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The use of electrospun nanofibers to create a supportive scaffold for cell growth and tissue development has attracted intensive interest in the field of tissue engineering. In this study, a conjugated electrospinning system was designed and employed to fabricate a series of different polycaprolactone (PCL) scaffolds simultaneously containing both of microfibers and nanofibers. SEM images conformed the successful formation of micro-/nano- fibers in one scaffold by adjusting the polymeric concentrations. The PCL concentration was found to have dramatic effects on the diameter of as-generated fibers, and the mean diameter and crystallinity of electrospun PCL fibers decreased with the decreasing of PCL concentration, resulting in much lower mechanical properties. Compared with the pure PCL microfiber-constructed scaffold, the PCL micro-/nano- fiber scaffolds exhibited obviously decreased mean pore size, increased porosity. Interestingly, the PCL micro-/nano- fiber scaffolds were found to exhibit significantly increased Young's modulus and ultimate stress than both of PCL nanofiber scaffold and PCL microfiber scaffold. In vitro cell characterization results indicated that the introduction of nanoscale fibers significantly enhanced cell adhesion, and proliferation of PCL micro-/nano- fiber scaffolds. Moreover, this enhancement became more pronounced as the average diameter of the nanoscale fibers decreased. Overall, our present study provides an effective strategy for generating PCL micro-/nano- fiber scaffolds with more appropriate structure and properties, which show great potential for tissue engineering application. [ABSTRACT FROM AUTHOR]

Background: The advent of tissue engineering and regenerative medicine has introduced innovative approaches to treating degenerative and traumatic injuries, particularly in cartilage, a tissue with limited self-repair capabilities. Among the various stem cell sources, umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have garnered significant interest due to their non-invasive collection, minimal ethical concerns, and robust regenerative potential, particularly in cartilage regeneration. Methods: A comprehensive literature review was conducted using multiple databases, including PubMed, Scopus, Web of Science, and Google Scholar. Search terms focused on "umbilical cordderived mesenchymal stromal cells," "chondrogenesis," "cartilage regeneration," and related topics. Studies published in the past two decades were included, with selection criteria emphasizing methodological rigor and relevance to UC-MSC chondrogenesis. The review synthesizes findings from various sources to provide a thorough analysis of the potential of UC-MSCs in cartilage tissue engineering. Results: UC-MSCs exhibit significant chondrogenic potential, supported by their ability to differentiate into chondrocytes under specific conditions. Recent advancements include the development of biomaterial scaffolds and the application of genetic engineering techniques, such as CRISPR/Cas9, to enhance chondrogenic differentiation. Despite these advancements, challenges remain in standardizing cell isolation techniques, scaling up production for clinical use, and ensuring the long-term functionality of regenerated cartilage. Conclusion: UC-MSCs offer a promising solution for cartilage regeneration in the field of regenerative medicine. Ongoing research is focused on overcoming current challenges through the use of advanced technologies, including bioreactors and gene editing. Collaborative efforts among researchers, clinicians, and bioengineers are essential to translating the potential of UC-MSCs into effective clinical therapies, which could significantly advance tissue regeneration and therapeutic innovation. [ABSTRACT FROM AUTHOR]

Purpose: Cardiac tissue engineering is suggested as a promising approach to overcome problems associated with impaired myocardium. This is the first study to investigate the use of BC and gelatin for cardiomyocyte adhesion and growth. Methods: Bacterial cellulose (BC) membranes were produced by Komagataeibacter xylinus and coated or mixed with gelatin to make gelatin-coated BC (BCG) or gelatin-mixed BC (mBCG) scaffolds, respectively. BC based-scaffolds were characterized via SEM, FTIR, XRD, and AFM. Neonatal rat-ventricular cardiomyocytes (nr-vCMCs) were cultured on the scaffolds to check the capability of the composites for cardiomyocyte attachment, growth and expansion. Results: The average nanofibrils diameter in all scaffolds was suitable (~ 30–65 nm) for nr-vCMCs culture. Pore diameter (≥ 10 µm), surface roughness (~ 182 nm), elastic modulus (0.075 ± 0.015 MPa) in mBCG were in accordance with cardiomyocyte requirements, so that mBCG could better support attachment of nr-vCMCs with high concentration of gelatin, and appropriate surface roughness. Also, it could better support growth and expansion of nr-vCMCs due to submicron scale of nanofibrils and proper elasticity (~ 0.075 MPa). The viability of nr-vCMCs on BC and BCG scaffolds was very low even at day 2 of culture (~ ≤ 40%), but, mBCG could promote a metabolic active state of nr-vCMCs until day 7 (~ ≥ 50%). Conclusion: According to our results, mBCG scaffold was the most suitable composite for cardiomyocyte culture, regarding its physicochemical and cell characteristics. It is suggested that improvement in mBCG stability and cell attachment features may provide a convenient scaffold for cardiac tissue engineering. [ABSTRACT FROM AUTHOR]

Polylactic acid/chitosan (PLA/CS) and poly(vinyl alcohol)/chitosan (PVA/CS) are considered potential blends for use in tissue engineering, since when obtained in the form of 3D fibers they can form structures with high porosity, biocompatibility, antimicrobial activity and morphology similar to tissues and organs. However, there is a scarce number of reports in the literature addressing the production of systems based on 3D fibrous mixtures of PVA or PLA with high chitosan amount because of the difficulty in spinning CS into stable structures using acidic solutions, and without further employment of cross-linking agents. Therefore, this work focused on a novel procedure to prepare 3D fibrous structures of PVA and PLA with high chitosan content, combining the solution blow spinning technique, a heated air environment and the use of eco-friendly solvents, without using crosslinking agents. The influence of CS incorporation on the as-prepared structures was assessed by scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, contact angle measurement, porosity, swelling and degradation tests. Rheological tests evidenced that an increase in the CS content implies a greater viscosity of the spinning solutions, hindering the fibrillar structures formation. Fibers produced showed a randomly interconnected and highly porous fibrous cotton-wool-like structure, with fiber diameters ranging from 481 to 637 nm for PVA/CS systems, and from 1276 to 2050 nm for PLA/CS systems. A decrease in the thermal stability of the blend-based fibers and an increase in hydrophilicity, porosity, swelling and in vitro biodegradation were observed in the blend systems. Results indicate that the obtained fibrillar structures possess morphological and physical characteristics that may be interesting for application as 3D fibrous scaffolds in tissue engineering. [ABSTRACT FROM AUTHOR]

Since the introduction of 3D printing to biomedical fields, numerous advancements have been achieved in tissue engineering due to the advantages it offers. However, 3D-printed polymeric scaffolds may lack certain properties, impacting their functionality and success, such as bioactivity and cell affinity. In this study, the dip coating method was employed to enhance the biological and mechanical properties of 3D-printed polylactic acid (PLA) scaffolds using fused deposition modeling (FDM) technology. Specifically, the scaffolds were dip-coated with a polyvinyl alcohol (PVA)/nano-diopside solution. The thermal features of the 3D-printed scaffolds were analyzed using the differential scanning calorimetry method, revealing a calculated crystallinity of about 13%. To assess bioactivity, both coated and non-coated scaffolds were immersed in simulated body fluid (SBF) for 28 days, and their evaluation was conducted through scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDAX). At 40 °C, compared to the thermal conductivity of the nanofluid, the thermal conductivities of the non-coated 3D-printed sample and the coated 3D-printed sample were reduced by 9.91 and 22.52%, respectively. The results of this study guided the design and fabrication of improved tissue engineering scaffolds for bone regeneration applications. [ABSTRACT FROM AUTHOR]

Tissue engineering is a set of techniques for producing or reconstructing tissue that primarily aims to restore or improve the function of tissues in the human body. The aim of the present study was to evaluate the mechanical and histological characteristics of decellularized tracheal scaffolds prepared in comparison with fresh trachea for use in tracheal repair. In order to prepare the scaffold, sheep's trachea was prepared and after cleaning the waste tissues, they were decellularized. Then decellularized scaffolds were evaluated histologically and laboratory and numerical study of the nonlinear mechanical behavior of tracheal tissue and scaffold and their comparison. Examining the results of histological evaluations showed that the decellularization of the scaffolds was completely done. These results were confirmed by hematoxylin–eosin staining. Also, the exact hyperelastic properties of tracheal tissue and scaffold were used in biomechanical models, and according to the presented results, the five-term Mooney–Rivlin strain energy density function became a suitable behavioral model for modeling the hyperelastic behavior of trachea and scaffold. In total, the results of this research showed that the scaffolds obtained from decellularization by preserving the main compositions of the desired tissue can be a suitable platform for investigating cell behaviors. [ABSTRACT FROM AUTHOR]

This study investigates the synthesis of hydroxyapatite nanoparticles via aqueous precipitation at pH 9 and Ca/P molar ratio of 1.67, exploring the effects of various synthesis parameters. Moreover, porous hydroxyapatite scaffolds were created using a pore-forming agent. These parameters' effects on the crystal structure, chemical composition, morphology, porosity, and pore size of hydroxyapatite powders and porous scaffolds were determined by various analytical techniques such as x-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), simultaneous thermal analysis (TGA/DSC), electron microscopy (SEM), pycnometry, and optical microscopy (OM). The XRD results revealed good crystallization of the hydroxyapatite with the formation of TCP and TTCP secondary phases resulting from the decomposition of hydroxyapatite (HA). The FTIR spectra of sintered HA confirmed the presence of the main absorption bands corresponding to phosphate and hydroxide groups with different peaks in intensity. The TGA/DSC analysis confirmed the results previously obtained by FTIR and XRD. SEM analysis showed the formation of various shapes of hydroxyapatite nanoparticles. According to different synthesis parameters, a porous HA scaffold up to 61% porosity can be prepared using ammonium bicarbonate as a pore-forming agent. [ABSTRACT FROM AUTHOR]

Bacterial nanocellulose (BNC) possesses unique properties that make it an appealing biomaterial for various biomedical applications. However, its potential in dentistry has not been broadly investigated. This paper provides a comprehensive overview of the potential applications of BNC in dentistry, including the design of implants, scaffolds, wound dressing materials, oral and bone tissue repair, drug delivery systems, and antimicrobial BNC composites. BNC has emerged as a promising biomaterial for various applications in dentistry. Benefiting from its numerous properties, BNC is widely used in hard and soft tissue engineering, particularly in the design of scaffolds, implants, and membranes. Additionally, BNC is suitable as a wound dressing for wounds, including intraoral lesions such as aphthous stomatitis and other mucosal ulcers. Furthermore, BNC can be employed in drug delivery systems. BNC's use in performing surgical and endodontic treatments, as well as in manufacturing nanocomposites that promote bone mineralization in the dental periapical area, guided bone regeneration (GBR), and periodontal scaffolds and membranes, has been limited. Moreover, BNC has been applied to improve dental material characteristics and silicate cements leading to the development of practical, novel composites in this field. In addition to these application areas, future research could consider the development of antibaterial composites using BNC and the execution of clinical trials assessing their role as adjunctive treatments for periodontal diseases in dentistry. [ABSTRACT FROM AUTHOR]

Subcutaneous delivery of cell therapy is an appealing minimally-invasive strategy for the treatment of various diseases. However, the subdermal site is poorly vascularized making it inadequate for supporting engraftment, viability, and function of exogenous cells. In this study, we developed a 3D bioprinted scaffold composed of alginate/gelatin (Alg/Gel) embedded with mesenchymal stem cells (MSCs) to enhance vascularization and tissue ingrowth in a subcutaneous microenvironment. We identified bio-ink crosslinking conditions that optimally recapitulated the mechanical properties of subcutaneous tissue. We achieved controlled degradation of the Alg/Gel scaffold synchronous with host tissue ingrowth and remodeling. Further, in a rat model, the Alg/Gel scaffold was superior to MSC-embedded Pluronic hydrogel in supporting tissue development and vascularization of a subcutaneous site. While the scaffold alone promoted vascular tissue formation, the inclusion of MSCs in the bio-ink further enhanced angiogenesis. Our findings highlight the use of simple cell-laden degradable bioprinted structures to generate a supportive microenvironment for cell delivery. [ABSTRACT FROM AUTHOR]

Extrusion-based three-dimensional (3D) printing of gelatin (Gel) is crucial for fabricating bone tissue engineering scaffolds via additive manufacturing. However, the thermal instability of Gel remains a persistent challenge, as it tends to collapse at mild temperatures. Current approaches often involve simply mixing Gel particles with various materials, resulting in biomaterial inks that lack uniformity and have inconsistent degradation characteristics. In this study, acetic acid was used to dissolve Gel and polycaprolactone (PCL) separately, producing homogeneous Gel/PCL dispersions with optimal pre-treatment performance. These dispersions were then combined and hybridized with nano-hydroxyapatite (n-HA) to create a composite printing ink. By evaluating the printability of the ink, the optimal conditions were identified: a n-HA concentration of 50% (w/w), a printing temperature of 10–15 ℃, a printing pressure of 2.5 bar, and a printing speed of 7 mm/s. The resulting biomaterial inks, with a composition of 25% Gel, 25% PCL, and 50% n-HA, demonstrated excellent printability and stability, along with significantly enhanced mechanical properties. As a result, 3D scaffolds with high printability and shape fidelity can be printed at room temperature, followed by deep freezing at -80 ℃ and cross-linking with vanillin. The Gel-based composite scaffolds demonstrated excellent biocompatibility, cell adhesion, cell viability and nano-hydroxyapatite absorption in vitro. Additionally, in vivo experiments revealed that the bioactive scaffold biodegraded during implantation and significantly promoted bone regeneration at the defect site. This provides a promising strategy for treating bone defects in clinical setting. In conclusion, the Gel/PCL/n-HA biomaterial inks presented here offer an innovative solution for extrusion bioprinting in the field of bone tissue engineering. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we attempted to create skeletal muscle sheets made of directly converted myoblasts (dMBs) with a nanogel scaffold on a biosheet using a mouse gastroschisis model. Methods: dMBs were prepared by the co-transfection of MYOD1 and MYCL into human fibroblasts. Silicon tubes were implanted under the skin of NOG/SCID mice, and biosheets were formed. The nanogel was a nanoscale hydrogel based on cholesterol-modified pullulan, and a NanoClip-FD gel was prepared by freeze-drying the nanogel. 7 mm in length was created in the abdominal wall of NOG/SCID mice as a mouse gastroschisis model. Matrigel or NanoCliP-FD gel seeded with dMBs was placed on the biosheet and implanted on the model mice. Results: Fourteen days after surgery, dMBs with Matrigel showed a small amount of coarse aggregations of muscle-like cells. In contrast, dMBs with NanoCliP-FD gel showed multinucleated muscle-like cells, which were expressed as desmin and myogenin by fluorescent immunostaining. Conclusion: Nanogels have a porous structure and are useful as scaffolds for tissue regeneration by supplying oxygen and nutrients supply to the cells. Combining dMBs and nanogels on the biosheets resulted in the differentiation and engraftment of skeletal muscle, suggesting the possibility of developing skeletal muscle sheets derived from autologous cells and tissues. [ABSTRACT FROM AUTHOR]

Soft tissue engineering has focused on green, solvent-free biopolymers with rubber-like characteristics. One of the well-known elastomeric polyesters is polyglycerol sebacate (PGS). The present investigation involves the synthesis of a novel biopolymer composed of PGS-co-poly(ε-caprolactone) (PCL) copolymer, alongside hydroxyapatite (HA) using bovine bone. These synthesized materials were utilized to build scaffolds using 18–22 kV electrospinning. By in situ polymerization, PGS-co-PCL/HA nanocomposites with 5% and 10% hydroxyapatite nanoparticles were developed. Various analysis such as FTIR, TGA, SEM, and DSC were utilized to examine the prepared samples. Introducing 10% HA to the PGS-co-PCL copolymer blends boosted nanocomposite mechanical strength by 300%. Meanwhile, PGS-co-PCL-based samples and their nanocomposites demonstrated promising biocompatibility and antibacterial characteristics. Biodegradability experiments revealed that at pH 7, PGS-co-PCL-HA10% was degraded by 45% within 30 days, whereas at pH 11, degradation accelerated to 65%. This study's findings provide a novel approach for soft tissue engineers to construct effective scaffolds with great biocompatibility and enhanced mechanical properties by combining PGS with co-PCL and adding HA nanoparticles. [ABSTRACT FROM AUTHOR]

Purpose: To assess the use of bone marrow aspirate (BM) and bone marrow aspirate concentrate (BMAC) in the treatment of long-bone nonunion and to understand mechanism of action. Methods: A systematic review of PubMed and EBSCOHost was completed to identify studies that investigated the use of BM or BMAC for the diagnosis of delayed union and/or nonunion of long-bone fractures. Studies of isolated bone marrow-mesenchymal stem cells (BM-MSCs) and use in non-long-bone fractures were excluded. Statistical analysis was confounded by heterogeneous fracture fixation methods, treatment history, and scaffold use. Results: Our initial search yielded 430 publications, which was screened down to 25 studies. Successful treatment in aseptic nonunion was reported at 79–100% (BM) and 50–100% (BMAC). Septic nonunion rates were slightly better at 73–100% (BM) and 83.3–100% (BMAC). 18/24 studies report union rates > 80%. One study reports successful treatment of septic nonunion with BMAC and no antibiotics. A separate study reported a significant reduction in autograft reinfection rate when combined with BMAC (P = 0.009). Major adverse events include two deep infections at injection site and one case of heterotopic ossification. Most studies note transient mild donor site discomfort and potential injection site discomfort attributed to needle size. Conclusion: The current literature pertaining to use of BM/BMAC for nonunion is extremely heterogeneous in terms of patient population and concomitant treatment modalities. While results are promising for use of BM/BMAC with other gold standard treatment methodologies, the literature requires additional Level I data to clarify the impact of role BM/BMAC in treating nonunion when used alone and in combination with other modalities. Level of evidence: Level III. [ABSTRACT FROM AUTHOR]

Conventional methods have failed to show the ability of articular cartilage to completely restore. Decellularized extracellular matrix has achieved interest as a potential biomaterial for cartilage tissue engineering approaches. The decellularized cartilage-derived matrix (CDM) scaffolds retain the native composition of cartilage tissue, providing a conducive microenvironment for cellular growth and differentiation, while exhibit limited mechanical support. Our investigation involved the fabrication of a new hybrid CDM- polyvinyl alcohol (PVA) hydrogel scaffold with four different concentrations (5%, 10%, 15%, and 20%), followed by a comprehensive characterization of the construct's physicochemical, mechanical, and biological properties to elucidate their potential in cartilage regeneration applications. Our results demonstrated that hybridization of the CDM with PVA enhanced the mechanical properties besides ensuring biocompatibility. FTIR and DSC results also confirmed the mechanical improvements in hybrid scaffolds. The hybrid CDM/PVA (15%/5%, 15%/10%, 15%/15%, and 15%/20%) scaffolds showed significantly different compressive strengths (p < 0.0001, p < 0.0004, p < 0.0001, p < 0.012 respectively). Moreover, resazurin test showed cell attachment and growth on all four types of hybrid scaffolds during seven days of three dimensional culture. The cross-linked CDM15%/PVA5% group, demonstrated acceptable mechanical strength, pore size, physicochemical properties, swelling behavior, and cell growth and attachment. Our data indicate that our hybrid CDM/PVA scaffold possess bioactive properties suitable for a promising candidate for cartilage tissue engineering studies. [ABSTRACT FROM AUTHOR]

A significant obstacle in bone tissue engineering is the creation of biodegradable bone replacements with the requisite mechanical and biological capabilities to treat more severe and intricately shaped injuries. Baghdadite has recently indicated that active biological ions such as silicon (Si4+) and zirconium (Zr4+) have been proven to increase bone growth considerably. In this study, we produced 3D-printed PCL-based scaffolds containing different amounts of Baghdadite using the robocasting solvent technique. Notably, PCL with 40 and 60 wt.% Baghdadite scaffolds (PB40 and PB60) promoted a more biomimetic environment for in vitro bone growth as their proper bioactivity and cell viability results were obtained without the addition of osteoinductive components. The printing process produced 3D scaffolds with a compressive strength of 7.94 MPa and elastic modulus of 29.95 MPa in PB40. According to the analytical prediction models in PB40, the elastic modulus was 24.7 and 26.89 MPa. Also, adding 60 wt.% Baghdadite increased the degradation rate to 5.1% in two months, more than six times that of PCL-based scaffolds. Cell proliferation assay demonstrated that the optical density of MG63 cells after 7 days of culture increased from 1.43 ± 0.03 to 1.82 ± 0.20 in PB40 as compared to pure PCL scaffold. Furthermore, bioactivity evaluation, ion release assessment, and morphological observation results further revealed that incorporating Baghdadite into a 3D-printed PCL-based scaffold could improve bone regeneration. Our findings demonstrate that the PCL/Baghdadite composite scaffold may be efficiently manufactured using 3D-printing technology and is extremely promising for bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

In recent years, people have had more expectations from the developed technology in medicine, especially in the field of orthopedics and traumatology. Tissue engineers are interested in techniques that benefit from patients' cells and biomaterials, instead of prostheses and implants. On the other hand, researchers have begun to use various medicinal plants for regeneration and anti-cancer studies. In the present study, we aimed to produce cartilage and bone inductive scaffolds for osteochondral tissue engineering applications with the addition of hawthorn or elderberry extracts. Firstly, wet electro-spun poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid) fibers were integrated with a loofah mat. Then, they were impregnated into chitosan solution with/without hawthorn or elderberry extract. Composite hydrogel scaffolds were obtained by cross-linking with 0.3% (w/v) genipin. Fabricated scaffolds had more than 90% porosity and showed swelling capacity in the range of 1500–2200%. Based on the in vitro biocompatibility analyses using mesenchymal stem cells (MSCs), all the fabricated scaffolds were found to be biocompatible by WST-1, ALP activity, and GAG content analysis. Also, histological/immunohistochemical analyses showed that hawthorn and elderberry extract addition increased MSCs proliferation and collagen type I and II positivity. Consequently, all the scaffolds showed promising features for osteochondral tissue engineering applications. [ABSTRACT FROM AUTHOR]

Decellularization of plant tissues is an emerging route to fabricate scaffolds for tissue engineering and regenerative medicine. Although significant progress has been made in the field of plant tissue decellularization, functionalization of plant scaffolds is still an emerging field, and loading them with L-ascorbic acid to promote skin regeneration has not yet been reported. L-ascorbic acid is an antioxidant that plays a key role in collagen synthesis as a cofactor of lysyl hydroxylase and prolyl hydroxylase. It has been shown to have significant importance in physiological wound healing by stimulating fibroblasts to produce collagen at both the molecular and the genetic levels. In this work, we aimed to fabricate an ascorbic acid-releasing bioactive scaffold by introducing a stable form of ascorbic acid, L-ascorbic acid 2-phosphate (AA2P), into decellularized baby spinach leaves and investigated its biological activity in vitro. Our results demonstrated that AA2P could be easily introduced into decellularized baby spinach leaf scaffolds and subsequently released within the effective dose range. AA2P-releasing baby spinach leaves were found to increase metabolic activity and enhance collagen synthesis in L929 fibroblasts after 21 days. In conclusion, this study demonstrated the fabrication of a novel functionalized skin tissue engineering scaffold and made a significant contribution to the fields of plant decellularization and skin tissue engineering. [ABSTRACT FROM AUTHOR]

Advanced therapeutic dressings are the current research interest that achieves rapid and complete wound healing. The healing of skin wounds demonstrates a remarkable cellular function process that is distinct in nature and involves the interaction of various cells, growth factors, and cytokines. In this study, nanofibrous scaffolds were prepared using poly(ε-caprolactone) and polylactic acid as mat scaffolds. Also, copper nanoparticles (CuNPs) and curcumin were added to fabricate a hybrid nanocomposite scaffold using the electrospinning technique. The fabricated scaffolds were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), tensile analysis, porosity, and water vapor transmission rate. SEM analysis proved the nanostructured fibers have suitable porosity without any beads. The presence of CuNPs in the PCL-Cu nanofibrous mat was confirmed by TEM analysis. The tensile test confirmed an increase and decrease in the elongation ratio by CuNPs and curcumin addition, respectively. The biocompatibility and cell attachment to the nanofibers were proved by MTT and DAPI staining which proved a significantly positive effect of curcumin in the cell growth. The scaffold can hinder both the gram-negative and gram-positive bacteria through direct contact with them. This research study showed that the addition of CuNPs and curcumin in the hybrid nanocomposite scaffold compensates for each other's shortcomings and has the potential to be used in wound healing applications. [ABSTRACT FROM AUTHOR]

Previously, we reported successful cellular expansion of a murine colorectal carcinoma cell line (CT-26) using a three-dimensional (3D) engineered extracellular matrix (EECM) fibrillar scaffold structure. CCL-247 were grown over a limited time period of 8 days on 3D EECM or tissue culture polystyrene (TCPS). Cells were then assayed for growth, electroporation efficiency and Vigil manufacturing release criteria. Using EECM scaffolds, we report an expansion of CCL-247 (HCT116), a colorectal carcinoma cell line, from a starting concentration of 2.45 × 105 cells to 1.9 × 106 cells per scaffold. Following expansion, 3D EECM-derived cells were assessed based on clinical release criteria of the Vigil manufacturing process utilized for Phase IIb trial operation with the FDA. 3D EECM-derived cells passed all Vigil manufacturing release criteria including cytokine expression. Here, we demonstrate successful Vigil product manufacture achieving the specifications necessary for the clinical trial product release of Vigil treatment. Our results confirm that 3D EECM can be utilized for the expansion of human cancer cell CCL-247, justifying further clinical development involving human tissue sample manufacturing including core needle biopsy and minimal ascites samples. [ABSTRACT FROM AUTHOR]

Tissue engineering aims at producing in the laboratory new biological tissues by combining cells, scaffold materials, and biochemistry. Recent successes in the field are promising, but sustainability and reproducibility issues still limit the large-scale applications of this technique. The present work addresses the development of a computational model that describes cell motility in biodegradable hydrogel scaffolds. The goal is to support the understanding and the control of the first stage of tissue formation, when cells seeded into the scaffold congregate to form clusters, necessary precursors of tissue blocks. Cellular migration is treated as an advective/diffusive process modeled via the phase-field approach. The chemo-biological mechanisms incorporated in the modeling framework are: (i) the natural degradation of the hydrogel; (ii) chemotaxis induced by cell-cell signaling pathways; (iii) nutrient diffusion through the construct and its consumption by cells. Each cell initially moves following a random path, subsequently switching to a directed chemically-driven motion when the presence of other cells is sensed in its neighborhood. Numerical results highlight the role of the interplay between nutrient availability in the construct, chemoattractant production, scaffold degradation and cell motility, showing that the proposed model could pave the way towards efficient computationally-aided tools for the optimization of neotissue mass production. [ABSTRACT FROM AUTHOR]

Background: In bone tissue engineering segment, numerous approaches have been investigated to address critically sized bone defects via 3D scaffolds, as the amount of autologous bone grafts are limited, accompanied with complications on harvesting. Moreover, the use of bone-marrow-derived stem cells is also a limiting factor owing to the invasive procedures involved and the low yield of stem cells. Hence, research is ongoing on the search for an ideal bone graft system promoting bone growth and regeneration. Purpose of the Study: This study aims to develop a unique platform for tissue development via stem cell differentiation towards an osteogenic phenotype providing optimum biological cues for cell adhesion, differentiation and proliferation using biomimetic gelatin-based scaffolds. The use of adipose-derived mesenchymal stem cells in this study also offers an ideal approach for the development of an autologous bone graft. Methods: A gelatin-vinyl acetate-based 3D scaffold system incorporating Bioglass was developed and the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs) on the highly porous freeze-dried gelatin-vinyl acetate/ Bioglass scaffold (GB) system was analyzed. The physicochemical properties, cell proliferation and viability were investigated by seeding rat adipose tissue-derived mesenchymal stem cells (ADSCs) onto the scaffolds. The osteogenic differentiation potential of the ADMSC seeded GeVAc/bioglass system was assessed using calcium deposition assay and bone-related protein and genes and comparing with the 3D Gelatin vinyl acetate coppolymer (GeVAc) constructs. Results and Conclusion: According to the findings, the 3D porous GeVAc/bioglass scaffold can be considered as a promising matrix for bone tissue regeneration and the 3D architecture supports the differentiation of the ADMSCs into osteoblast cells and enhances the production of mineralized bone matrix. [ABSTRACT FROM AUTHOR]

This study investigates recent advancements in drug delivery systems (DDS) for tissue engineering, emphasizing their role in the targeted and sustained release of therapeutic agents to promote tissue regeneration. It explores innovative approaches, including nanotechnology, 3D printing, and immunomodulation, which enhance the effectiveness of tissue engineering therapies. This review provides a brief overview of the fundamentals of controlled drug delivery, comparing controlled release and slow release. It also introduces drug delivery vehicles, drug release mechanisms, release kinetics, and recent applications in the field of regenerative medicine. It highlights the benefits of nanotechnology, such as increased drug loading capacity and stability, and identifies 3D-printed scaffolds as a promising method for sustained drug release. Additionally, the growing interest in using DDS for immunomodulation to improve tissue regeneration is discussed. The rapidly evolving field of DDS in tissue engineering presents new opportunities for developing more effective therapeutic strategies. This study contributes to the understanding of these innovations and their potential applications. [ABSTRACT FROM AUTHOR]

Electrospun nanofiber scaffolds mimic the structure of the natural extracellular matrix, making them promising for application in tissue engineering. Based on this, the biopolymers poly(ε-caprolactone) (PCL) and gelatin, with good mechanical and biological properties, respectively, were electrospun with acetic acid as the only solvent, without the crosslinking process in order to reduce the cytotoxic effects of commonly used solvents. This study evaluated the influence of scaffold thicknesses on the physicochemical properties. Scaffolds with 4 different thicknesses were produced by increasing the electrospinning time (A = 1 h, B = 1.5 h, C = 2 h and D = 3 h). Thicker scaffolds (B, C and D, 0.142 ± 0.029 to 0.306 ± 0.053 nm) were manipulated easily, presented higher mechanical strength (from 156.21 to 178.53%) and smaller diameter fibers (approximately 300.0 nm). On the other hand, the longer the processing time, the less uniform the fibers and more melting regions between fibers, which may hinder the use of the scaffold and should be considered. Only the thickest scaffold (D) showed higher wettability (contact angle 31.1° ± 3°). Intermediate thickness scaffolds showed less beads and fiber irregularities. Cell adhesion was good due to gelatin, though cell proliferation remained constant for the thicker scaffold indicating that longer processing time may not be advantageous for cell application. Results showed that intermediate thickness scaffolds of PCL/gelatin (0.142 ± 0.029 to 0.195 ± 0.034 nm) assure good physicochemical properties to be applied for different cell types. [ABSTRACT FROM AUTHOR]

Novel scaffolds of chitosan-reduced functionalized graphene oxide (CH-rfGO) containing different values of hydroxyapatite nanoparticles (npHA) were prepared. npHA was synthesized and rfGO was obtained by the reduction and functionalization of single-layer GO nanosheets. The CH-rfGO scaffolds containing 0, 0.5, 1 and 1.5 g HA were fabricated by freeze-drying technique. The properties of the synthesized materials and the fabricated scaffolds were investigated using FTIR, XRD, FESEM and the rheology analyzer. The compressive strength, pore size and thickness of the pore walls of the scaffolds were measured. According to the FTIR and XRD results, rfGO and npHA were successfully synthesized. The interactions between HA and CH-rfGO were confirmed by XRD. The prepared scaffolds were superhydrophilic and highly porous with a hemispherical morphology that was interconnected. HA significantly changed the porous structure, pore size and pore wall thickness of scaffolds. HA increased the pore wall thickness, but the pore size first increased and then decreased; the average values were 80–230 µm (for 0, 0.5 and 1.5 HA) and 230–480 µm (for 1 HA). With regard to the rheological behavior of the slurries, the behavior of shear thinning was observed. The viscosity and shear stress changed with HA, being highest for the 1 HA sample. HA significantly improved the compressive strength of the scaffolds, reaching 963 kPa for 1.5 HA. [ABSTRACT FROM AUTHOR]

Bone tissue engineering provides a promising strategy for the treatment of bone defects. Nonetheless, the clinical utilization of biomaterial-based scaffolds is constrained by their inadequate mechanical strength and absence of osteo-inductive properties. Here, we proposed to endow nano-scaffold (NS) constructed by coaxial electrospinning technique with enhanced osteogenic bioactivities and mechanical properties by incorporating biocompatible magnetic iron oxide nanoparticles (IONPs) and icaritin (ICA). Four types of nano-scaffolds (NS, ICA@NS, NS-IONPs and ICA@NS-IONPs) were prepared. The incorporation of ICA and IONPs minimally impact their surface morphological and chemical properties. IONPs enhanced the mechanical properties of NS scaffolds, including hardness, tensile strength, and elastic modulus. In vitro assessments demonstrated that ICA@NS-IONPs exhibited enhanced osteogenic bioactivities towards mouse calvarial pre-osteoblast cell line MC3T3-E1 as evidenced by detecting the alkaline phosphatase (ALP) activity level, expressions of osteogenesis-related genes and proteins as well as mineralized nodule formation. Mechanistic investigations revealed that MEK/ERK (MAP kinase-ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK)) signaling pathway could offer a plausible explanation for the osteogenic differentiation of MC3T3-E1 cells induced by ICA@NS-IONPs. Furthermore, the implantation of nano-scaffolds in rat skull defects exhibited a substantial improvement in in vivo bone regeneration. Therefore, IONPs and ICA incorporated coaxial electrospinning nano-scaffolds present a novel strategy for the optimization of scaffolds for bone tissue engineering. [ABSTRACT FROM AUTHOR]

In the context of tissue engineering, biofabrication techniques are employed to process cells in hydrogel-based matrices, known as bioinks, into complex 3D structures. The aim is the production of functional tissue models or even entire organs. The regenerative production of biological tissues adheres to a multitude of criteria that ultimately determine the maturation of a functional tissue. These criteria are of biological nature, such as the biomimetic spatial positioning of different cell types within a physiologically and mechanically suitable matrix, which enables tissue maturation. Furthermore, the processing, a combination of technical procedures and biological materials, has proven highly challenging since cells are sensitive to stress, for example from shear and tensile forces, which may affect their vitality. On the other hand, high resolutions are pursued to create optimal conditions for subsequent tissue maturation. From an analytical perspective, it is prudent to first investigate the printing behavior of bioinks before undertaking complex biological tests. According to our findings, conventional shear rheological tests are insufficient to fully characterize the printing behavior of a bioink. For this reason, we have developed optical methods that, complementarily to the already developed tests, allow for quantification of printing quality and further viscoelastic modeling of bioinks. [ABSTRACT FROM AUTHOR]

Highlights: This review provides a comprehensive summary associated with recent progress in the preparation and application of microgels. The characteristics and applications of microgels and microgel-based scaffolds for cell culture and delivery are elaborated with an emphasis on the advantages of these carriers in cell therapy. This review expounds on the ongoing and foreseeable applications and current limitations of microgels and their aggregate in the field of biomedical engineering. Through stimulating innovative ideas, the present review paves new avenues for expanding the application of microgels in cell delivery techniques. Microgels prepared from natural or synthetic hydrogel materials have aroused extensive attention as multifunctional cells or drug carriers, that are promising for tissue engineering and regenerative medicine. Microgels can also be aggregated into microporous scaffolds, promoting cell infiltration and proliferation for tissue repair. This review gives an overview of recent developments in the fabrication techniques and applications of microgels. A series of conventional and novel strategies including emulsification, microfluidic, lithography, electrospray, centrifugation, gas-shearing, three-dimensional bioprinting, etc. are discussed in depth. The characteristics and applications of microgels and microgel-based scaffolds for cell culture and delivery are elaborated with an emphasis on the advantages of these carriers in cell therapy. Additionally, we expound on the ongoing and foreseeable applications and current limitations of microgels and their aggregate in the field of biomedical engineering. Through stimulating innovative ideas, the present review paves new avenues for expanding the application of microgels in cell delivery techniques. [ABSTRACT FROM AUTHOR]

Chemobrionic systems have attracted great attention in material science for development of novel biomimetic materials. This study aims to design a new bioactive material by integrating biosilica into chemobrionic structure, which will be called biochemobrionic, and to comparatively investigate the use of both chemobrionic and biochemobrionic materials as bone scaffolds. Biosilica, isolated from Amphora sp. diatom, was integrated into chemobrionic structure, and a comprehensive set of analysis was conducted to evaluate their morphological, chemical, mechanical, thermal, and biodegradation properties. Then, the effects of both scaffolds on cell biocompatibility and osteogenic differentiation capacity were assessed. Cells attached to the scaffolds, spread out, and covered the entire surface, indicating the absence of cytotoxicity. Biochemobrionic scaffold exhibited a higher level of mineralization and bone formation than the chemobrionic structure due to the osteogenic activity of biosilica. These results present a comprehensive and pioneering understanding of the potential of (bio)chemobrionics for bone regeneration. [ABSTRACT FROM AUTHOR]

3D printing technology is a powerful tool in scaffold engineering for biomedical applications, especially in anticancer activities and drug delivery. The present study developed a 3D-printed gelatin–alginate scaffold incorporating letrozole-loaded niosomes (Let/Nio@Gel-AL-SC) as a more effective drug delivery system. The findings showed that the fabricated niosomes appeared spherical. 3D-printed scaffolds exhibited biodegradability and sustained drug-release properties. The drug release from the scaffold was less prominent under acidic conditions than physiological ones. Cytotoxicity analysis showed that the engineered Let/Nio@Gel-AL-SC scaffold exhibited significant cytotoxicity against MCF-7 cancer cells. Gene expression analysis demonstrated a significant decrease in the expression of BCL2, CCND1, MMP2, and CDK4 genes and a notable increase in the expression of BAX and P53 genes, as well as the activity of Caspase 3/7 enzyme following treatment with Let/Nio@Gel-AL-SC. In addition, flow cytometry analysis revealed that Let/Nio@Gel-AL-SC significantly reduced necrosis and dramatically increased apoptosis. Also, the Let/Nio@Gel-AL-SC formulation exhibited a significantly greater increase in ROS values. The incorporation of letrozole-loaded niosomes into 3D printing gelatin/alginate scaffold has enhanced the efficacy of anticancer therapy. This is demonstrated by the sustained release of drugs, which indicates a promising potential for effective anticancer activity. Consequently, this combination holds promise as a potential future cancer therapy strategy. [ABSTRACT FROM AUTHOR]

Recently, 3D-printed biodegradable scaffolds have shown great potential for bone repair in critical-size fractures. The differentiation of the cells on a scaffold is impacted among other factors by the surface deformation of the scaffold due to mechanical loading and the wall shear stresses imposed by the interstitial fluid flow. These factors are in turn significantly affected by the material properties, the geometry of the scaffold, as well as the loading and flow conditions. In this work, a numerical framework is proposed to study the influence of these factors on the expected osteochondral cell differentiation. The considered scaffold is rectangular with a 0/90 lay-down pattern and a four-layered strut made of polylactic acid with a 5% steel particle content. The distribution of the different types of cells on the scaffold surface is estimated through a scalar stimulus, calculated by using a mechanobioregulatory model. To reduce the simulation time for the computation of the stimulus, a probabilistic machine learning (ML)-based reduced-order model (ROM) is proposed. Then, a sensitivity analysis is performed using the Shapley additive explanations to examine the contribution of the various parameters to the framework stimulus predictions. In a final step, a multiobjective optimization procedure is implemented using genetic algorithms and the ROM, aiming to identify the material parameters and loading conditions that maximize the percentage of surface area populated by bone cells while minimizing the area corresponding to the other types of cells and the resorption condition. The results of the performed analysis highlight the potential of using ROMs for the scaffold design, by dramatically reducing the simulation time while enabling the efficient implementation of sensitivity analysis and optimization procedures. [ABSTRACT FROM AUTHOR]

Macrophages play a prominent role in tissue development, homeostasis, and repair. In addition, their fundamental and well-known functions are integral to the host's defense system, including immune responses and debris removal from apoptotic cells. These immune cells are remarkably responsive to various stimuli in the microenvironment, inducing multiple forms of differentiation with distinct phenotypes and roles. These stimuli comprise biochemical signals and physical biomaterial properties. Thus, understanding how immune cells differentiate is crucial for designing biomaterials, tissue scaffolds, implantable materials, and regenerative medicine, such as developing new drugs and immunomodulatory drug delivery systems. This review discusses about the latest techniques in inducing immune cell differentiation. [ABSTRACT FROM AUTHOR]

Acrylated epoxidized soybean oil (AESO) is a soybean oil derivative recently utilized as a green raw material in biopolymer synthesis. However, its potential as a photo-polymerizable feedstock in multifunctional tissue engineering scaffolds remains underexplored. While AESO exhibits strong biocompatibility, its rapid biodegradation and limited mechanical properties constrain its biomedical applications. Here, we present antibacterial scaffolds using polyvinylidene fluoride (PVDF), AESO, curcumin, and graphene oxide (GO) with high potential for tissue engineering applications. Our results showed that the scaffolds possess a semi-crystalline structure and the presence of PVDF could effectively support the mechanical integrity of the AESO phase. Fabricated scaffolds presented Young's modulus, ultimate tensile strength, and elongation at break of 105–250 MPa, 8–10 MPa, and 17–25%, respectively, that could fulfill the requirements for supporting a range of stiff tissues. Curcumin-containing scaffolds demonstrated desirable antibacterial activity against both E. coli and S. aureus bacteria. As well the capacity of the PVDF/AESO matrix for drug release was studied. As expected, hydrophilicity and biodegradation rates were influenced noticeably by incorporating GO nanosheets. Finally, the fabricated scaffold showed in-vitro biocompatibility with desirable attachment and proliferation of MG-63 cells. Our findings indicate the potential of AESO for tissue engineering and regenerative medicine applications. The employing of AESO in this study inspires the investigation of other plant oils and their derivatives as resins for fabricating biomedical scaffolds. [ABSTRACT FROM AUTHOR]

Purpose: Based on the clinical need for grafts for vascular tissue regeneration, our group developed a customizable scaffold derived from the human amniotic membrane. Our approach consists of rolling the decellularized amniotic membrane around a mandrel to form a multilayered tubular scaffold with tunable diameter and wall thickness. Herein, we aimed to investigate if silica nanoparticles (SiNP) could enhance the adhesion of the amnion layers within these rolled grafts. Methods: To test this, we assessed the structural integrity and mechanical properties of SiNP-treated scaffolds. Mechanical tests were repeated after six months to evaluate adhesion stability in aqueous environments. Results: Our results showed that the rolled SiNP-treated scaffolds maintained their tubular shape upon hydration, while non-treated scaffolds collapsed. By scanning electron microscopy, SiNP-treated scaffolds presented more densely packed layers than untreated controls. Mechanical analysis showed that SiNP treatment increased the scaffold's tensile strength up to tenfold in relation to non-treated controls and changed the mechanism of failure from interfacial slipping to single-point fracture. The nanoparticles reinforced the scaffolds both at the interface between two distinct layers and within each layer of the extracellular matrix. Finally, SiNP-treated scaffolds significantly increased the suture pullout force in comparison to untreated controls. Conclusion: Our study demonstrated that SiNP prevents the unraveling of a multilayered extracellular matrix graft while improving the scaffolds' overall mechanical properties. In addition to the generation of a robust biomaterial for vascular tissue regeneration, this novel layering technology is a promising strategy for a number of bioengineering applications. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing is an emerging technology for the construction of complex 3D constructs used for tissue engineering applications. In this study, we are proposing the preparation of 3D printing hydrogel inks consisting of the synthetic polymers poly(caprolactone) and poly(lactic acid), the biopolymer chitosan, and naturally derived gelatin. In addition, pluronic F-127 was used to improve the miscibility between the hydrophobic and hydrophilic components due to its amphiphilic character, as well as for its good 3D printability. The printability of the hydrogel inks was optimized by varying the composition, the extrusion nozzle, and the temperature, while the integrity of the 3D scaffolds was secured via sol–gel transition. The produced hydrogels with PCL-pluronic-chitosan-gelatin/15-20-4-2 wt% (PC3.75-Pl5-CG) and PLA-pluronic-chitosan-gelatin/10-20-4-2 wt% (PL2.5-Pl5-CG) presented the best printability, producing smooth and uniform porous scaffolds. The prepared hydrogels were formed via the interactions between the polymers through hydrogen bonding. Additionally, the produced hydrogels exhibited temperature-dependent swelling behavior, and the scaffolds with PCL presented lower swelling capacity than the scaffolds with PLA. The produced scaffolds presented slower hydrolyzation rate in simulated body fluid (SBF) at 25 °C compared to 37 °C. Biological studies proved that the 3D-printed porous scaffolds were non-cytotoxic and promoted human adipose-derived mesenchymal stem cell adhesion. [ABSTRACT FROM AUTHOR]

In the field of metal-based bone tissue engineering scaffolds, porous Zn-based scaffolds are expected to be one of the most promising biodegradable bone tissue engineering scaffolds due to their acceptable biocompatibility and more suitable degradation rate compared with Mg-based and Fe-based scaffolds. However, the poor mechanical strength of porous pure Zn scaffolds limits their clinical applications. To improve the mechanical properties of porous Zn scaffolds, alloying treatment has become a feasible method. In this work, porous Zn-Mg-Y alloy scaffolds were prepared by an air pressure infiltration (API) method using NaCl particles as spacing holders. The phase structures, microstructures, compressive mechanical properties, degradation properties, antibacterial abilities as well as cytotoxicity of the obtained porous Zn-Mg-Y alloy scaffolds were investigated. The experimental results suggest that the alloy scaffolds contain strengthening phases such as MgZn2 and/or Mg2Zn11 as well as Y-rich phases. Under the action of these strengthening phases, the porous Zn-Mg-Y alloy scaffolds exhibit better mechanical properties. In vitro degradation tests indicate that the strengthening phases such as MgZn2 and Mg2Zn11 in the alloy scaffolds can be preferentially degraded as sacrificial anodes. Correspondingly, the degradation rates of the porous Zn-Mg-Y alloy scaffolds in simulated body fluid (SBF) have been accelerated. Antibacterial tests imply that the porous Zn-Mg-Y alloy scaffolds possess excellent antibacterial ability against Escherichia coli similar to the porous pure Zn scaffolds. Cytotoxicity tests show that the Zn2+ concentrations in the 100% extracts prepared from the porous Zn-Mg-Y alloy scaffolds (not including Zn-3Mg-0.5Y alloy scaffold) were all lower than that prepared from the porous pure Zn scaffold. The 25% and 10% extracts prepared from all the porous Zn-Mg-Y alloy scaffolds exhibit excellent cellular activity on MC3T3-E1 cells. In summary, the porous Zn-Mg-Y alloy scaffolds have the potential to be used as bone tissue engineering scaffolds to withstand relatively large loads. [ABSTRACT FROM AUTHOR]

Cultivated meat (CM) offers a sustainable and ethical alternative to conventional animal agriculture, involving cell maturation in a controlled environment. To emulate the structural complexity of traditional meat, the development of animal-free and edible scaffolds is crucial, providing vital physical and biological support during tissue development. The aligned vascular bundles of the decellularised asparagus scaffold were selected to facilitate the attachment and alignment of murine myoblasts (C2C12) and porcine adipose-derived mesenchymal stem cells (pADMSCs). Muscle differentiation was assessed through immunofluorescence staining with muscle markers, including Myosin heavy chain (MHC), Myogenin (MYOG), and Desmin. The metabolic activity of Creatine Kinase in C2C12 differentiated cells significantly increased compared to proliferated cells. Quantitative PCR analysis revealed a significant increase in Myosin Heavy Polypeptide 1 (MYH1) and MYOG expression compared to Day 0. These results highlight the application of decellularised plant scaffold (DPS) as a promising, edible material conducive to cell attachment, proliferation, and differentiation into muscle tissue. To create a CM prototype with biological mimicry, pADMSC-derived muscle and fat cells were also co-cultured on the same scaffold. The co-culture was confirmed through immunofluorescence staining of muscle markers and LipidTOX staining, revealing distinct muscle fibres and adipocytes containing lipid droplets respectively. Texture profile analysis conducted on uncooked CM prototypes and pork loin showed no significant differences in textural values. However, the pan-fried CM prototype differed significantly in hardness and chewiness compared to pork loin. Understanding the scaffolds' textural profile enhances our insight into the potential sensory attributes of CM products. DPS shows potential for advancing CM biomanufacturing. [ABSTRACT FROM AUTHOR]

Tissue engineering offers a promising alternative therapy for myocardial infarction, which is associated with high mortality rates. Meanwhile, excellent biocompatibility and conductivity are indispensable features of cardiac tissue engineering scaffolds that facilitate electrical signal transmission between cardiomyocytes. In this study, 2,2,6,6-tetramethylpiperidine-1-oxy (TEMPO) -oxidized cellulose nanofibers (TOCN) were crosslinked by iron ions, then polymerized with pyrrole monomer to obtain in situ polymerized polypyrrole nanocellulose composite hydrogel scaffolds for myocardial tissue engineering. The composite hydrogel exhibited mechanical properties (50 ~ 75 kPa) and electrical conductivity (5 × 10–5 S·cm−1 ~ 1 × 10–3 S·cm−1) that match those of natural myocardial tissue, while it was non-cytotoxic (relative growth rate > 90%) and biocompatibility. At the same time, cells cultured on the TOCN-PPy scaffold showed increased expression of myocardial specific proteins such as connexin 43 and cardiac troponin T. Thus, the TOCN-PPy composite hydrogel showed a broad application prospect in the field of myocardial tissue engineering scaffold. [ABSTRACT FROM AUTHOR]

Restoring the physiological function of the damaged skin is crucial due to its undeniable protective role as well as its aesthetic aspects. Herein, a novel bilayer freeze-dried scaffold comprised of allograft collagen and glycosaminoglycan (Col-GAG; the biocompatible inner layer) adhered to silicone (mechanically reinforcing component) utilizing gelatin as the bio-glue was prepared to benefit from each origin (human-derived and synthetic) advantages. The structural characterizations of the scaffolds were analyzed by X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), tensile stress test, water uptake behavior, and Water Vapor Permeability (WVP). Also, the scaffolds' cytocompatibility was assessed by culturing human dermal fibroblasts (HDF) on the samples. Furthermore, the in vivo functionality was performed by implanting the scaffolds in male mice and observing the cellularization as well as neovascularization by Hematoxylin and Eosin (H&E) staining and CD31 marker. Based on the results, the potentially amorphous scaffolds were three-dimensional (3D) porous with randomly oriented interconnected pores suitable for cellular ingrowth. The application of the silicone layer resulted in resisting the extra osmotic pressure of water molecules by decreasing the water uptake ratio to 59.2 ± 0.33%, maintaining the WVP at an approximate rate of 0.1–10 mg/cm2hr, and boosting the tensile strength to 1.66 ± 0.12 MPa. The grafts provided an optimum environment for cell attachment and presented cellular viability upper than 70% after 72h. In vivo assessment exhibited improved perivascular localization, with the cell migration rate approximating 64%. The outcomes indicated that the achieved scaffold holds promise as an ideal wound dressing. [ABSTRACT FROM AUTHOR]

Recycled duck bones (DBs) and fish shells were processed into natural derivatives. Through innovative design, these natural derivatives were then combined with biocompatible polymer to create a new type of ecofriendly filament suitable for three-dimensional (3D) printing of scaffolds for bone regeneration. The DBs and fish shells were thermally processed to produce DB-derived hydroxyapatite (HA) and fish shell-derived Ca(OH)2 (TAS), respectively. Poly(ε-caprolactone) (PCL), HA, and TAS were combined and fabricated into new composite filaments, which were then transformed into scaffolds using 3D printing technology. The structure and antibacterial behaviors of the obtained composite scaffolds were studied. Alone, PCL showed no bacterial inhibition. MHA (a mix of 4, 8, 12, 16 wt%-HA and 0.8 wt% TAS) was added to PCL to form a PCL/MHA composite material, which significantly improved the functional properties of PCL and enhanced cell attachment and proliferation. The Ca(OH)2 content of TAS was responsible for the antibacterial effect. The PCL/MHA composites were porous and displayed enhanced osteoblast proliferation in vitro. The osteoblast cell population do not affected when cultured on the PCL/HA and PCL/MHA series composites according to cell cycle distribution analysis. The surfaces of the various PCL/HA and PCL/MHA composites showed elevated levels of calcium and phosphorus compounds when exposed to simulated body fluids. Calcium and phosphate ions were rapidly deposited on PCL/HA and PCL/MHA composite scaffolds in osteoblasts according to the cell mineralization assay. Our findings suggest great potential of the PCL/HA and PCL/MHA composite scaffolds in bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

Recent advancements in the field of biomedical engineering have underscored the pivotal role of biodegradable materials in addressing the challenges associated with tissue regeneration therapies. The spectrum of biodegradable materials presently encompasses ceramics, polymers, metals, and composites, each offering distinct advantages for the replacement or repair of compromised human tissues. Despite their utility, these biomaterials are not devoid of limitations, with issues such as suboptimal tissue integration, potential cytotoxicity, and mechanical mismatch (stress shielding) emerging as significant concerns. To mitigate these drawbacks, our research collective has embarked on the development of protein-based composite materials, showcasing enhanced biodegradability and biocompatibility. This study is dedicated to the elaboration and characterization of an innovative suture fabricated from human serum albumin through an extrusion methodology. Employing a suite of analytical techniques—namely tensile testing, scanning electron microscopy (SEM), and thermal gravimetric analysis (TGA)—we endeavored to elucidate the physicochemical attributes of the engineered suture. Additionally, the investigation extends to assessing the influence of integrating biodegradable organic modifiers on the suture's mechanical performance. Preliminary tensile testing has delineated the mechanical profile of the Filament Suture (FS), delineating tensile strengths spanning 1.3 to 9.616 MPa and elongation at break percentages ranging from 11.5 to 146.64%. These findings illuminate the mechanical versatility of the suture, hinting at its applicability across a broad spectrum of medical interventions. Subsequent analyses via SEM and TGA are anticipated to further delineate the suture's morphological features and thermal resilience, thereby enriching our comprehension of its overall performance characteristics. Moreover, the investigation delves into the ramifications of incorporating biodegradable organic constituents on the suture's mechanical integrity. Collectively, the study not only sheds light on the mechanical and thermal dynamics of a novel suture material derived from human serum albumin but also explores the prospective enhancements afforded by the amalgamation of biodegradable organic compounds, thereby broadening the horizon for future biomedical applications. [ABSTRACT FROM AUTHOR]

Biomedical engineering breakthroughs and increased patient expectations and requests for more comprehensive care are propelling the field of regenerative dentistry forward at a fast pace. Stem cells (SCs), bioactive compounds, and scaffolds are the mainstays of tissue engineering, the backbone of regenerative dentistry. Repairing damaged teeth and gums is a significant scientific problem at present. Novel therapeutic approaches for tooth and periodontal healing have been inspired by tissue engineering based on mesenchymal stem cells (MSCs). Furthermore, as a component of the MSC secretome, extracellular vesicles (EVs) have been shown to contribute to periodontal tissue repair and regeneration. The scaffold, made of an artificial extracellular matrix (ECM), acts as a supporting structure for new cell development and tissue formation. To effectively promote cell development, a scaffold must be non-toxic, biodegradable, biologically compatible, low in immunogenicity, and safe. Due to its promising biological characteristics for cell regeneration, dental tissue engineering has recently received much attention for its use of natural or synthetic polymer scaffolds with excellent mechanical properties, such as small pore size and a high surface-to-volume ratio, as a matrix. Moreover, as a bioactive material for carrying MSC-EVs, the combined application of scaffolds and MSC-EVs has a better regenerative effect on dental diseases. In this paper, we discuss how MSCs and MSC-derived EV treatment may be used to regenerate damaged teeth, and we highlight the role of various scaffolds in this process. The potential of utilizing mesenchymal stem cells (MSCs) and their derivatives (MSC-EVs) inserted into the scaffold to regenerate dental diseases is illustrated in this figure. Synthetic and natural scaffolds transport these cells to facilitate their safe and targeted delivery to the intended tissue. [ABSTRACT FROM AUTHOR]

Urethral stricture caused by various reasons has threatened the quality of life of patients for decades. Traditional reconstruction methods, especially for long-segment injuries, have shown poor outcomes in treating urethral strictures. Tissue engineering for urethral regeneration is an emerging concept in which special designed scaffolds and seed cells are used to promote local urethral regeneration. The scaffolds, seed cells, various factors and the host interact with each other and form the regenerative microenvironment. Among the various interactions involved, vascularization and fibrosis are the most important biological processes during urethral regeneration. Mesenchymal stem cells and induced pluripotent stem cells play special roles in stricture repair and facilitate long-segment urethral regeneration, but they may also induce carcinogenesis and genomic instability during reconstruction. Nevertheless, current technologies, such as genetic engineering, molecular imaging, and exosome extraction, provide us with opportunities to manage seed cell-related regenerative risks. In this review, we described the interactions among seed cells, scaffolds, factors and the host within the regenerative microenvironment, which may help in determining the exact molecular mechanisms involved in urethral stricture regeneration and promoting clinical trials and the application of urethral tissue engineering in patients suffering from urethral stricture. [ABSTRACT FROM AUTHOR]

The fabrication of scaffolds that mimic the structure of extracellular matrix molecules using electrospinning has great potential for various tissue engineering applications because it is advantageous for cell ingrowth and tissue formation. In particular, in the case of non-adhesive scaffolds, tissue adhesives (e.g., fibrin, glutaraldehyde) that provide strong adhesion to tissue surfaces or cells are sometimes used to efficiently utilize the desired function. Therefore, scaffolds that combine the advantages of adhesive materials while maintaining cell growth and functionality could further expand tissue engineering applications. In the present study, we developed nanofibers with greatly improved adhesive ability by blended cellulose acetate and levan, a bioadhesive polymer. Nanofibers manufactured through electrospinning exhibited stable mechanical properties through citric acid cross-linking and exhibited excellent adhesive performance with an adhesion strength of up to 3.67 MPa. In future research, we aim to expand the utility of bioadhesive nanofibers by loading nanofiber scaffolds with useful substances for diagnostic and therapeutic purposes. [ABSTRACT FROM AUTHOR]

Bioprinting, or bio-additive manufacturing, is a critical emerging field for transforming tissue engineering regenerative medicine to produce biological constructs and scaffolds in a layerwise fashion. Geometric accuracy and spatial distribution of scaffold porosity are critical factors associated with the quality of bio-printed tissue scaffolds. Determining optimal process parameters for tissue scaffold microextrusion 3D printing by traditional trial-and-error approaches is costly, labor-intensive, and time-consuming. In addition, effective in-process sensing techniques are needed to observe internal multilayer scaffold structures, such as porosity. Therefore, an in-process sensing platform based on integrated light scanning and microscopy was proposed to acquire in-process layer information during the fabrication of polymeric and hydrogel scaffolds. This work implements a customized sensing platform consisting of a 3D scanner and digital microscope for in-process quality monitoring of tissue scaffold biofabrication that provides in situ characterization of each printed layer's quality conditions (e.g., porosity). The proposed sensor-based in-process quality monitoring system can accurately capture layerwise porosity quality. Design of experiments (DoE) experimental analysis yielded a set of optimal process parameters that significantly improved the geometric accuracy and compressive modulus of thermoplastic- and hydrogel-based tissue scaffolds. The developed sensing system coupled with the DoE approach enables effective process parameter optimization to fabricate porous 3D-printed tissue scaffolds. It can significantly improve the quality and reproducibility of research associated with porous 3D-printed products, such as tissue scaffolds and membranes. [ABSTRACT FROM AUTHOR]

Purpose: The limited availability of autologous vessels for vascular bypass surgeries is a major roadblock to treating severe cardiovascular diseases. Based on this clinical priority, our group has developed a novel engineered vascular graft by rolling human amniotic membranes into multilayered extracellular matrixes (ECM). When treated with silica nanoparticles (SiNP), these rolled scaffolds showed a significant improvement in their structural and mechanical properties, matching those from gold standard autologous grafts. However, it remained to be determined how cells respond to SiNP-treated materials. As a first step toward understanding the biocompatibility of SiNP-dosed biomaterials, we aimed to assess how endothelial cells and blood components interact with SiNP-treated ECM scaffolds. Methods: To test this, we used established in vitro assays to study SiNP and SiNP-treated scaffolds' cyto and hemocompatibility. Results: Our results showed that SiNP effects on cells were concentration-dependent with no adverse effects observed up to 10 μg/ml of SiNP, with higher concentrations inducing cytotoxic and hemolytic responses. The SiNP also enhanced the scaffold's hydrophobicity state, a feature known to inhibit platelet and immune cell adhesion. Accordingly, SiNP-treated scaffolds were also shown to support endothelial cell growth while preventing platelet and leukocyte adhesion. Conclusion: Our findings suggest that the addition of SiNP to human amniotic membrane extracellular matrixes improves the cyto- and hemocompatibility of rolled scaffolds and highlights this strategy as a robust mechanism to stabilize layered collagen scaffolds for vascular tissue regeneration. [ABSTRACT FROM AUTHOR]

The fluid flow dynamics on the porous scaffolds and their static responses on the adjacent bone are very crucial parameters for bone adaptation. Researchers are trying to develop different algorithms to design biomimetic porous scaffolds incorporating bone tissue engineering. In this present work, three types of biomimetic heterogeneous porous scaffolds (HPS) were designed with the help of the Voronoi tessellation method and Swarm Intelligence and those were analysed under fluid perfusion as well as under static loading conditions. In computational fluid dynamics (CFD) analysis, the wall shear stress (WSS) and the permeability of the porous scaffolds were compared to the natural trabecular bone to understand their hydrodynamic responses. In static analysis, the von Mises stresses of the Ti6Al4V scaffolds were checked to ensure no-yield condition. The strain energy density (SED) distributions were also studied on the neighbouring bone region of the femur greater trochanter to obtain stress shielding (SS) patterns and these findings were then compared with the natural trabecular bone at the same anatomical region. The outcome parameters, viz. the induced WSS, von Mises stress, the permeability, and SS of the scaffold, are found to be independent of the scaffold architecture. The von Mises stress and permeability increased with an increase in porosities, while the induced WSS and SS nature of the scaffolds showed the reverse trend. The results showed that the HPS designed based on the Swarm Intelligence incorporating Physarum Polycephalum algorithm offered the least SS level of 41.096 for 75% porous HPS, which may be considered the most promising result. Considering all the parameters, the novel designed scaffold based on Swarm Intelligence showed the most trabecular bone mimicking nature compared to the other scaffolds. [ABSTRACT FROM AUTHOR]

Electrospinning is an effective method to fabricate fibrous scaffolds that mimic the ECM of bone tissue on a nano- to macro-scale. However, a limitation of electrospun fibrous scaffolds for bone tissue engineering is the structure formed by densely compacted fibers, which significantly impedes cell infiltration and tissue ingrowth. To address this problem, several researchers have developed numerous techniques for fabricating 3D fibrous scaffolds with customized topography and pore size. Despite the success in developing various 3D electrospun scaffolds based on fiber repulsion, the lack of contact points between fibers in those scaffolds has been shown to hinder cell attachment, migration, proliferation, and differentiation due to excessive movement of the fibers. In this article, we introduce a Dianthus caryophyllus-inspired scaffold fabricated using SIAC-PE, a modified collector under specific viscosity conditions of PCL/LA solution. The developed scaffold mimicking the structural similarities of the nature-inspired design presented enhanced cell proliferation, infiltration, and increased expression of bone-related factors by reducing fiber movements, presenting high space interconnection, high porosity, and controlled fiber topography. [ABSTRACT FROM AUTHOR]

Physical factors in the cellular microenvironment have critical effects on stem cell differentiation. The utilization of physical factors to promote the osteogenic differentiation of stem cells has been established as a new strategy for developing bone tissue engineering scaffolds. In this context, scaffolds with multiscale anisotropy are considered to possess biomimetic properties, which are advantageous for their biological performance. In the present study, a novel magnetic anisotropic hydrogel (MAH) with magnetic and topographic anisotropy was designed by combining static magnetic field-induced magnetic nanomaterials and a hydrogel. In in vitro studies, the MAH exhibited excellent biocompatibility and osteogenic bioactivity. The alkaline phosphatase activity and the expression of osteogenic-related genes and proteins induced by the MAH were greater than those induced by the pure PEGDA–GelMA hydrogel (PGH) and the magnetic isotropic hydrogel (MIH). In addition, the present study revealed that the dual anisotropic properties of the MAH activated the NOTCH1/2 pathway by upregulating SNHG5 and downstream SIRT6, which modulates the level of NOTCH1/2 by antagonizing DNMT1 protein stability, ultimately inducing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Furthermore, the MAH, MIH, and PGH were tested for in vivo bone regeneration in rabbits with femur defects, and the results demonstrated that the MAH effectively stimulated bone regeneration. Taken together, these findings suggest that this magnetically and topographically anisotropic biomimetic hydrogel might be a promising candidate for application in the field of bone tissue regeneration. A novel magnetic anisotropic hydrogel (MAH) with magnetic and topographic anisotropy was designed by combining static magnetic field-induced magnetic nanomaterials and a hydrogel. The duel anisotropic hydrogel promotes osteogenic differentiation of BMSCs through upregulating SNHG5 and downstream SIRT6, which modulated the level of NOTCH1/2 by antagonizing DNMT1 protein stability. [ABSTRACT FROM AUTHOR]

Bacterial cellulose (BC) is a biomaterial extensively studied in tissue engineering due to its favorable properties. Porosity, biocompatibility, biodegradability and mechanical durability are essential material properties for scaffold use in tissue engineering. This study aims to fabricate porous scaffolds using a moldable and degradable BC-HAp composite for bone tissue engineering. BC was produced by Komagataeibacter sucrofermentans under static culture conditions. The harvested BC membranes were purified and then mechanically shredded. BC oxidation was performed using different sodium periodate concentrations (0.05–0.5 M) and treatment times (0.5–12 h). Oxidized BCs (oxBC) were modified with hydroxyapatite (HAp), then were moulded, lyophilized, and characterized. The degradability of the scaffolds was determined for 45 days. Cytotoxic analysis of oxBC scaffolds was carried out for 7 days using the L929 fibroblast cell line. The oxidation degrees of the shredded BC samples were between 6.75 and 81%, which increased in line with the increasing concentration and application time of periodate. The scaffolds prepared using oxidized cellulose for 30 and 60 min (oxBC30 and oxBC60) preserved their integrity, These scaffolds showed a weight loss of 9% and 14% in 45 days, respectively. The pore distribution was between 50 and 450 µm and concentrated in the 50–150 µm range. The compression moduli were 88.72 kPa and 138.88 kPa for oxBC30-HAp and oxBC60-HAp, respectively. It was determined that oxBC did not show a significant difference in cell viability compared to the control groups and was not cytotoxic. In conclusion, degradable and more porous bone scaffolds were fabricated using mouldable oxBC. [ABSTRACT FROM AUTHOR]

Cyanophycin (CGP) is a polypeptide consisting of amino acids—aspartic acid in the backbone and arginine in the side chain. Owing to its resemblance to cell adhesive motifs in the body, it can be considered suitable for use in biomedical applications as a novel component to facilitate cell attachment and tissue regeneration. Although it has vast potential applications, starting with nutrition, through drug delivery and tissue engineering to the production of value-added chemicals and biomaterials, CGP has not been brought to the industry yet. To develop scaffolds using CGP powder produced by bacteria, its properties (e.g., biocompatibility, morphology, biodegradability, and mechanical strength) should be tailored in terms of the requirements of the targeted tissue. Crosslinking commonly stands for a primary modification method for renovating biomaterial features to these extents. Herein, we aimed to crosslink CGP for the first time and present a comparative study of different methods of CGP crosslinking including chemical, physical, and enzymatic methods by utilizing glutaraldehyde (GTA), UV exposure, genipin, 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS), and monoamine oxidase (MAO). Crosslinking efficacy varied among the samples crosslinked via the different crosslinking methods. All crosslinked CGP were non-cytotoxic to L929 cells, except for the groups with higher GTA concentrations. We conclude that CGP is a promising candidate for scaffolding purposes to be used as part of a composite with other biomaterials to maintain the integrity of scaffolds. The initiative study demonstrated the unknown characteristics of crosslinked CGP, even though its feasibility for biomedical applications should be confirmed by further examinations. Key points: • Cyanophycin was crosslinked by 5 different methods • Crosslinked cyanophycin is non-cytotoxic to L929 cells • Crosslinked cyanophycin is a promising new material for scaffolding purposes [ABSTRACT FROM AUTHOR]