Search Results (33)

Organoids and microphysiological systems (MPSs) have emerged as physiologically relevant platforms that recapitulate key structural and functional features of human organs, tissues, and microenvironments. As one of the essential components that define the success of these systems, hydrogels play the central role of providing a three-dimensional, biomimetic scaffold that supports cell viability, spatial organization, and dynamic signaling. Natural polymer-based hydrogels, derived from materials such as collagen, gelatin, hyaluronic acid, and alginate, offer favorable properties including biocompatibility, degradability, and an extracellular matrix-like architecture. This review presents recent advances in the design and application of such hydrogels, focusing on crosslinking strategies (physical, chemical, and hybrid), the viscoelastic characteristics, and stimuli-responsive behaviors. The influence of these materials on cellular processes, such as stemness maintenance, differentiation, and morphogenesis, is critically examined. Furthermore, the applications of organoid culture and dynamic MPS platforms are discussed, highlighting their roles in morphogen delivery, barrier formation, and vascularization. Current challenges and future perspectives toward achieving standardized, scalable, and translational hydrogel systems are also addressed. Full article

Tracheal reconstruction remains a formidable clinical challenge, particularly for long-segment defects that are not amenable to standard surgical resection or primary anastomosis. Tissue engineering has emerged as a promising strategy for restoring the tracheal structure and function through the integration of biomaterials, stem cells, and bioactive molecules. This review provides a comprehensive overview of recent advances in tissue-engineered tracheal grafts, particularly in scaffold design, cellular sources, fabrication technologies, and early clinical experience. Innovations in biomaterial science, three-dimensional printing, and scaffold-free fabrication approaches have broadened the prospects for patient-specific airway reconstruction. However, persistent challenges, including incomplete epithelial regeneration and mechanical instability, have hindered its clinical translation. Future efforts should focus on the design of modular biomimetic scaffolds, the enhancement of immunomodulatory strategies, and preclinical validation using robust large animal models. Sustained interdisciplinary collaboration among surgical, engineering, and biological fields is crucial for advancing tissue-engineered tracheal grafts for routine clinical applications. Within this context, biomimetic approaches, including three-dimensional bioprinting, hybrid materials, and scaffold-free constructs, are gaining prominence as strategies to replicate the trachea’s native architecture and improve graft integration. Full article

Bioactive materials have recently shown potential in nerve repair and regeneration by promoting the growth of new cells, tissue repair, and restoring nerve function. These natural, synthetic, and hybrid materials offer a biomimetic structure, enhance cell attachment, and release bioactive molecules that promote the axonal extension of severed nerves. Scaffold-based preclinical studies have shown promising results on enhancing nerve repair; however, they are limited by the immune response and fabrication, scalability, and cost. Nevertheless, advances in manufacturing, including 3D bioprinting, and other strategies, such as gene editing by CRISPR, will overcome these shortcomings. The opportunity for the development of individualized approaches and specific treatment plans for each patient will also increase the effectiveness of bioactive materials for the treatment of nerve injuries. Combining bioactive materials with the neural interface can develop new reliable therapeutic solutions, particularly for neuroprosthetics. Finally, it is essential to stress a multidisciplinary focus, and future studies are needed to enhance the potential of bioactive materials for patients with nerve injuries and the field of regenerative medicine. Full article

The long-term success of bone implant scaffolds depends on numerous factors, such as their porosity, mechanical properties, and biocompatibility. These properties depend on the type of material, such as metals and their alloys or ceramics, and the procedure used to create the scaffolds. This study aims to find the biomimetic properties of aluminum 6061 (Al 6061) alloy through Digital Light Processing (DLP) and sintering. Hollow cylindrical Al 6061 samples are printed through the DLP process at 90, 110, and 130 Wt.% aluminum powder concentrations inside a photocurable resin. The ideal temperature at which the material is sintered is 550 °C for 130 and 110 Wt.% and 530 °C for 90 Wt.%. The overall pore size ranges in the Al 6061 of these three concentrations from 30 μm to 700 μm. The compression test revealed the materials’ Ultimate Tensile Strengths (UTSs) to be 1.72, 2.2, and 1.78 MPa for the 90, 110, and 130 Wt.% materials, respectively. A simulation of the Al 6061 material as linear isotropic resulted in the UTS being 2.2 MPa. This novel hybrid of the additive manufacturing method and sintering created a scaffold model with anisotropic properties closer to trabecular bone, which could be used to observe fracture progression and could be tested for implant capabilities. Full article

Wound healing is important for skin after deep injuries or burns, which can lead to hospitalization, long-term morbidity, and mortality. In this field, tissue-engineered skin substitutes have therapy potential to assist in the treatment of acute and chronic skin wounds, where many requirements are still unmet. Hence, in this study, a novel type of biocompatible ternary polymer hybrid hydrogel scaffold was designed and produced through an entirely eco-friendly aqueous process composed of carboxymethyl cellulose, chitosan, and polyvinyl alcohol and chemically cross-linked by citric acid, forming three-dimensional (3D) matrices, which were biofunctionalized with L-arginine (L-Arg) to enhance cellular adhesion. They were applied as bilayer skin biomimetic substitutes based on human-derived cell cultures of fibroblasts and keratinocytes were seeded and grown into their 3D porous structures, producing cell-based bio-responsive hybrid hydrogel scaffolds to assist the wound healing process. The results demonstrated that hydrophilic hybrid cross-linked networks were formed via esterification reactions with the 3D porous microarchitecture promoted by foam templating and freeze-drying. These hybrids presented chemical stability, physicochemical properties, high moisture adsorption capacity, surface properties, and a highly interconnected 3D porous structure well suited for use as a skin substitute in wound healing. Additionally, the surface biofunctionalization of these 3D hydrogel scaffolds with L-arginine through amide bonds had significantly enhanced cellular attachment and proliferation of fibroblast and keratinocyte cultures. Hence, the in vivo results using Hairless mouse models (an immunocompromised strain) confirmed that these responsive bio-hybrid hydrogel scaffolds possess hemocompatibility, bioadhesion, biocompatibility, adhesiveness, biodegradability, and non-inflammatory behavior and are capable of assisting the skin wound healing process. Full article

Bone has the ability to heal itself; however, bone defects fail to heal once the damage exceeds a critical size. Bone regeneration remains a significant clinical challenge, with autograft considered the ideal bone graft material due to its sufficient porosity, osteogenic cells, and biological growth factors. However, limitations to bone grafting, such as limited bone stock and high resorption rates, have led to a great deal of research into developing bone graft substitutes. The P28 peptide is a small molecule bioactive biomimetic alternative to mimic the bone morphogenetic protein 2 (BMP-2). In this study, we investigated the potential of P28-loaded hybrid scaffolds to mimic the natural bone structure for enhancing the bone regeneration process. We hypothesized that the peptide-loaded scaffolds and nude scaffolds both have the potential to promote bone healing, and the bone healing process is accelerated by the release of the peptide. To verify our hypothesis, C2C12 cells were evaluated for the presence of calcium deposits by histological stain at 7 and 14 days in cultures with hybrid scaffolds. Total RNA was isolated from C2C12 cells cultured with hybrid scaffolds for 7 and 14 days to assess osteoblast differentiation. The project findings demonstrated that the hybrid scaffold could enhance osteoblast differentiation and significantly improve the therapeutic effects of the scaffold in bone regeneration. Full article

The process of bone regeneration is complicated, and it is still a major clinical challenge to regenerate critical-size bone defects caused by severe trauma, infection, and tumor resection. Intracellular metabolism has been found to play an important role in the cell fate decision of skeletal progenitor cells. GW9508, a potent agonist of the free fatty acid receptors GPR40 and GPR120, appears to have a dual effect of inhibiting osteoclastogenesis and promoting osteogenesis by regulating intracellular metabolism. Hence, in this study, GW9508 was loaded on a scaffold based on biomimetic construction principles to facilitate the bone regeneration process. Through 3D printing and ion crosslinking, hybrid inorganic-organic implantation scaffolds were obtained after integrating 3D-printed β-TCP/CaSiO₃ scaffolds with a Col/Alg/HA hydrogel. The 3D-printed β-TCP/CaSiO₃ scaffolds had an interconnected porous structure that simulated the porous structure and mineral microenvironment of bone, and the hydrogel network shared similar physicochemical properties with the extracellular matrix. The final osteogenic complex was obtained after GW9508 was loaded into the hybrid inorganic-organic scaffold. To investigate the biological effects of the obtained osteogenic complex, in vitro studies and a rat cranial critical-size bone defect model were utilized. Metabolomics analysis was conducted to explore the preliminary mechanism. The results showed that 50 μM GW9508 facilitated osteogenic differentiation by upregulating osteogenic genes, including Alp, Runx2, Osterix, and Spp1 in vitro. The GW9508-loaded osteogenic complex enhanced osteogenic protein secretion and facilitated new bone formation in vivo. Finally, the results from metabolomics analysis suggested that GW9508 promoted stem cell differentiation and bone formation through multiple intracellular metabolism pathways, including purine and pyrimidine metabolism, amino acid metabolism, glutathione metabolism, and taurine and hypotaurine metabolism. This study provides a new approach to address the challenge of critical-size bone defects. Full article

The high incidence of osteochondral defects has increased the interest in the development of improved repairing alternatives, with tissue engineering being considered a promising approach. The hierarchical, complex structure of osteochondral tissue requires the design of a biomimetic multilayered scaffold. Here, a multilayered and multiphasic 3D macroporous structure was achieved at subzero temperature by the Michael addition reaction of amino functionalities of collagen with acryloyl groups of a bifunctionalized poly(ε-caprolactone). This green approach has been successfully applied to crosslink layers of different composition, both for their efficient sequential formation and connection. Polyethylenimine functionalized nano-hydroxyapatite (nHAp_LPEI) was added to the bottom layer. The resulting hybrid cryogels were characterized by morphology, equilibrium swelling ratios, compressive strength analysis, and MTS assay. They presented good stability, integrity, and biocompatibility. The results revealed that the properties of the prepared constructs may be tuned by varying the composition, number, and thickness of the layers. The Young modulus values were between 3.5 ± 0.02 and 10.5 ± 0.6 kPa for the component layers, while for the multilayered structures they were more than 7.3 ± 0.2 kPa. The equilibrium swelling ratio varied between 4.6 and 14.2, with a value of ~10.5 for the trilayered structure, correlated with the mean pore sizes (74–230 µm). Full article

In tissue engineering, the potential of re-growing new tissue has been considered, however, developments towards such clinical and commercial outcomes have been modest. One of the most important elements here is the selection of a biomaterial that serves as a “scaffold” for the regeneration process. Herein, we designed hydrogels composed of two biocompatible natural polymers, namely gelatin with photopolymerizable functionalities and a pectin derivative amenable to direct protein conjugation. Aiming to design biomimetic hydrogels for bone regeneration, this study proposes double-reinforcement by way of inorganic/biopolymer hybrid filling composed of Si-based compounds and cellulose nanofibers. To attain networks with high flexibility and elastic modulus, a double-crosslinking strategy was envisioned—photochemical and enzyme-mediated conjugation reactions. The dual cross-linked procedure will generate intra- and intermolecular interactions between the protein and polysaccharide and might be a resourceful strategy to develop innovative scaffolding materials. Full article

Hybrid organic-inorganic (dendritic polymer-silica) xerogels containing silver nanoparticles (Ag Nps) were developed as antibacterial leather coatings. The preparation method is environmentally friendly and is based on two biomimetic reactions. Silica gelation and spontaneous Ag Nps formation were both mediated by hyperbranched poly (ethylene imine) (PEI) scaffolds of variable Mw (2000–750,000). The formation of precursor hydrogels was monitored by dynamic light scattering (DLS). The chemical composition of the xerogels was assessed by infrared spectroscopy (IR) and energy-dispersive X-ray spectroscopy (EDS), while the uniformity of the coatings was established by scanning electron microscopy (SEM). The release properties of coated leather samples and their overall behavior in water in comparison to untreated analogs were investigated by Ultraviolet-Visible (UV-Vis) spectroscopy. Antibacterial activity was tested against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and antibiofilm properties against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Acinetobacter baumannii, and Enterococcus faecalis, while the SARS-CoV-2 clinical isolate was employed for the first estimation of their antiviral potential. Toxicity was evaluated using the Jurkat E6.1 cell line. Finally, water-contact angle measurements were implemented to determine the enhancement of the leather surface hydrophilicity caused by these composite layers. The final advanced products are intended for use in medical applications. Full article

To treat critical-size bone defects, composite materials and tissue-engineered bone grafts play important roles in bone repair materials. The purpose of this study was to investigate the bone regenerative potential of hybrid scaffolds consisting of macroporous calcium phosphate cement (CPC) and microporous mineralized collagen matrix (MCM). Hybrid scaffolds were synthetized by 3D plotting CPC and then filling with MCM (MCM-CPC group) and implanted into a 5 mm critical size femoral defect in rats. Defects left empty (control group) as well as defects treated with scaffolds made of CPC only (CPC group) and MCM only (MCM group) served as controls. Eight weeks after surgery, micro-computed tomography scans and histological analysis were performed to analyze the newly formed bone, the degree of defect healing and the activity of osteoclasts. Mechanical stability was tested by 3-point-bending of the explanted femora. Compared with the other groups, more newly formed bone was found within MCM-CPC scaffolds. The new bone tissue had a clamp-like structure which was fully connected to the hybrid scaffolds and thereby enhanced the biomechanical strength. Together, the biomimetic hybrid MCM-CPC scaffolds enhanced bone defect healing by improved osseointegration and their differentiated degradation provides spatial effects in the process of critical-bone defect healing. Full article

In recent years, tissue engineering has achieved significant advancements towards the repair of damaged tissues. Until this day, the vascularization of engineered tissues remains a challenge to the development of large-scale artificial tissue. Recent breakthroughs in biomaterials and three-dimensional (3D) printing have made it possible to manipulate two or more biomaterials with complementary mechanical and/or biological properties to create hybrid scaffolds that imitate natural tissues. Hydrogels have become essential biomaterials due to their tissue-like physical properties and their ability to include living cells and/or biological molecules. Furthermore, 3D printing, such as dispensing-based bioprinting, has progressed to the point where it can now be utilized to construct hybrid scaffolds with intricate structures. Current bioprinting approaches are still challenged by the need for the necessary biomimetic nano-resolution in combination with bioactive spatiotemporal signals. Moreover, the intricacies of multi-material bioprinting and hydrogel synthesis also pose a challenge to the construction of hybrid scaffolds. This manuscript presents a brief review of scaffold bioprinting to create vascularized tissues, covering the key features of vascular systems, scaffold-based bioprinting methods, and the materials and cell sources used. We will also present examples and discuss current limitations and potential future directions of the technology. Full article

The use of biomaterials and scaffolds to boost bone regeneration is increasingly gaining interest as a complementary method to the standard surgical and pharmacological treatments in case of severe injuries and pathological conditions. In this frame, the selection of biomaterials and the accurate assessment of the manufacturing procedures are considered key factors in the design of constructs able to resemble the features of the native tissue and effectively induce specific cell responses. Accordingly, composite scaffolds based on type-I-collagen can mimic the composition of bone extracellular matrix (ECM), while electrospinning technologies can be exploited to produce nanofibrous matrices to resemble its architectural organization. However, the combination of collagen and electrospinning reported several complications due to the frequent denaturation of the protein and the variability of results according to collagen origin, concentration, and solvent. In this context, the strategies optimized in this study enabled the preparation of collagen-based electrospun scaffolds characterized by about 100 nm fibers, preserving the physico-chemical properties of the protein thanks to the use of an acetic acid-based solvent. Moreover, nanoparticles of mesoporous bioactive glasses were combined with the optimized collagen formulation, proving the successful design of composite scaffolds resembling the morphological features of bone ECM at the nanoscale. Full article

Promising strategies for cartilage regeneration rely on the encapsulation of mesenchymal stromal cells (MSCs) in a hydrogel followed by an injection into the injured joint. Preclinical and clinical data using MSCs embedded in a collagen gel have demonstrated improvements in patients with focal lesions and osteoarthritis. However, an improvement is often observed in the short or medium term due to the loss of the chondrocyte capacity to produce the correct extracellular matrix and to respond to mechanical stimulation. Developing novel biomimetic materials with better chondroconductive and mechanical properties is still a challenge for cartilage engineering. Herein, we have designed a biomimetic chemical hydrogel based on silylated collagen-mimetic synthetic peptides having the ability to encapsulate MSCs using a biorthogonal sol-gel cross-linking reaction. By tuning the hydrogel composition using both mono- and bi-functional peptides, we succeeded in improving its mechanical properties, yielding a more elastic scaffold and achieving the survival of embedded MSCs for 21 days as well as the up-regulation of chondrocyte markers. This biomimetic long-standing hybrid hydrogel is of interest as a synthetic and modular scaffold for cartilage tissue engineering. Full article

The meniscus has poor intrinsic regenerative capability, and its injury inevitably leads to articular cartilage degeneration. Although there are commercialized off-the-shelf alternatives to achieve total meniscus regeneration, each has its own shortcomings such as individualized size matching issues and inappropriate mechanical properties. We manufactured a polycaprolactone-based patient-specific designed framework via a Computed Tomography scan images and 3D-printing technique. Then, we completed the hybrid-scaffold by combining the 3D-printed framework and mixture micro-size composite which consists of polycaprolactone and sodium chloride to create a cell-friendly microenvironment. Based on this hybrid-scaffold with an autograft cell source (fibrochondrocyte), we assessed mechanical and histological results using the rabbit total meniscectomy model. At postoperative 12-week, hybrid-scaffold achieved neo-meniscus tissue formation, and its shape was maintained without rupture or break away from the knee joint. Histological and immunohistochemical analysis results showed obvious ingrowth of the fibroblast-like cells and chondrocyte cells as well as mature lacunae that were embedded in the extracellular matrix. Hybrid-scaffolding resulted in superior shape matching as compared to original meniscus tissue. Histological analysis showed evidence of extensive neo-meniscus cell ingrowth. Additionally, the hybrid-scaffold did not induce osteoarthritis on the femoral condyle surface. The 3D-printed hybrid-scaffold may provide a promising approach that can be applied to those who received total meniscal resection, using patient-specific design and autogenous cell source. Full article