the antimicrobial properties of 316L stainless steel implant. The stability of the implant in physiological environment was characterised by electrochemical impedance spectroscopy and polarisation analysis. The higher concentration of the ZnHAp/CTS composite shows higher corrosion resistance than that of the HAp/CTS-coated implant. This study shows that the coating provides corrosion resistance to the stainless steel substrate in simulated body fluid (SBF). The in vitro bioactivity study of the coated samples immersed in SBF
solution confirms the formation of bone-like apatite layer on the surface of the implant. Thus, highly biocompatible ZnHAp/CTS-coated materials could be very useful in the long-term stability of the biomedical applications.
Coated layers of biologically active molecules on synthetic biomaterials and biomedical devices can promote a variety of desirable biological reactions by the host body or the biological medium, such as cell and tissue attachment or deterring bacterial biofilm formation. Such coated layers should be immobilised covalently in order to avoid competitive displacement phenomena, and the use of surface-activating plasmas or plasma polymer interlayers with suitable chemical surface groups has proved to be very convenient means of grafting bioactive molecules onto solid materials surfaces. We review selected work on the covalent immobilisation of proteins and peptides onto solid biomaterial surfaces and describe efforts towards plasma methods that allow biomolecules to be covalently captured in a single step. After reviewing a number of approaches, we discuss in more detail the use of plasma polymer interlayers that possess aldehyde or epoxide surface groups; these groups react readily with amine groups on proteins and peptides without undesirable side reactions, and avoid other issues such as crosslinking. We also emphasise the importance of detailed surface analysis to verify that covalent grafting has indeed taken place, and to assess the surface density of grafted molecules. With suitably chosen peptides or proteins, such covalently grafted layers can support the surface attachment of delicate cells, or combat bacterial biofilm formation.
Properties of materials -- Classes of materials used in medicine -- Some background concepts -- Host reactions to biomaterials and their evaluation -- Biological testing of biomaterials -- Degradation of materials in the biological environment -- Application of materials in medicine, biology, and artificial organs -- Tissue engineering -- Implants, devices, and biomaterials: issues unique to this field -- New products and standards -- Perspectives and possibilities in biomaterials science
This study discusses manufacturing of metallic biomaterials by means of powder metallurgy with consideration for their unquestionable advantages, i.e. opportunities of obtaining materials with controllable porosity. The paper focuses on properties of 316L stainless steel obtained using the method of powder metallurgy with respect to compacting pressure and sintering atmosphere. All the specimens were compacted at 700, 400 and 225 MPa, and sintered at 1250 °C. In order to analyze the sintering atmosphere, three different media were used: dissociated ammonia, hydrogen and vacuum. The study covered sintering density, porosity, microstructure analysis and corrosion resistance. The proposed method of powder metallurgy allowed for obtaining materials with predictable size and distribution of pores, depending on the parameters of sinter preparation (compaction force, sinter atmosphere). High corrosion resistance of the materials (sintering in the atmosphere of hydrogen and in vacuum) and high porosity in the sinters studied offer opportunities for using them for medical purposes.
With tissue engineering we can create biological substitutes to repair or replace failing organs or tissues. Synthetic biopolymer-based nanocomposites are of interest for use in tissue engineering scaffolds due to their biocompatibility and adjustable biodegradation kinetics. The most often utilized synthetic biopolymers for three dimensional scaffolds in tissue engineering are saturated poly(α-hydroxy esters), including poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic acid-co-glycolic acid) (PLGA), and poly(ɛ-caprolactone) (PCL). To enhance the mechanical properties and cellular adhesion and proliferation, the incorporation of nanoparticles (e.g., apatite component, carbon nanostructures and metal nanoparticles) has been extensively investigated. At the same time, current research is focused on the interaction between stromal cells and biopolymer interfaces. In this review, current research trends in nanocomposite materials for tissue engineering, including strategies for fabrication of nanocomposite scaffolds with highly porous and interconnected pores are presented. The results of the in vitro cell culture analysis of the cell–scaffold interaction using the colonization of mesenchymal stem cells (MSCs) and degradation of the scaffolds in vitro are also discussed.
Plasma immersion ion implantation and deposition (PIII&D) is conducted to modify the corrosion behavior of Mg–Nd–Zn–Zr alloy. A diamond-like carbon film (DLC) with a thickness of about 200 nm is formed on the surface after acetylene PIII&D and the resulting corrosion resistance in the 0.9 wt% NaCl solution is significantly improved. The corrosion mechanism is discussed from the perspective of random defects in the DLC film.
A systematic analysis of results available from in vitro, in vivo, and clinical trials on the effects of biocompatible CaP coatings is presented. An overview of the most frequently used methods to prepare CaP-based coatings was conducted. Dense, homogeneous, highly adherent, and biocompatible CaP or hybrid organic/inorganic CaP coatings with tailored properties can be deposited. It has been demonstrated that CaP coatings have a significant effect on the bone regeneration process. In vitro experiments using different cells (e.g. SaOs2, hMSCs, and osteoblast-like cells) have revealed that CaP coatings enhance cellular adhesion, proliferation, and differentiation to promote bone regeneration. However, in vivo, the exact mechanism of osteogenesis in response to CaP coatings is unclear, indeed there are conflicting reports of the effectiveness of CaP coatings with results ranging from highly effective to no significant or even negative effects. This review will therefore highlight progress in CaP coatings for orthopaedic implants and discuss the future research and use of these devices. Currently, an exciting area of research is in bioactive hybrid composite CaP-based coatings containing both inorganic (CaP coating) and organic (collagen, BMPs, RGD etc.) components with the aim of promoting tissue ingrowth and vascularisation. Further investigations are necessary to reveal the relative influences of implant design, surgical procedure, and coating characteristics (thickness, structure, topography, porosity, wettability etc) on the long-term clinical effects of hybrid CaP coatings. In addition to commercially available plasma spraying, other effective routes for the fabrication of hybrid CaP coatings for clinical use still need to be determined and current progress is discussed.
Due to its excellent bioactivity, 45S5 Bioglass® is being highly considered in tissue engineering scaffold development. In order to enhance vascularization promoting tissue growth, these scaffolds typically have a highly interconnected porous structure with a porosity between 80 and >90%. Often, Bioglass®-based scaffolds of such a high porosity have insufficient stiffness. In order to increase the stiffness of Bioglass®-based scaffolds fabricated by the foam replica method, the herein investigated scaffolds were coated with a number of different biopolymers, including: collagen, gelatin, polycaprolactone (PCL), alginate and poly(l-lactic acid). The resulting stiffness gain was quantified by means of ultrasonic measurements. Accordingly, PCL and collagen coatings increased the scaffold stiffness, as compared to uncoated scaffolds, by 58 and 38%, respectively; while no remarkable stiffness increase was recorded for the other coatings. Additionally, scanning electron microscopy images of polymer coated scaffolds revealed that PCL coatings had not clogged the scaffold's micropores, which is deemed essential for cell seeding and to enable in-growth of bone tissue. Thus, the application of PCL coatings represents a promising strategy for mechanical competence enhancement of Bioglass®-based scaffolds for bone tissue engineering.
Magnesium alloys are potential biodegradable materials and have received increasing attention due to their outstanding biological performance and mechanical properties. However, rapid degradation in the physiological environment and potential toxicity limit clinical applications. Recently, special magnesium-calcium (Mg-Ca) and magnesium-strontium (Mg-Sr) alloys with biocompatible chemical compositions have been reported but the rapid degradation still does not meet clinical requirements. In order to improve the corrosion resistance, a rough, hydrophobic, and ZrO2-containing surface film is fabricated on Mg-Ca and Mg-Sr alloy by dual zirconium and oxygen ion implantation. Weight loss measurements and electrochemical corrosion tests show that the corrosion rate of the Mg-Ca and Mg-Sr alloys is reduced appreciably after surface treatment. A systematic investigation of the in vitro cellular response and antibacterial capability of the modified binary magnesium alloys is performed. The amounts of adherent bacteria on the Zr-O implanted and Zr-implanted samples diminish remarkably compared to the un-implanted control. In addition, significantly enhanced cell adhesion and proliferation are observed from the Zr-O implanted sample. The results suggest that dual zirconium and oxygen ion implantation, which effectively enhances the corrosion resistance, in vitro biocompatibility, and antimicrobial properties of Mg-Ca and Mg-Sr alloys, provides a simple and practical means to expedite clinical acceptance of biodegradable magnesium alloys.
Chitosan-polycaprolactone (CH-PCL) copolymers with various PCL percentages less than 45wt% were synthesized. Different CH-PCLs were respectively blended with Type-II collagen at prescribed ratios to fabricate a type of layered porous scaffolds with some biomimetic features while using sodium tripolyphosphate as a crosslinker. The compositions of different layers inside scaffolds were designed in a way so that from the top layer to the bottom layer collagen content changed in a degressive trend contrary to that of chitosan. A combinatorial processing technique involving adjustable temperature gradients, collimated photothermal heating and freeze-drying was used to construct desired microstructures of scaffolds. The resultant scaffolds had highly interconnected porous layers with a layer thickness of around 1mm and porous interface zones without visual clefts. Results obtained from SEM observations and measurements of pore parameters and swelling properties as well as mechanical examinations confirmed that graded average pore-size and porosity, gradient swelling index and oriented compressive modulus for certain scaffolds were synchronously achieved. In addition, certain evaluations of cell-scaffold constructs indicated that the achieved scaffolds were able to well support the growth of seeded chondrocytes. The optimized collagen/CH-PCL scaffolds are partially similar to articular cartilage extracellular matrix in composition, porous microarchitecture, water content and compressive mechanical properties, suggesting that they have promising potential for applications in articular cartilage repair.
In this study the α″ stress-induced martensitic transformation and damping behaviour of the superelastic β-Ti–25Ta–25Nb alloy are investigated by tensile tests at room temperature and by dynamic mechanical analysis (DMA) in tensile mode for different applied stresses. Tensile tests show a fully non-linear elastic domain and, consequently, a specific method is proposed to determine the elastic modulus. Due to the wide range of temperature over which the martensitic transformation occurs in this class of alloys, the martensitic start temperature, Ms, is not a relevant parameter to characterize the transformation and the temperature Mmax corresponding to the temperature of maximum transformation is used. The important gap between these two temperatures explains the fully non-linear elastic behaviour of this alloy during conventional tensile tests. It is observed that two main damping sources occur in this alloy: friction at austenite/martensite interfaces during the martensitic transformation and friction at martensite/martensite interfaces at lower temperature. However, a third unexpected damping peak is also observed at high stress. Its origin is discussed with respect to the orientation of the applied stress and with regard to the most favourably oriented martensite variants determined by Schmid factor analysis.
A mesoporous hydroxyapatite (HA) coating was prepared on a β-tricalcium phosphate (β-TCP) porous scaffold by a sol-gel dip-coating method using the block copolymer Pluronic F127 (EO106PO70EO106) as the template. For application as a bone graft, in vitro cell response and bone-related protein expression of mesoporous HA coated β-TCP scaffold were investigated, using the non-mesoporous HA coated scaffold as the control group, to evaluate the influence of the mesoporous structure on the biological properties of HA coating. It was found that the increased surface area of the mesoporous HA coating greatly affected the response of MC3T3-E1 osteoblasts and the expression of proteins. An enzyme-linked immunosorbent assay recorded a significantly higher expression of alkaline phosphatase (ALP) and bone sialoprotein (BSP) in the mesoporous group than those in the control group (*p<0.05) after different incubation periods. The introduction of mesopores enhanced the expression of ALP and BSP in the cells grown on the mesoporous HA coatings, on the premise of maintaining the protein expression in a sequence to ensure the correct temporo-spatial expression in osteogenesis. These results indicated that the mesoporous HA coating would provide a good environment for cell growth, suggesting that it could be used as the coating material for the surface modification of the tissue engineering scaffolds.
There is an increasing interest in the development of magnesium alloys both for industrial and biomedical applications. Industrial interest in magnesium alloys is based on strong demand of weight reduction of transportation vehicles for better fuel efficiency, so higher strength, and better ductility and corrosion resistance are required. Nevertheless, biomedical magnesium alloys require appropriate mechanical properties, suitable degradation rate in physiological environment, and what is most important, biosafety to human body. Rather than simply apply commercial magnesium alloys to biomedical field, new alloys should be designed from the point of view of nutriology and toxicology. This article provides a review of state-of-the-art of magnesium alloy implants and devices for orthopedic, cardiovascular and tissue engineering applications. Advances in new alloy design, novel structure design and surface modification are overviewed. The factors that influence the corrosion behavior of magnesium alloys are discussed and the strategy in the future development of biomedical magnesium alloys is proposed.
Porous magnesium-based materials are biodegradable and promising for use in orthopaedic applications, but their applications are hampered by their difficult fabrication. This work reports the preparation of porous magnesium materials by a powder metallurgy technique using ammonium bicarbonate as spacer particles. The porosity of the materials depended on the amount of ammonium bicarbonate and was found to have strong negative effects on flexural strength and corrosion behaviour. However, the flexural strength of materials with porosities of up to 28 vol.% was higher than the flexural strength of non-metallic biomaterials and comparable with that of natural bone.
Mg–3Nd–0.2Zn–0.4Zr alloy with good mechanical properties is a new type of biodegradable magnesium alloy. In order to improve the surface stability in the initial healing stage and foster tissue growth on biomedical implants made of this Mg alloy, oxygen plasma immersion ion implantation (O-PIII) is conducted to modify the alloy surface. Although O-PIII increases the thickness of the surface oxide, no significant improvement in the surface corrosion resistance is observed. Hence, surface alloying with Al and Cr by means of high-energy ion implantation is conducted prior to O-PIII. The electrochemical data obtained in simulated body fluids, including polarization curves and electrochemical impedance spectra (EIS), reveal that the surface corrosion resistance is improved after surface alloying. Our results show that surface alloying with Cr produces the best result in this study. The improvement stems from the formation of Al or Cr-containing oxide films in the implanted layer.
Helium irradiation of metals has long been studied in efforts to understand the damaging aspects associated with applications in fusion reactors and tritium storage. This work examines the possibility of using low energy helium ion bombardment as a method of producing a beneficial surface texturization to promote bone growth on orthopedic implants. Using 300 eV helium ions, two unique porous titanium surfaces were created when substrates were held at temperatures of roughly 450 °C and 600 °C. The surfaces were physically characterized by scanning electron microscopy (SEM) and scanning white light interferometry. A week long hFOB 1.19 cell culture was performed using an untreated titanium control to evaluate the suitability of these surfaces for orthopedic implants. Cell health and viability were evaluated by calcein AM live cell staining, MTT assay, and SEM. The results show that helium texturizations promote cellular activity and have no detrimental effect on cell health.
The properties of thin calcium-phosphate coatings formed by radio-frequency magnetron sputtering of a solid target made from hydroxyapatite on the surface of the thermoplastic copolymer of vinilidene fluoride and tetrafluoroethylene (VDF–TeFE) were investigated. Atomic force microscopy energy dispersive analysis and optical goniometry showed that deposited calcium-phosphate coatings change significantly the morphological, electrical, chemical, and contact properties of the surface of the initial polymeric substrates. These modified surfaces widen the scope of medical application of the thermoplastic copolymer.
It is important to improve the compatibility of hydroxyapatite (HA) nanoparticles in biodegradable polyesters to obtain desirable nanocomposites for bone tissue engineering applications. Polymer grafting has been proven an efficient way to get nanohybrids with good dispersibility in polymeric matrixes. In this paper, a new strategy to prepare HA–poly(l-lactide) (PLLA) nanohybrids was developed, where PLLA oligomers were grafted from HA nanoparticle surfaces via surface-initiated atom transfer radical polymerization (ATRP) of methylacrylate group terminated PLLA macromonomers (PLLA-MA). HA with the derived ATRP initiators was obtained by (1) preparation of HA from precursors in the presence of 3-aminopropyl-triethoxysilane (APTS) to produce the HA surface with terminal NH2 groups (HA–NH2) and (2) reaction of the NH2 groups of the HA–NH2 nanoparticles with 2-bromoisobutyryl bromide (BIBB) to produce the 2-bromoisobutyryl-immobilized nanoparticles (HA–Br). The obtained HA–PLLA nanohybrids demonstrated good dispersibility in chloroform. With the good dispersion of HA–PLLA nanohybrids in PLLA matrix, the resultant PLLA/HA–PLLA nanocomposites could much faster induce bone-like apatite-formation in simulated body fluids (SBF) than the PLLA/HA counterparts where the HA nanoparticles aggregated heavily. With the versatility of ATRP, properly, grafting oligomeric PLLA chains from HA nanoparticle surfaces is an effective means for the design of novel HA–polymer biohybrids for future bone tissue engineering applications.
Cu/Ti films of various Cu/Ti ratios were prepared on a TiNi alloy via vacuum arc plasma deposition. The phase composition, structure, and concentration of elements were investigated via X-ray diffraction and X-photoelectron energy spectrum. The hemolysis ratio and platelet adhesion of the different films were characterized to evaluate blood compatibility. The corrosion and ion release behavior were investigated via a typical immersion test and electrochemical method. The growth of endothelial cells (ECs) was investigated, and methylthiazolyte-trazolium method was employed to evaluate the effect of Cu2+. The sophisticated films showed good compatibility. However, with increasing quality ratio of Cu/Ti, the hemolysis ratio increased, and some platelets started to break slightly. The Cu2+ release was gradually stabilized. The open circuit potential of the Cu/Ti film-modified samples was lower than that of the TiNi substrate. The polarization test result indicates that the passivation stability performance of Cu/Ti film samples is less than the TiNi substrate, and is favorable to Cu2+ release. The adhesion and proliferation of ECs would be inhibited with 10 wt.% Cu concentration of the film, and ECs would undergo apoptosis at >50 wt.% concentration. A Cu/Ti film with good compatibility and anti-endothelialization has potential applications for special cardiovascular devices.
To improve the corrosion resistance of biomedical nickel titanium (NiTi) alloy, a polymeric allylamine film is deposited by plasma polymerization. The chemical composition, surface morphology, and thickness of the polymer film are investigated with X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and scanning electron microscopy (SEM). The corrosion behavior of the coated NiTi and bare NiTi samples is compared by polarization test and electrochemical impedance spectroscopy (EIS) in simulated body fluid. The results show that the polymeric film lowers the corrosion current density and increases the polarization resistance, indicating improved corrosion resistance. The plasma polymerized coating is expected to reduce corrosion risks of biomedical NiTi alloy in clinical use.
A newly developed magnesium implant is used to stimulate bone formation in vivo. The magnesium implant after undergoing dual aluminum and oxygen plasma implantation is able to suppress rapid corrosion, leaching of magnesium ions, as well as hydrogen gas release from the biodegradable alloy in simulated body fluid (SBF). No released aluminum is detected from the SBF extract and enhanced corrosion resistance properties are confirmed by electrochemical tests. In vitro studies reveal enhanced growth of GFP mouse osteoblasts on the aluminum oxide coated sample, but not on the untreated sample. In addition to that a small amount (50 ppm) of magnesium ions can enhance osteogenic differentiation as reported previously, our present data show a low concentration of hydrogen can give rise to the same effect. To compare the bone volume change between the plasma-treated magnesium implant and untreated control, micro-computed tomography is performed and the plasma-treated implant is found to induce significant new bone formation adjacent to the implant from day 1 until the end of the animal study. On the contrary, bone loss is observed during the first week post-operation from the untreated magnesium sample. Owing to the protection offered by the Al2O3 layer, the plasma-treated implant degrades more slowly and the small amount of released magnesium ions stimulate new bone formation locally as revealed by histological analyses. Scanning electron microscopy discloses that the Al2O3 layer at the bone-implant interface is still present two months after implantation. In addition, no inflammation or tissue necrosis is observed from both treated and untreated implants. These promising results suggest that the plasma-treated magnesium implant can stimulate bone formation in vivo in a minimal invasive way and without causing post-operative complications.
Porous poly(ε-caprolactone) (PCL) scaffolds are widely used as in vivo implants in tissue engineering, and their long-term degradation behaviors are of great importance for their in vivo performances. However, the influence of porosity on long-term degradation of PCL scaffold in phosphate buffer solution (PBS) has been rarely reported so far. Herein, a 72-week degradation study of PCL scaffolds with various porosities was conducted to elucidate the changes of physico-chemical properties such as weight, molecular weight, morphology and compressive modulus. Within 72 weeks, PCL scaffolds experienced three stages: stable stage, mechanical loss stage and structural collapse stage. The higher porosity induced the severer loss of weight, molecular weight and compressive modulus. It was found that a minimal acid autocatalysis also happened in the scaffold samples with low porosities (less than 85%). Cellular response on the scaffolds with various porosities was further evaluated. The cell ingrowth improved on the scaffold with high porosity (e.g. S-10) in contrast to those with low porosity (e.g. S-6 and S-4). The combined results demonstrated that an optimal porosity of PCL scaffolds should be designed greater than 90% due to the appropriate degradation rate and good cell performance.
Rapid degradation is the major obstacle hindering a wider use of magnesium based biomaterials. In this work, silicon, one of the essential elements in the bone tissues, is implanted into WE43 magnesium alloy to improve its corrosion behavior. X-ray photoelectron spectroscopy (XPS) reveals the formation of a gradient surface structure with a gradual transition from a Si-rich oxide layer to Si-rich layer. Electrochemical studies reveal that Si implantation offers a remarkable improvement in the corrosion resistance of WE43 Mg alloy in simulated body fluid (SBF).
Much effort has been dedicated to developing scaffolds that can mimic native microenvironments to promote tissue regeneration. A natural tissue scaffold provides not only a three-dimensional (3-D) structural support but also nanotextured surfaces comprising of a fibrous network for cell adhesion and signaling. In addition to its function as a structural template, the scaffold also increases cell–cell and cell–matrix interactions, which in turn directs cell proliferation and differentiation. Microfabrication techniques can create 3-D scaffolds with microporous structures, which are important to cell infiltration and nutrients transport. Nanofabrication techniques can be used to create surfaces with desirable chemistry and nanotopography, which has led to remarkable findings on how surfaces, through their nanoscale features, affect cellular behaviors. Tissue regeneration requires 3-D scaffolds with both microporous structures and nanotextured surfaces. However, scaffolds created by microfabrication usually lack a nanotextured surface, while nanotextured scaffolds generated from nanofabrication lack a 3-D microenvironment. Recent research in tissue engineering has paid great attention to combining these two scaffold features and developing novel methods for their fabrication. In this review paper, we first give a brief introduction on the influence of 3-D microstructures and nanotopographies on cellular functions, including cell adhesion, proliferation, morphogenesis and differentiation. Recent development of fabrication methods to produce 3-D fibrous scaffolds with microporous structures and nanotextures is then discussed with some examples of their applications.
The CaO–MxOy–SiO2–P2O5 (M = Zr, Mg, Sr) MBG scaffolds have been successfully prepared by the combination of polyurethane sponge and block copolymerEO20PO70EO20 (P123) as co-templates and evaporation-induced self-assembly (EISA) process using Ca, P, Si and M sources. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and N2 adsorption–desorption technique were used to analyze the microstructure, pore size and morphology of these MBG scaffolds. These MBG scaffolds have the interconnected macroporous network with the pore diameter of 200–400 μm and the mesoporous wall with the mesopore size of 3–4 nm. The effects of the partial substitution of ZrO2, MgO or SrO for CaO on the physiochemical and biological properties of the MBG scaffolds were evaluated by the mechanical strength, ion dissolution, apatite-forming ability, and proliferation, alkaline phosphatase (ALP) activity and osteogenic expression of osteoblast-like cellsMC3T3-E1. The results showed that the ZrO2-substituted MBG scaffold enhanced the mechanical strength, and exhibited a slower ion dissolution rate and more significant potential to stabilize the pH environment compared to other MBG scaffolds. The CaO–MxOy–SiO2–P2O5 MBG scaffolds showed a good apatite-forming ability and facilitated osteoblastcells' proliferation and differentiation to different extents. In particular, the ZrO2-substituted MBG scaffold exhibited the best biological property compared to other MBG scaffolds. Furthermore, the CaO–MxOy–SiO2–P2O5 MBG scaffolds also had a sustained drug release property for use in local drug delivery therapy. Therefore, the CaO–MxOy–SiO2–P2O5 MBG scaffolds have more potential for the application in bone tissue regeneration.
The aim of this study was to demonstrate the feasibility of using a steam autoclave process for sterilization and simultaneously thermal-crosslinking of lyophilized chitosan scaffolds. This process is of great interest in biomaterial development due to its simplicity and low toxicity. The steam autoclave process had no significant effect on the average pore diameter (~70μm) and overall porosity (>80%) of the resultant chitosan scaffolds, while the sterilized scaffolds possessed more homogenous pore size distribution. The sterilized chitosan scaffolds exhibited an enhanced compressive modulus (109.8kPa) and comparable equilibrium swelling ratio (23.3). The resultant chitosan scaffolds could be used directly for in vitro cell culture without extra sterilization. The data of in vitro studies demonstrated that the scaffolds facilitated cell attachment and proliferation, indicating great potential for soft tissue engineering applications.
Highly porous 45S5 Bioglass®-based scaffolds fabricated by a foam replication technique were coated with electrically conductive organic-inorganic hybrid layers containing graphene by a solution method. α,ω-Triethoxysilane terminated poly (ethylene glycol) and tetraethoxysilane were used as the precursors of the organic-inorganic hybrid coatings, that contained 1.5wt.% of homogeneously dispersed graphene nanoplatelets. The resulting coated scaffolds retained their original high porosity and interconnected pore structure after coating. The presence of graphene did not impair the bioactivity of the scaffolds in simulated body fluid. Initial tests carried out using MG-63 cells demonstrated that both uncoated scaffolds and scaffolds coated with organic/inorganic hybrids containing graphene offered the cultured cells an adequate surface for cell attachment, spreading and expression of extracellular matrix. The results showed that scaffolds coated with graphene are biocompatible and they can support cellular activity. The electrical conductivity introduced by the coating might have the potential to increase tissue growth when cell culture is carried out under an applied electric field.
We present a method of preparing and characterizing nanostructured bioactive motifs using a combination of nanoimprint lithography and surface functionalization. Nanodots were fabricated on silicon surfaces and modified with a cell-adhesive RGD peptide for studies in human mesenchymal stem cell adhesion and differentiation. We report that bioactive nanostructures induce mature focal adhesions on human mesenchymal stem cells with an impact on their behavior and dynamics specifically in terms of cell spreading, cell-material contact, and cell differentiation.
Scaffolds fabricated by current methods often lack the combination of high strength and high porosity for skeletal substitution of load-bearing bones. In this work, freeze extrusion fabrication (FEF), a solid freeform fabrication technique, was investigated for the creation of porous and strong bioactive glass (13–93) scaffolds for potential applications in the repair of loaded bone. The process parameters for forming three-dimensional (3D) scaffolds with a pre-designed, grid-like microstructure by FEF were determined. Following thermal treatment of the as-formed constructs at temperatures up to 700°C, scaffolds consisting of dense glass struts and interconnecting pores (porosity≈50%; pore width≈300μm) were obtained. These scaffolds showed an elastic mechanical response in compression, with a compressive strength of 140±70MPa and an elastic modulus of 5.5±0.5GPa, comparable to the values for human cortical bone. The scaffolds supported the proliferation of osteogenic cells in vitro, showing their biocompatibility. These results indicate that 13–93 bioactive glass scaffolds created by the FEF method could have potential application in the repair and regeneration of load-bearing bones.
Medium chain length polyhydroxyalkanoates, mcl-PHAs (C6–C14 carbon atoms), are polyesters of hydroxyalkanoates produced mainly by fluorescent Pseudomonads under unbalanced growth conditions. These mcl-PHAs which can be produced using renewable resources are biocompatible, biodegradable and thermoprocessable. They have low crystallinity, low glass transition temperature, low tensile strength and high elongation to break, making them elastomeric polymers. Mcl-PHAs and their copolymers are suitable for a range of biomedical applications where flexible biomaterials are required, such as heart valves and other cardiovascular applications as well as matrices for controlled drug delivery. Mcl-PHAs are more structurally diverse than short chain length PHAs and hence can be more readily tailored for specific applications. Composites have also been fabricated using mcl-PHAs and their copolymers, such as poly (3-hydroxyoctanoate) [P(3HO)] combined with single walled carbon nanotubes and poly(3-hydroxbutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HHx)] combined with hydroxyapatite. Because of these attractive properties of biodegradability, biocompatibility and tailorability, Mcl-PHAs and their composites are being increasingly used for biomedical applications. However, studies remain limited mainly to P(3HO) and the copolymer P(3HB-co-3HHx), which are the only mcl-PHAs available in large quantities. In this review we have consolidated current knowledge on the properties and biomedical applications of these elastomeric mcl-PHAs, their copolymers and their composites.
In order to enhance the surface wear resistance and nitrogen diffusion during plasma treatment, orthopedic NiTi alloy is subjected to surface mechanical attrition treatment (SMAT) and a nanocrystalline and partial amorphous structure is fabricated in the surface layer. It is found that hardness in the surface layer is notably improved. The corrosion behavior is systematically studied in a 0.9% NaCl physiological solution by electrochemical methods. Potentiodynamic polarization measurements indicate that the corrosion resistance of SMAT NiTi with the surface nanocrystalline and partial amorphous structure is significantly enhanced compared to the bare NiTi with coarse grains. Both corrosion potential (Ecorr) measurements and electrochemical impedance spectroscopy (EIS) reveal that a passive oxide layer is readily formed on the SMAT NiTi during early immersion in the 0.9% NaCl solution. When the passive oxide layer has stabilized after long exposure in the 0.9% NaCl solution, corrosion induced by Cl− begins to degrade the passive oxide film. The observed corrosion behavior of SMAT NiTi is considered to be associated with the surface nanocrystalline and amorphous structure.