Tissue Scaffolds Research Articles

Advanced functional polymer materials for biomedical applications

AbstractPolymer structures are essential in biomedical applications due to their biocompatibility, biodegradability, and ability to form intricate structures on micro‐ to nanometer scales. This review, emphasizing electrospinning and phase inversion techniques, examines the fabrication strategies and chemical design of polymer structures for biomedical use. Electrospinning, particularly needleless electrospinning, produces nanofibres with high porosity and flexibility and is widely applied in tissue engineering and drug delivery. Phase inversion, including thermal, nonsolvent‐, vapor‐ and evaporation‐induced phase separation, allows precise control over polymer properties but faces challenges in terms of cooling rates and solvent characteristics. Chemical design through doping, functionalization, cross‐linking and copolymerization enhances the biocompatibility, biodegradability and mechanical properties of polymers, facilitating advanced applications in drug delivery, tissue scaffolding and biosensors. Advanced functional polymers are revolutionizing biomedical fields, offering innovative solutions for therapeutic medicine delivery, disease detection, diagnostics, and regenerative medicine. Despite remarkable progress, challenges, such as scalability, cost‐effectiveness, and environmental impact, persist. This review underscores the transformative potential of advanced polymer materials in medical treatments and advocates for continuous research and interdisciplinary collaboration to overcome existing challenges and fully exploit the capabilities of these materials in improving patient care and medical outcomes. Future perspectives highlight enhancing precision control mechanisms, integrating phase inversion with other techniques and developing large‐scale production methods to advance the field further.

Electrospinning Aligned SF/Magnetic Nanoparticles-Blend Nanofiber Scaffolds for Inducing Skeletal Myoblast Alignment and Differentiation.

In the realm of skeletal muscle tissue engineering, anisotropic materials that emulate natural tissues show substantial promise. Electrospun scaffolds, mimicking the fibrillar structure of the extracellular matrix, are commonly employed but often fall short in achieving optimal alignment and mechanical strength. Silk fibroin has emerged as a versatile material in tissue engineering, valued for its biocompatibility, mechanical robustness, and biodegradability. However, conventional electrospinning methods of SF result in randomly oriented fibers, limiting their efficacy. In this work, we developed a straightforward method to fabricate directional tissue scaffolds using silk fibroin. By integrating a magnetic field collecting device and incorporating Fe3O4 nanoparticles into the spinning solution, we successfully produced well-aligned silk nanofiber scaffolds. These aligned fibers not only improved scaffold orientation and mechanical properties but also exhibited magnetic responsiveness. The aligned SF scaffolds effectively guided the adhesion, proliferation, and differentiation of mesenchymal stem cells along the fiber direction. Cultured on these scaffolds, myoblast C2C12 cells demonstrated oriented growth, highlighting the potential of aligned SF fibers in advancing skeletal muscle engineering for biomedical applications.

Application of electrospinning and 3D-printing based bilayer composite scaffold in the skull base reconstruction during transnasal surgery

Skull base defects are a common complication after transsphenoidal endoscopic surgery, and their commonly used autologous tissue repair has limited clinical outcomes. Tissue-engineered scaffolds prepared by advanced techniques of electrostatic spinning and three-dimensional (3D) printing was an effective way to solve this problem. In this study, soft tissue scaffolds consisting of centripetal nanofiber mats and 3D-printed hard tissue scaffolds consisting of porous structures were prepared, respectively. And the two layers were combined to obtain bilayer composite scaffolds. The physicochemical characterization proved that the nanofiber mat prepared by polylactide-polycaprolactone (PLCL) electrospinning had a uniform centripetal nanofiber structure, and the loaded bFGF growth factor could achieve a slow release for 14 days and exert its bioactivity to promote the proliferation of fibroblasts. The porous scaffolds prepared with polycaprolactone (PCL), and hydroxyapatite (HA) 3D printing have a 300 μm macroporous structure with good biocompatibility. In vivo experiments results demonstrated that the bilayer composite scaffold could promote soft tissue repair of the skull base membrane through the centripetal nanofiber structure and slow-release of bFGF factor. It also played the role of promoting the regeneration of the skull base bone tissue. In addition, the centripetal nanofiber structure also had a promotional effect on the regeneration of skull base bone tissue.

3D Bioprinted Chondrogenic Gelatin Methacrylate-Poly(ethylene glycol) Diacrylate Composite Scaffolds for Intervertebral Disc Restoration

Abstract Degenerative spine pathologies, including intervertebral disc (IVD) degeneration, present a significant healthcare challenge due to their association with chronic pain and disability. This study explores an innovative approach to IVD regeneration utilizing 3D bioprinting technology, specifically visible light-based digital light processing (VL-DLP), to fabricate tissue scaffolds that closely mimic the native architecture of the IVD. Utilizing a hybrid bioink composed of gelatin methacrylate (GelMA) and poly(ethylene glycol) diacrylate (PEGDA) at a 10% concentration, we achieved enhanced printing fidelity and mechanical properties suitable for load-bearing applications such as the IVD. Preconditioning rat bone marrow-derived mesenchymal stem cell (rBMSC) spheroids with chondrogenic media before incorporating them into the GelMA-PEGDA scaffold further promoted the regenerative capabilities of this system. Our findings demonstrate that this bioprinted scaffold not only supports cell viability and integration but also contributes to the restoration of disc height in a rat caudal disc model without inducing adverse inflammatory responses. The study underscores the potential of combining advanced bioprinting techniques and cell preconditioning strategies to develop effective treatments for IVD degeneration and other musculoskeletal disorders, highlighting the need for further research into the dynamic interplay between cellular migration and the hydrogel matrix.

An in vivo screen for proteolytic switch domains that can mediate Notch activation by force.

Notch proteins are single pass transmembrane receptors activated by sequential extracellular and intramembrane cleavages that release their cytosolic domains to function as transcription factors in the nucleus. Upon binding, Delta/Serrate/LAG-2 (DSL) ligands activate Notch by exerting a "pulling" force across the intercellular ligand/receptor bridge. This pulling force is generated by Epsin-mediated endocytosis of ligand into the signal-sending cell, and results in the extracellular cleavage of the force-sensing Negative Regulatory Region (NRR) of the receptor by an ADAM10 protease [Kuzbanian (Kuz) in Drosophila ]. Here, we have used chimeric Notch and DSL proteins to screen for other domains that can function as ligand-dependent proteolytic switches in place of the NRR in the developing Drosophila wing. While many of the tested domains are either refractory to cleavage or constitutively cleaved, we identify several that mediate Notch activation in response to ligand. These NRR analogues derive from widely divergent source proteins and have strikingly different predicted structures. Yet, almost all depend on force exerted by Epsin-mediated ligand endocytosis and cleavage catalyzed by Kuz. We posit that the sequence space of protein domains that can serve as force-sensing proteolytic switches in Notch activation is unexpectedly large, a conclusion that has implications for the mechanism of target recognition by Kuz/ADAM10 proteases and is consistent with a more general role for force dependent ADAM10 proteolysis in other cell contact-dependent signaling mechanisms. Our results also validate the screen for increasing the repertoire of proteolytic switches available for synthetic Notch (synNotch) therapies and tissue engineering.

Nanozyme-enhanced enzyme control: Computational strategies for precise and sustained enzymatic activity in tissue engineering

Nanomaterials are revolutionizing tissue engineering by significantly enhancing enzyme-mediated chemical processes and cellular activities, thereby advancing the development of more effective therapeutic strategies. This research delves into the intricate dynamics of enzyme diffusion within tissue matrices, providing a comprehensive computational modeling framework aimed at optimizing enzyme concentration control in tissue scaffolds. Through advanced numerical algorithms and computational analysis, the study simulates optimal control strategies for regulating nanozyme levels, ensuring precise and sustained enzymatic activity within the scaffolds. A novel aspect of this work is the integration of videographic records, which offers an enriched understanding of the complex interactions between nanomaterials and biological tissues, providing detailed insights into the system’s operational dynamics. The study bridges the gap between experimental methodologies and theoretical models, aligning with the cutting-edge research in chemical physics and physical chemistry by offering novel approaches to tissue engineering challenges. The findings underscore the critical role of nanomaterials in achieving precise enzymatic control, which is pivotal for the development of advanced biomimetic systems and improved therapeutic outcomes. This work contributes to the ongoing frontier research in physical phenomena within chemistry, biology, and materials science, by providing significant new insights into enzyme delivery mechanisms and their application in biomedical contexts. The research not only highlights the importance of innovative methodologies in tissue engineering but also sets the stage for future experimental validations and potential clinical applications

Achieving biomimetic porosity and strength of bone in magnesium scaffolds through binder jet additive manufacturing

Magnesium (Mg) alloys are a promising candidate for synthetic bone tissue substitutes. In bone tissue engineering, achieving a balance between pore characteristics that facilitate biological functions and the essential stiffness required for load-bearing functions is extremely challenging. This study employs binder jet additive manufacturing to fabricate an interconnected porous structure in Mg alloys that mimics the microporosity and mechanical properties of human cortical bone types. Using scanning electron microscopy, micro-computed tomography, and mercury intrusion porosimetry, we found that the binder jet printed and sintered (BJPS) MgZnZr alloys possess an interconnected porous structure, featuring an overall porosity of 13.3 %, a median pore size of 12.7 μm, and pore interconnectivity exceeding 95 %. The BJPS MgZnZr alloy demonstrated a tensile strength of ~130 MPa, a yield strength of ~100 MPa, an elastic modulus of ~21.5 GPa, and an ultimate compressive strength of ~349 MPa. These values align with the ranges observed in human bone types and outperform those of porous Mg alloys produced using the other conventional and additive manufacturing methods. Moreover, the BJPS MgZnZr alloy showed level 0 cytotoxicity with a greater MC3T3-E1 cell viability, attachment, and proliferation when compared to a cast MgZnZr counterpart, since the highly interconnected 3D porous structure provides cells with an additional dimension for infiltration. Finally, we provide evidence for the concept of using binder jet additive manufacturing for fabricating Mg implants tailored for applications in hard tissue engineering, including craniomaxillofacial procedures, bone fixation, and substitutes for bone grafts. The results of this study provide a solid foundation for future advancements in digital manufacturing of Mg alloys for biomedical applications.

A modular approach to 3D-printed bilayer composite scaffolds for osteochondral tissue engineering

Prolonged osteochondral tissue engineering damage can result in osteoarthritis and decreased quality of life. Multiphasic scaffolds, where different layers model different microenvironments, are a promising treatment approach, yet stable joining between layers during fabrication remains challenging. To overcome this problem, in this study, a bilayer scaffold for osteochondral tissue regeneration was fabricated using 3D printing technology which containing a layer of PCL/hydroxyapatite (HA) nanoparticles and another layer of PCL/gelatin with various concentrations of fibrin (10, 20 and 30 wt.%). These printed scaffolds were evaluated with SEM (Scanning Electron Microscopy), FTIR (Fourier Transform Infrared Spectroscopy) and mechanical properties. The results showed that the porous scaffolds fabricated with pore size of 210–255 µm. Following, the ductility increased with the further addition of fibrin in bilayer composites which showed these composites scaffolds are suitable for the cartilage part of osteochondral. Also, the contact angle results demonstrated the incorporation of fibrin in bilayer scaffolds based on PCL matrix, can lead to a decrease in contact angle and result in the improvement of hydrophilicity that confirmed by increasing the degradation rate of scaffolds containing further fibrin percentage. The bioactivity study of bilayer scaffolds indicated that both fibrin and hydroxyapatite can significantly improve the cell attachment on fabricated scaffolds. The MTT assay, DAPI and Alizarin red tests of bilayer composite scaffolds showed that samples containing 30% fibrin have the more biocompatibility than that of samples with 10 and 20% fibrin which indicated the potential of this bilayer scaffold for osteochondral tissue regeneration.Graphical

Mechanical deviation in 3D-Printed PLA bone scaffolds during biodegradation

Large or carcinogenic bone defects may require a challenging bone tissue scaffold design ensuring a proper mechanobiological setting. Porosity and biodegradation rate are the key parameters controlling the bone-remodeling process. PLA presents a great potential for geometrically flexible 3-D scaffold design. This study aims to investigate the mechanical variation throughout the biodegradation process for lattice-type PLA scaffolds using both experimental observations and simulations. Three different unit-cell geometries are used for creating the scaffolds: basic cube (BC), body-centered structure (BCS), and body-centered cube (BCC). Three different porosity ratios, 50 %, 62.5 %, and 75 %, are assigned to all three structures by altering their strut dimensions. 3-D printed scaffolds are soaked in PBS solution at 37 °C for 15, 30, 60, 90, and 120 days both unloaded and under dead load. Water absorption, weight loss, and compression stiffness are measured to characterize the first-stage degradation and investigate the possible influences of these parameters on the whole biodegradation process. The strength reduction stage of biodegradation is simulated by solving pseudo-first-order kinetics-based molecular weight change equation using FEA with equisized cubic (voxel-like) elements.For the first stage, mechanical load does not have a statistically significant effect on biodegradation. BCC with 62.5 % porosity shows a maximum water absorption rate of around 25 % by the 60th day which brings an advantage in creating an aquatic environment for cell growth. Results indicate a significant water deposition inside almost all scaffolds and water content is determined to be the main reason for the retained or increased compression stiffness. A distinguishable stiffness increase in the initial degradation process occurs for 75 % porous BC and 50 % porous BCC scaffolds. Following the quasi-stable stage of biodegradation, almost all scaffolds lost their rigidity by around 44–48 % within 120 days based on numerical results. Therefore, initial stiffness increase in the quasi-stable stage of biodegradation can be advantageous and BCC geometry with a porosity between 50% and 62 % is the optimum solution for the whole biodegradation process.

Electrospun "Hard-Soft" Interpenetrating Nanofibrous Tissue Scaffolds Facilitating Enhanced Mechanical Strength and Cell Proliferation.

"Soft" hydrogel-based macroporous scaffolds have been widely used in tissue engineering and drug delivery applications due to their hydrated interfaces and macroporous structures, but have drawbacks related to their weak mechanics and often weak adhesion to cells. In contrast, "hard" poly(caprolactone) (PCL) electrospun fibrous networks have desirable mechanical strength and ductility but offer minimal interfacial hydration and thus limited capacity for cell proliferation. Herein, we demonstrate the fabrication of interpenetrating nanofibrous networks based on coelectrospun PCL and poly(oligoethylene glycol methacrylate) (POEGMA) nanofibers that exhibit the mechanical benefits of PCL but the interfacial hydration benefits of hydrogels. The electrospinning process results in partially aligned but interpenetrating fiber network with minimal internal phase separation, leading to anisotropic but strong mechanical properties even in the hydrated state; apparent ultimate tensile strengths of the swollen scaffolds ranged from 429 ± 39 kPa in the direction of fiber alignment (longitudinal) to 86 ± 25 kPa perpendicular to fiber alignment (cross-longitudinal), typical of PCL-based scaffolds and enabling efficient suture retention in different directions. However, contact angle measurements indicate hydrogel-like interfacial properties due to the presence of the interpenetrating POEGMA network. C2C12 myoblast proliferation in the PCL-POEGMA scaffolds was 50% higher than that observed on PCL-only scaffolds, a result attributed to the presence of the more hydrophilic POEGMA interpenetrating nanofiber network. Overall, this method is demonstrated to represent a facile single-step strategy to fabricate strong macroporous but still interfacially hydrophilic scaffolds for tissue engineering applications.

A biodegradable piezoelectric scaffold promotes spinal cord injury nerve regeneration

Neural repair and regeneration remain one of the greatest challenges in regenerative medicine. The incorporation of intelligent scaffolds with noninvasive in vivo electrical stimulation illustrates considerable potential for tissue repair and regeneration. Nevertheless, the development of biomaterials that possess both biodegradable tissue scaffolds and electrical stimulation capabilities at a high level remains a significant obstacle. In this study, we effectively integrated the organic piezoelectric material poly-L-lactic acid (PLLA) with inorganic piezoelectric nanowires (potassium sodium niobate coated with polydopamine, KNN@PDA) to fabricate PLLA/KNN@PDA piezoelectric composite fibers. These fibers exhibit in-situ electrical stimulation capabilities, rendering them suitable for direct application in living tissues. The PLLA/KNN@PDA piezoelectric composite fibers not only function as biodegradable scaffolds for regenerative tissue engineering and platforms for in-situ electrical stimulation to enhance dorsal root ganglion axon growth, proliferation, and neuronal differentiation but also serve as versatile scaffolds for broader tissue engineering applications. In the complete spinal cord transection rat model, the piezoelectric scaffold enabled the recovery of rat motor function, indicating its significant ability to promote tissue formation and regeneration. Therefore, combining biodegradable piezoelectric tissue scaffolds with in situ electrical stimulation has significant therapeutic advantages for spinal cord injury repair and may be extended to other damaged tissues regeneration.

Polyhydroxybutyrate/poly(ε‐caprolactone)‐based electrospun membranes loaded with amoxicillin‐potassium clavulanate halloysite nanotubes for biomedical applications

AbstractBiopolymers exhibit distinct properties for biomedical applications. Different biopolymer classes are utilized for various applications, for example antibacterial properties, drug delivery, tissue engineering, tissue scaffolds etc. In the present investigation, a nano‐bioengineering approach was followed to prepare polyhydroxybutyrate and polycaprolactone polymer‐based drug‐loaded halloysite nanotube electrospun membranes for biomedical applications. Functionalized halloysite nanotubes ((3‐aminopropyl)triethoxysilane acid treated halloysite nanotubes) at different weight percentages (1, 3, 5 and 7 wt%) were loaded with a broad‐spectrum antibiotic amoxicillin trihydrate‐potassium clavulanate, incorporated into the electrospun membranes, and characterized by different techniques such as XRD, FTIR, SEM, TEM and TGA. Different physical and mechanical properties were evaluated, such as porosity, water uptake, water vapor transmission rate, wettability and tensile properties. The developed membranes exhibited good in vitro biological properties, for example antibacterial, effective cell migration and less toxicity, as confirmed by disk diffusion, MTT (3‐(4,5‐dimethylthiazolyl‐2)‐2,5‐diphenyltetrazolium bromide) and cell scratch assays. A sustained drug release profile was observed from all the developed membranes. Overall results on the characterization of the developed membranes confirm the suitability of their use for different biomedical applications and as a wound dressing application. © 2024 Society of Chemical Industry.

Folic acid modified silver nanoparticles promote endothelialization and inhibit calcification of decellularized heart valves by immunomodulation with anti-bacteria property

Xenogeneic decellularized heart valves (DHVs) have become one of the most commonly used scaffolds for tissue engineered heart valves (TEHVs) due to extensive resources and possessing the distinct three-layer structure similar to native heart valves. However, DHVs as scaffolds face the shortages such as poor mechanical properties, proneness to thrombosis and calcification, difficulty in endothelialization and chronic inflammatory responses etc., which limit their applications in clinic. In this work, we constructed a novel TEHV with immunomodulatory functions by loading folic acid modified silver nanoparticles (FS NPs) on DHVs to overcome these issues. The FS NPs preferentially targeted M1 macrophages and reduced their intracellular H2O2 level, resulting in polarizing them into M2 phenotype. The increased M2 macrophages facilitated to eliminate inflammation, recruit endothelial cells, and promote their proliferation and endothelialization by secreting relative factors. We founded that FS NPs with the size of 80 nm modified DHVs (FSD-80) performed optimally on cytocompatibility and regulating macrophage phenotype ability in vitro. In addition, the FSD-80 had excellent mechanical properties, hemocompatibility and anti-bacteria property. The results of the subcutaneous implantation in rats revealed that the FSD-80 also had good performance in regulating macrophage phenotype, promoting endothelialization, remolding the extracellular matrix and anti-calcification in vivo. Therefore, FS NPs-loaded DHVs possess immunomodulatory functions, which is a feasible and promising strategy for constructing TEHVs with excellent comprehensive performance.

Fabricating Biodegradable Tissue Scaffolds Through a New Aggregation Triggered Physical Cross‐Linking Strategy of Hydrophilic and Hydrophobic Polymers

Fabricating Biodegradable Tissue Scaffolds Through a New Aggregation Triggered Physical Cross‐Linking Strategy of Hydrophilic and Hydrophobic Polymers

An optical system for cellular mechanostimulation in 3D hydrogels

We introduce a method utilizing single laser-generated cavitation bubbles to stimulate cellular mechanotransduction in dermal fibroblasts embedded within 3D hydrogels. We demonstrate that fibroblasts embedded in either amorphous or fibrillar hydrogels engage in Ca2+ signaling following exposure to an impulsive mechanical stimulus provided by a single 250 µm diameter laser-generated cavitation bubble. We find that the spatial extent of the cellular signaling is larger for cells embedded within a fibrous collagen hydrogel as compared to those embedded within an amorphous polyvinyl alcohol polymer (SLO-PVA) hydrogel. Additionally, for fibroblasts embedded in collagen, we find an increased range of cellular mechanosensitivity for cells that are polarized relative to the radial axis as compared to the circumferential axis. By contrast, fibroblasts embedded within SLO-PVA did not display orientation-dependent mechanosensitivity. Fibroblasts embedded in hydrogels and cultured in calcium-free media did not show cavitation-induced mechanotransduction; implicating calcium signaling based on transmembrane Ca2+ transport. This study demonstrates the utility of single laser-generated cavitation bubbles to provide local non-invasive impulsive mechanical stimuli within 3D hydrogel tissue models with concurrent imaging using optical microscopy. Statement of significanceCurrently, there are limited methods for the non-invasive real-time assessment of cellular sensitivity to mechanical stimuli within 3D tissue scaffolds. We describe an original approach that utilizes a pulsed laser microbeam within a standard laser scanning microscope system to generate single cavitation bubbles to provide impulsive mechanostimulation to cells within 3D fibrillar and amorphous hydrogels. Using this technique, we measure the cellular mechanosensitivity of primary human dermal fibroblasts embedded in amorphous and fibrillar hydrogels, thereby providing a useful method to examine cellular mechanotransduction in 3D biomaterials. Moreover, the implementation of our method within a standard optical microscope makes it suitable for broad adoption by cellular mechanotransduction researchers and opens the possibility of high-throughput evaluation of biomaterials with respect to cellular mechanosignaling.

Meniscal scaffolds based on self-healable elastomer-hydrogel composites with biomimetic structure and tribological properties for repairing meniscal injuries

Meniscal injuries are increasing dramatically with the aging of the population and the prevalence of sports. Tissue engineering technology is the most promising method for the treatment of meniscal injuries, but the preparation of long-term and durable meniscal scaffolds with mechanical and tribological properties like natural articular cartilage remains a great challenge. Here, inspired by the structure and lubrication mechanism of the meniscus, a durable meniscus scaffold with bionic 3D structure, self-lubrication, and intelligent drug release function is prepared. An elastomer-hydrogel composite consisting of a direct ink writing (DIW) printed elastomer skeleton and a hydrogel matrix is prepared for the meniscus scaffold. The bionic 3D structure of the scaffolds is realized by combining computer-aided structural design and 3D printing technology. The self-healing ability obtained by incorporating dynamic covalent bonds, and the robust interface achieved by co-curing of the elastomer and hydrogel resins, ensure the stability and durability of the composite meniscal scaffolds. Taking advantage of the coexistence of aqueous and oily phases in the emulsion-type hydrogel resin, a hydrophobic phospholipid is loaded into the hydrogel, and achieves excellent boundary lubrication of the composite through its fiction-response release and self-assembly. Moreover, the meniscus scaffolds enable intelligent drug release to adapt to the physiological characteristics during inflammation. In vivo tests in rabbit models validate the protective effect of the scaffold on cartilage. These methods and concepts provide a solid foundation for the preparation of bionic tissue scaffolds.

Preparation of Gradient HEA-DAC/HPA Hydrogels by Limited Domain Swelling Method.

Hydrogels are widely used in biological dressing, tissue scaffolding, drug delivery, sensors, and other promising applications owing to their water-rich soft structures, biocompatibility, and adjustable mechanical properties. However, most of the conventional hydrogels are isotropic. The anisotropic structures existed widely in the organizational structure of plants and animals, which played a crucial role in biological systems. In this work, a method of limited domain swelling to prepare anisotropic hydrogels is proposed. Through spatially controlled swelling, the extension direction of hydrogels can be limited by a tailored mold, further achieving anisotropic hydrogels with concentration gradients. The external solution serves as a swelling solution to promote swelling and extension of the hydrogel matrix in a mold which can control the extension direction. Due to the diversity of external solutions, the method can be applied to prepare a variety of stimulus-responsive polymers. The limited domain swelling method is promising for the construction of anisotropic hydrogels with different structures and properties.

One-step synthesis of a piezoelectric hybrid BNNT/BaTiO3 composite and its application in bone tissue engineering

Nanomaterials with piezoelectric properties can significantly improve the applicability of polymers used in tissue engineering applications. In this study, we report the one-step synthesis of a novel hybrid piezoelectric composite comprising barium titanates and boron nitride nanotubes. This composite is distinguished by its unique microstructures, including nanoflakes, triangular boron nitride structures, and fiber-like boron nitride nanotube configurations, which contribute to its enhanced piezoelectric properties. The composite was incorporated into a chitosan-based tissue scaffold and evaluated in vitro. Electric-responsive Human Osteoblast cells cultured on the scaffolds are exposed to low-frequency ultrasound stimulation during cell growth. The biocompatibility, cell adhesion, alkaline phosphatase activities, and mineralization of osteoblast cells on the piezo-composite scaffolds were evaluated. The results show that the hybrid piezoelectric composite significantly enhances the properties of chitosan-based scaffold.

Chitosan-Peptide Composites for Tissue Engineering Applications: Advances in Treatment Strategies.

One of the most well-known instances of an interdisciplinary subject is tissue engineering, where experts from many backgrounds collaborate to address important health issues and improve people's quality of life. Many researchers are interested in using chitosan and its derivatives as an alternative to fabricating scaffold engineering and skin grafts in tissue because of its natural abundance, affordability, biodegradability, biocompatibility, and wound healing properties. Nanomaterials based on peptides can provide cells with the essential biological cues required to promote cellular adhesion and are easily fabricated. Due to such worthy properties of chitosan and peptide, they find their application in tissue engineering and regeneration processes. The implementation of hybrids of chitosan and peptide is increasing in the field of tissue engineering and scaffolding for improved cellular adherence and bioactivity. This review covers the individual applications of peptide and chitosan in tissue engineering and further discusses the role of their conjugates in the same. Here, the recent findings are also discussed, along with studies involving the use of these hybrids in tissue engineering applications.

A 3D hydrogel scaffold with adjustable interlayer spacing for the formation of compact myocardial tissue

AbstractThe design and optimization of three‐dimensional tissue scaffolds have presented a persistent challenge for myocardial tissue engineering. While current scaffolds have made strides in mimicking in vivo three‐dimensional environments, the presence of interlayer spacing has limited the formation of densely packed tissue, impeding cell‐to‐cell connections. We proposed a novel dynamic three‐dimensional myocardial tissue engineering scaffold with adjustable interlayer spacing, aiming to improve the uniformity of cell distribution and facilitate effective cell communication. The device was composed of hydrogel scaffolds that were fabricated with poly (ethylene glycol) diacrylate (PEGDA) and flexible elastomer actuators that composed of polyurethane acrylate (PUA). Human induced pluripotent stem cell‐derived cardiomyocytes mixed with gelatin methacryloyl (GelMA) were seeded onto the multi‐layered scaffold with initial spacing of 100–500 μm. Experimental results indicated the seeding efficiency was maximized at an initial spacing of 400 μm. By decreasing the interlayer spacing, cell growth morphology and gap junction protein expression was improved. This work demonstrated the effect of interlayer spacing modulation to the tissue density and provided a potential approach for cultivation of compact and multi‐layered myocardial tissue.