Materials For Tissue Repair Research Articles

MXene-Reinforced Composite Cryogel Scaffold for Neural Tissue Repair

The development of effective materials for neural tissue repair remains a major challenge in regenerative medicine. In this study, we present a novel MXene-reinforced composite cryogel scaffold designed for neural tissue regeneration. MXenes, a class of two-dimensional materials with high conductivity and biocompatibility, were integrated into a polyvinyl alcohol (PVA) matrix via cryopolymerization to form a macroporous, mechanically stable scaffold. The morphology, mechanical properties, and swelling behavior of the cryogel with different MXene contents have been assessed. The effects of MXene on the viability/proliferation and differentiation of neural cells (PC-12) cultured in the composite cryogel were elucidated. The MXene/PVA cryogel demonstrated excellent cell-supporting potential, with MXene not only showing no toxicity but also promoting the proliferation of cultured PC-12. Additionally, MXene induced a neuritogenesis-like process in the cells as evidenced by morphological changes and the enhanced expression of the neural marker β-III-tubulin. The neuroprotective properties of the MXene component were revealed by the alleviation of oxidative stress and reduction of intracellular ROS levels. These findings highlight the potential of MXene-embedded PVA cryogel as a promising material that can be further used in conjunction with electrostimulation therapy for advancing strategies in neural tissue engineering.

A super soft thermoplastic biodegradable elastomer with high elasticity for arterial regeneration

Elastomers with innovative performance will provide new opportunities for solving problems in soft tissue repair, such as arterial regeneration. Herein, we present a thermoplastic biodegradable elastomer (PPS) that differs from the rigid, low-elastic traditional ones. It shows super softness (0.41 ± 0.052 MPa), high stretchability (3239 ± 357 %), and viscoelasticity similar to natural soft tissues. In addition, it also has good processability and appropriate degradability, estimated at 4–8 months for complete degradation in vivo. This excellent overall performance makes it a great support material for soft tissue repair and a powerful modifying agent for improving existing materials. For example, introducing it into poly(l-lactide) scaffolds through thermally induced phase separation can create a unique microporous structure with interconnected large pores (diameter >10 μm), demonstrating high efficiency in inducing cell infiltration. Blending it with poly(ε-caprolactone) through electrospinning can produce a composite fibrous film with significantly improved comprehensive performance, displaying artery-matched mechanical properties. Building on the above, we constructed a tri-layer tissue-engineered vascular graft for arterial regeneration, exhibiting promising remodeling outcomes in rabbits.

Biomimetic tubular materials: from native tissues to a unifying view of new vascular, tracheal, gastrointestinal, oesophageal, and urinary grafts.

Repairing tubular tissues-the trachea, the esophagus, urinary and gastrointestinal tracts, and the circulatory system-from trauma or severe pathologies that require resection, calls for new, more effective graft materials. Currently, the relatively narrow family of materials available for these applications relies on synthetic polymers that fail to reproduce the biological and physical cues found in native tissues. Mimicking the structure and the composition of native tubular tissues to elaborate functional grafts is expected to outperform the materials currently in use, but remains one of the most challenging goals in the field of biomaterials. Despite their apparent diversity, tubular tissues share extensive compositional and structural features. Here, we assess the current state of the art through a dual layer model, reducing each tissue to an inner epithelial layer and an outer muscular layer. Based on this model, we examine the current strategies developed to mimic each layer and we underline how each fabrication method stands in providing a biomimetic material for future clinical translation. The analysis provided here, addressed to materials chemists, biomaterials engineers and clinical staff alike, sets new guidelines to foster the elaboration of new biomimetic materials for effective tubular tissue repair.

Application of Fetal Membranes and Natural Materials for Wound and Tissue Repair.

The human fetal membrane is a globally accepted biological biomaterial for wound and tissue repair and regeneration in numerous fields, including dermatology, ophthalmology, and more recently orthopedics, maxillofacial and oral surgery, and nerve regeneration. Both cells and matrix components of amnion and chorion are beneficial, releasing a diverse range of growth factors, cytokines, peptides, and soluble extracellular matrix components. Beside fetal membranes, numerous natural materials have also been reported to promote wound healing. The biological properties of these materials may potentiate the pro-healing action of fetal membranes. Comparison of such materials with fetal membranes has been scant, and their combined use with fetal membranes has been underexplored. This review presents an up-to-date overview of (i) clinical applications of human fetal membranes in wound healing and tissue regeneration; (ii) studies comparing human fetal membranes with natural materials for promoting wound healing; and (iii) the literature on the combined use of fetal membranes and natural pro-healing materials.

Comprehensive characterization of natural polysaccharide-based hydrogels with gradient structure in concentration and stiffness

Gradient hydrogels are functionally graded biomaterials that over the last decades have garnered significant attention as valuable materials for tissue repair and regeneration. This study elucidates key factors crucially determining the character or pattern of a buoyancy-driven gradient in agarose hydrogels and also provides fundamental information regarding the complex interpretation of the formed gradient hydrogels obtained by the different characterization techniques, including rheology, UV-Vis spectroscopy, FCS, AFM, SEM. The employed techniques were successfully optimized to enhance the understanding of the gradient properties of these hydrogels. Demonstrated results showed that the agarose concentration gradient could be successfully controlled and tailored, which offers a valuable contribution to the design of gradient hydrogel. Moreover, a novel method for determining the average agarose concentration along the gradient axis is presented, improving the precision of gradient characterization. The integration of these approaches significantly enhances the comprehension of the internal structure and properties of gradient materials, contributing to advancements in their understanding and application.

Construction of living-cell tissue engineered amniotic membrane for ocular surface disease

BackgroundHuman amniotic membrane (AM) transplantation has been applied to treat ocular surface diseases, including corneal trauma. The focus of much deliberation is to balance the mechanical strength of the amniotic membrane, its resistance to biodegradation, and its therapeutic efficacy. It is commonly observed that the crosslinked human decellularized amniotic membranes lose the functional human amniotic epithelial cells (hAECs), which play a key role in curing the injured tissues.Methods and resultsIn this study, we crosslinked human decellularized amniotic membranes (dAM) with genipin and re-planted the hAECs onto the genipin crosslinked AM. The properties of the AM were evaluated based on optical clarity, biodegradation, cytotoxicity, and ultrastructure. The crosslinked AM maintained its transparency. The color of crosslinked AM deepened with increasing concentrations of genipin. And the extracts from low concentrations of genipin crosslinked AM had no toxic effect on human corneal epithelial cells (HCECs), while high concentrations of genipin exhibited cytotoxicity. The microscopic observation and H&E staining revealed that 2 mg/mL genipin-crosslinked dAM (2 mg/mL cl-dAM) was more favorable for the attachment, migration, and proliferation of hAECs. Moreover, the results of the CCK-8 assay and the transwell assay further indicated that the living hAECs’ tissue-engineered amniotic membranes could facilitate the proliferation and migration of human corneal stromal cells (HCSCs) in vitro.ConclusionsIn conclusion, the cl-dAM with living hAECs demonstrates superior biostability and holds significant promise as a material for ocular surface tissue repair in clinical applications.

Designing polysaccharide materials for tissue repair and regeneration

Designing polysaccharide materials for tissue repair and regeneration

Bioactive Materials That Promote the Homing of Endogenous Mesenchymal Stem Cells to Improve Wound Healing.

Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.

Smart responsive staple for dynamic promotion of anastomotic stoma healing

The precise combination of conflicting biological properties through sophisticated structural and functional design to meet all the requirements of anastomotic healing is of great demand but remains challenging. Here, we develop a smart responsive anastomotic staple (Ti–OH-MC) by integrating porous titanium anastomotic staple with multifunctional polytannic acid/tannic acid coating. This design achieves dynamic sequential regulation of antibacterial, anti-inflammatory, and cell proliferation properties. During the inflammatory phase of the anastomotic stoma, our Ti–OH-MC can release tannic acid to provide antibacterial and anti-inflammatory properties, together with immune microenvironment regulation function. At the same time, as the healing progresses, the multifunctional coating gradually falls off to expose the porous structure of the titanium anastomotic staple, which promotes cell adhesion and proliferation during the later proliferative and remodeling phases. As a result, our Ti–OH-MC exceeds the properties of clinically used titanium anastomotic staple, and can effectively promote the healing. The staple’s preparation strategy is simple and biocompatible, promising for industrialisation and clinical application. This work provides an effective anastomotic staple for anastomotic stoma healing and serve as a reference for the functional design and preparation of other types of titanium-based tissue repair materials.

An injectable bone paste of poly (lactic acid)/zinc-doped nano hydroxyapatite composite microspheres for skull repair

In this study, poly (lactic acid)/zinc-doped nano hydroxyapatite (PLA/nano-ZnHA) composite microspheres were prepared and formed into injectable bone paste with sodium alginate (SA) and polyvinyl alcohol (PVA) for bone defect repair. The effect of component of bone paste on injectability and zinc doping content related biological properties were mainly discussed. An injectable bone paste of PLA/nano-ZnHA composite microspheres (CM) was formed in mass ratio of (2.5–25):(0.25–4): (0–2.5):(20−65) of CM, SA, PVA and water with the favorable injectability (average force:4.46±1.72 N). In vitro 5%-10% zinc doping content displayed significantly higher promotion on cell proliferation and osteogenic differentiation than 15%-20% zinc doping content. Furthermore, in vivo the significant promoting effect of 0–5% zinc doping in ZnHA on bone repair was observed. Although 5% zinc doping content did not show a significant enhancement in bone volume/tissue volume (BV/TV), it has the ability to improve the bone mineral density (BMD) in early stage of bone repair compared with the 0% zinc doping content. The PLA/nano-ZnHA composite microsphere injectable paste with convenient surgical operation and well filling ability has the potential to become a competitive tissue repair material.

Effect of Silver Content and T4 Treatment on the In Vitro Degradation Behavior of Gasar Porous Mg–Ag Alloy

Mg–Ag alloy has potential as a material for bone tissue repair, but the faster degradation rate in vivo limits its use in medical applications. In this study, pure Mg and Mg99.5Ag0.5 alloy with a porous structure are prepared using the metal/gas eutectic unidirectional solidification method (Gasar process). The influence of introducing Ag on the degradation behavior of porous Mg99.5Ag0.5 and pure Mg is investigated. The addition of Ag increases the compressive strength and elastic modulus of the material. The corrosion resistance of as‐cast Mg99.5Ag0.5 alloy decreases due to localized aggregation of Ag in the alloys. Therefore, the T4 (solution treatment) is chosen for the Mg99.5Ag0.5 alloy. After T4 treatment, due to the uniform distribution of Ag atoms in the alloy, the corrosion behavior on the alloy surface is more uniform, and a denser Mg(OH)2 passivation layer is formed on the surface, which reduces the degradation rate of Mg99.5Ag0.5. Importantly, insoluble Ca–P compounds in the form of hydroxyapatite (HA) phases gradually grown on passivated layers of porous T4 Mg99.5Ag0.5 contribute to bone growth. This indicates the feasibility of using the T4 Gasar porous Mg99.5Ag0.5 alloy as a potential tissue engineering scaffold.

Electroactive Biomaterials Regulate the Electrophysiological Microenvironment to Promote Bone and Cartilage Tissue Regeneration

AbstractThe incidence of large bone and articular cartilage defects caused by traumatic injury is increasing worldwide; the tissue regeneration process for these injuries is lengthy due to limited self‐healing ability. Endogenous bioelectrical phenomenon has been well recognized to play an important role in bone and cartilage homeostasis and regeneration. Studies have reported that electrical stimulation (ES) can effectively regulate various biological processes and holds promise as an external intervention to enhance the synthesis of the extracellular matrix, thereby accelerating the process of bone and cartilage regeneration. Hence, electroactive biomaterials have been considered a biomimetic approach to ensure functional recovery by integrating various physiological signals, including electrical, biochemical, and mechanical signals. This review will discuss the role of endogenous bioelectricity in bone and cartilage tissue, as well as the effects of ES on cellular behaviors. Then, recent advances in electroactive materials and their applications in bone and cartilage tissue regeneration are systematically overviewed, with a focus on their advantages and disadvantages as tissue repair materials and performances in the modulation of cell fate. Finally, the significance of mimicking the electrophysiological microenvironment of target tissue is emphasized and future development challenges of electroactive biomaterials for bone and cartilage repair strategies are proposed.

Development of triple-functionalized calcium phosphate nanoparticles as an advanced drug delivery system for bone tissue repair

IntroductionDuring tissue repair or regeneration, several bioactive molecules are released and interact with each other and act as complex additives or inhibitors for tissue reconstruction. In this study, the bone-healing effects of the combination treatment with tumor necrosis factor-α (TNF-α) inhibition, vascular endothelial growth factor A (VEGF-A) and bone morphogenetic protein-7 (BMP-7) release by gene silencing, and gene transfection with calcium phosphate nanoparticles (CaP) in the rat femoral head was histologically, morphologically, and biochemically evaluated. MethodsA triple-functionalized paste of CaP carrying plasmid DNA encoding for BMP-7 and for VEGF), and siRNA against TNF-α was developed and denoted as CaP3mix. To compare the effects of 3mixCaP, CaP with plasmid DNA encoding BMP-7, VEGF, or siRNA encoding TNF-α was prepared and denoted as CaP/PEI/pBMP-7/SiO2, CaP/PEI/pVEGF/SiO2, or CaP/PEI/siRNA-TNF-α/SiO2, respectively. The bone healing in bone defects in the rat femoral head was investigated after 10 and 21 days of implantation. ResultsThe levels of bone formation-related markers OCN, Runx2, and SP7 increased at the protein and gene levels in 3mixCaP after 10 days, and 3mixCaP significantly accelerated bone healing compared with the other treatments after 21 days of implantation. ConclusionThe triple-functionalized CaP paste loading plasmid DNA encoding BMP-7 and VEGF and siRNA encoding TNF-α is a promising bioactive material for bone tissue repair.

Drug Loaded 3D-Printed Poly(ε-Caprolactone) Scaffolds for Local Antibacterial or Anti-Inflammatory Treatment in Bone Regeneration.

Annual bone grafting surgeries due to bone fractures, resections of affected bones, skeletal anomalies, osteoporosis, etc. exceed two million worldwide. In this regard, the creation of new materials for bone tissue repair is one of the urgent tasks of modern medicine. Additive manufacturing, or 3D printing, offers great opportunities for the development of materials with diverse properties and designs. In this study, the one-pot technique for the production of 3D scaffolds based on poly(ε-caprolactone) (PCL) loaded with an antibiotic or anti-inflammatory drug was proposed. In contrast to previously described methods to prepare drug-containing scaffolds, drug-loaded PCL scaffolds were prepared by direct 3D printing from a polymer/drug blend. An investigation of the mechanical properties of 3D-printed scaffolds containing 0.5-5 wt% ciprofloxacin (CIP) or dexamethasone (DEX) showed almost no effect of the drug (compression modulus ~70-90 MPa) compared to unfilled PCL (74 MPa). At the same time, introducing the drug and increasing its content in the PCL matrix contributed to a 1.8-6.8-fold decrease in the specific surface area of the scaffold, depending on composition. The release of CIP and DEX in phosphate buffer solution and in the same buffer containing lipase revealed a faster release in enzyme-containing medium within 45 days. Furthermore, drug release was more intensive from scaffolds with a low drug load. Analysis of the release profiles using a number of mathematical dissolution models led to the conclusion that diffusion dominates over other probable factors. In vitro biological evaluation of the scaffolds containing DEX showed moderate toxicity against osteoblast-like and leukemia monocytic cells. Being 3D-printed together with PCL both drugs retain their biological activity. PCL/CIP and PCL/DEX scaffolds demonstrated antibacterial properties against Pseudomonas aeruginosa (a total inhibition after 48 h) and anti-inflammatory activity in experiments on TNFα-activated monocyte cells (a 4-time reduction in CD-54 expression relative to control), respectively.

Tunicate cellulose nanocrystals reinforced modified calcium sulfate bone cement with enhanced mechanical properties for bone repair

Considering the poor mechanical properties of bone cement, its practical application has always been limited. In this study, we introduced tunicate cellulose nanocrystals (TCNCs) into calcium sulfate bone cement for the first time, and multiple enhanced composite bone cement was prepared by the condensation reflux method. Firstly, high-strength modified calcium sulfate hemihydrate (CSH) bone cement was successfully prepared by using tartaric acid, a crystal modifier with a chiral structure. Secondly, the inclusion of TCNCs not only exhibited significant reinforcement and toughening effects but also stimulated the adhesion, proliferation, and differentiation of related osteoblasts. Furthermore, TCNCs encapsulated the CSH particles, overcoming the limitations of excessive degradation rates in bone cement and enabling sustained release of Ca2+, promoting the healing of bone defects. Overall, this study presents novel ideas and methodologies for designing bone cement with exceptional performance. It also provides a new platform for the development of bone tissue engineering and is expected to become a new type of bone regeneration material. The utilization of oceanic resources in this context holds high-value potential, alleviating environmental burdens and providing clinically applicable bone tissue repair materials with broad application prospects.

Microstructure and surface performance of hydroxyapatite-modified multilayer amorphous coating on Ti-rich TiNbZrSn medium entropy alloy: A comparative study

The present study focuses on the formation of a hydroxyapatite-modified amorphous micro-arc oxidized (MAO) coating on the TiNbZrSn medium entropy alloy (TNZS MEA) through micro-arc oxidation and microwave hydrothermal treatment (MHT). The TNZS MEA primarily consists of a body-centered cubic (bcc) and hexagonal closed-packed (hcp) structure, exhibiting a low elastic modulus and high yield strength. A porous coating with an amorphous structure was obtained after MAO treatment, displaying superior corrosion resistance to MAOed Ti. After MHT, the MAOed TNZS MEA exhibited a multilayered structure consisting of three layers: an external growth layer (hydroxyapatite nanorods), an inner layer (amorphous and crystalline structures), and a substrate layer. This composite structure demonstrated enhanced superior apatite-inducing ability and corrosion resistance compared to MHTed Ti. The improvement in bioactivity and a slight decrease in corrosion resistance can be attributed to the incomplete structure of hydroxyapatite nanorods when compared to MHTed Ti. Consequently, this work successfully achieved a hydroxyapatite-modified multilayered oxidized coating with gradient performance in term of bioactivity and corrosion resistance, establishing it as a promising candidate material for hard tissue repair.

A Review of the Application of Thermal Analysis in the Development of Bone Tissue Repair Materials

A Review of the Application of Thermal Analysis in the Development of Bone Tissue Repair Materials

Neonatal Tissue-derived Extracellular Vesicle Therapy (NEXT): A Potent Strategy for Precision Regenerative Medicine.

Extracellular vesicle (EV)-based therapies have emerged as a promising means in regenerative medicine. However, the conventional EV therapy strategy (using EVs from a single type of cultured cell) displays some limitations, such as inefficient EV production and lack of tissue-specific repair effects. Here, we report that neonatal tissue-derived EV therapy (NEXT) is a potent strategy for precision tissue repair. In brief, large amounts of EVs with higher yield/purity can be readily isolated from desired tissues with less production time/cost compared to the conventional cell culture-based method. Moreover, source factors, such as age and tissue type, can affect the repair efficacy of such tissue-derived EVs in different tissue injury models (skin wounds and acute kidney injury), and neonatal tissue-derived EVs show superior tissue repair potency compared with adult tissue-derived EVs. Different age- or tissue type-derived EVs have distinct composition (e.g., protein) signatures that are likely due to the diverse metabolic patterns of the donor tissues, which may contribute to the specific repair action modes of NEXT in different types of tissue injury. Furthermore, neonatal tissue-derived EVs can be incorporated with bioactive materials (e.g., artificial ECM hydrogel) for advanced tissue repair. This study highlights that our NEXT strategy may provide a new avenue for precision tissue repair in many types of tissue injury. This article is protected by copyright. All rights reserved.

Hybrid Materials for Tissue Repair and Replacement: Another Frontier in Biomaterial Exploitation Focusing on Cardiovascular and Urological Fields

The main purpose of tissue engineering is to fabricate and exploit engineered constructs suitable for the effective replacement of damaged tissues and organs to perfectly integrate with the host’s organism without eliciting any adverse reaction. Ideally, autologous materials represent the best option, but they are often limited due to the low availability of compatible healthy tissues. So far, one therapeutic approach relies on the exploitation of synthetic materials as they exhibit good features in terms of impermeability, deformability, and flexibility, but present chronic risks of infections and inflammations. Alternatively, biological materials, including naturally derived ones and acellular tissue matrices of human or animal origin, can be used to induce cells growth and differentiation, which are needed for tissue regeneration; however, this kind of material lacks satisfactory mechanical resistance and reproducibility, affecting their clinical application. In order to overcome the above-mentioned limitations, hybrid materials, which can be obtained by coupling synthetic polymers and biological materials, have been investigated with the aim to improve biological compatibility and mechanical features. Currently, the interest in these materials is growing, but the ideal ones have not been found yet. The present review aims at exploring some applications of hybrid materials, with particular mention to urological and cardiovascular fields. In the first case, the efforts to find a construct that can guarantee impermeability, mechanical resistance, and patency is herein illustrated; in the second case, the search for impermeability, hemocompatibility and adequate compliance is disclosed.

Regulating the multifactor during wet chemical synthesis to obtain calcium phosphate powders with controllable phase purity for bone repair

Calcium phosphate ceramics are widely used as bone repair materials owing to their excellent biocompatibility, bone conductivity, bone induction, and degradability. Although there are many methods for synthesizing calcium phosphate and controlling its phase composition, it is necessary to explore effective preparation methods by understanding the formation of calcium phosphate and its influencing factors. In this study, calcium phosphate powders with controllable phase compositions were synthesized using a wet chemical precipitation method by adjusting the process parameters (aging time, bipolar solution, initial Ca-P molar ratio, capping agent concentration, and system concentration). Subsequently, a certain biphasic proportion of (biphasic calcium phosphate, BCP) products was prepared, and pure (β-tricalcium phosphate, β-TCP) can be obtained according to the customer's requirements. BCP ceramics with desired phase compositions were obtained by pressing and sintering different calcium-deficient powders. Specifically, β-TCP powder with a purity of 99.83 wt% was obtained when the aging time, bipolar solution, initial Ca-P molar ratio, capping agent concentration, and system concentration were 0 h, 50% ethanol, 1, 0.27 M, and 0.0135 M, respectively. The BCP synthesized in this study shows great application potential in the field of bone tissue repair materials.