Search Results (401)

Human skin remains difficult to model in vitro because it brings together stratified epidermal, dermal, hypodermal, vascular, immune, appendageal, neural, and microbial elements within a single tissue. Traditional two-dimensional cultures and animal models still offer useful insight, but both have clear translational limits. Three-dimensional (3D) human skin models have therefore become increasingly valuable for mechanistic, pharmacologic, and regenerative research. This narrative review followed a fit-for-purpose literature selection framework. Priority was given to primary studies and reviews published between 2019 and 2025 that reported major advances in model architecture, biomaterials, vascularization, immune integration, appendage formation, sensorization, or translational application. Greater weight was given to studies that linked added complexity to measurable functional outputs. Current platforms include organotypic human skin equivalents, bioprinted constructs, microfluidic skin-on-a-chip systems, and pluripotent stem cell-derived organoids. Important advances include self-assembled or decellularized matrices that more closely reflect native extracellular matrix composition, perfusable microvasculature, hypodermal incorporation, immune cell integration, and real time sensing. These systems now support work in barrier testing, safety testing, dermal drug development, inflammatory dermatoses, melanoma, wound healing, aging, and regenerative transplantation. No single platform fully reproduces native human skin. The more relevant question is not how much complexity can be added, but which added features meaningfully improve performance for a defined endpoint. A fit-for-purpose framework may offer a better basis for model selection, benchmarking, standardization, and translational adoption. Future progress will depend on application specific validation, clearer performance benchmarks, scalable manufacturing, and closer alignment with regulatory and clinical needs. From that perspective, 3D skin models are best understood as complementary platforms for translational dermatology research. Full article

Background: Congenital pulmonary airway malformation (CPAM) is a rare developmental disorder characterized by cystic lung lesions, yet its extracellular matrix (ECM) composition remains poorly understood. This study employed decellularization and data-independent acquisition (DIA) proteomics to compare ECM profiles between cystic (CPAM) and histologically normal non-diseased (ND) regions from the lungs of four patients. Results: The decellularized scaffolds retained their native architecture with minimal residual DNA (<50 ng/mg). Proteomic analysis revealed 431 differentially expressed proteins (DEPs), with 171 upregulated and 260 downregulated in CPAM. Key findings revealed CPAM-specific enrichment of collagens (COL4A6, COL4A2, COL10A1, COL21A1 and PIIINP), glycoproteins (SPP1, FRAS1, FREM1, FREM2, LTBP1 and FBLN7), ECM regulators (TENM2, ROR2 and OMD), and ECM-affiliated proteins (ANXA7), alongside downregulation of glycoproteins (VASN and ABI3BP), proteoglycans (PODN and MXRA7), ECM regulators (SCARA5, PAPPA, SAA4, CPXM1, CTSC, THY1, SERPINA6/A1/D1, BSG, LYVE1, ITIH4 and CD44), and ECM-affiliated proteins (LGALSL). Pathway analysis highlighted the dysregulation of TGF-β, PI3K–AKT, and mTOR signaling in CPAM and aberrant ECM–cell interactions in pathogenesis. We also evaluated their functional properties and investigated the impact of ECM-based hydrogels on recellularization. Conclusions: These findings provide a comprehensive proteomic atlas of CPAM ECM alterations, offering insights into disease mechanisms and potential therapeutic targets. Full article

Background: The human amniotic membrane (hAM) is widely used in tissue engineering due to its low immunogenicity and extracellular matrix (ECM) rich in structural proteins; in this context, decellularization aims to remove cellular components while preserving tissue integrity, and this study aimed to compare the effects of two enzymatic methods (trypsin and thermolysin). Methods: Human amniotic membranes obtained from placentas were divided into three groups: non-decellularized control, trypsin-treated, and thermolysin-treated. The membranes were treated with 0.25 trypsin-EDTA for 60 min at 37 °C, followed by incubation with Triton X-100 for 30 min at 37 °C, or with 125 µg/mL thermolysin for 9 min at 37 °C. Histological analysis with hematoxylin–eosin and semi-quantitative scoring assessed epithelial and stromal integrity, immunohistochemistry evaluated laminin α and fibronectin expression with quantitative image analysis, and uniaxial tensile testing measured mechanical properties; no preregistration numbers or animal models were reported. Results: Trypsin achieved more effective epithelial removal, whereas thermolysin caused greater stromal disruption; no statistically significant differences in laminin α or fibronectin expression were found among groups (p > 0.05), indicating preservation of key ECM components; both treatments reduced mechanical performance, with thermolysin decreasing early- and mid-path stiffness and trypsin reducing late-path stress and work density. Conclusion: Both enzymatic protocols preserved ECM composition but induced distinct structural and mechanical alterations, suggesting that method selection should balance efficient cell removal with preservation of structural and functional properties according to the intended application. Full article

Objectives: Critical-sized bone defects continue to represent a substantial challenge in orthopedic clinical practice. Decellularized bone matrix (DBM) possesses favorable osteoconductive properties due to its retention of native extracellular matrix architecture and collagen components. However, its limited osteogenic bioactivity restricts its application in complex bone defect repair. This study aimed to construct a dendritic mesoporous silica (DMSN)-modified DBM composite scaffold loaded with teriparatide (DBM-DMSN@TPTD) and to systematically evaluate its physicochemical properties, drug release behavior, biocompatibility, and osteogenic differentiation-promoting capacity. Methods: A DBM scaffold was prepared from bovine femoral cancellous bone via a combined freeze–thaw and chemical detergent decellularization method. DMSNs were synthesized through a sol–gel method, amine-functionalized with APTES, and covalently grafted onto the DBM surface via EDC/NHS crosslinking. Teriparatide was loaded onto the composite scaffolds at three concentrations (1, 10, and 100 nmol/L). The scaffolds were characterized via SEM, TEM, BET, EDS and XPS. Decellularization efficacy was assessed by DAPI staining and nucleic acid quantification. Drug release behavior was evaluated through in vitro release studies, while biocompatibility and osteogenic differentiation of rat BMSCs were examined using Live/Dead staining, phalloidin/DAPI cytoskeletal staining, CCK-8 assays, ALP staining, and RUNX2/OCN immunofluorescence. Results: DMSNs demonstrated a dendritic mesoporous architecture, featuring a specific surface area of 390.44 ± 1.78 m²/g and pore diameters within the range of 15–20 nm. DBM showed effective removal of immunogenicity, with well-preserved collagen architecture. Drug release displayed a biphasic pattern, with 56.03% released within the first 72 h and 83.23% by day 16. None of the tested scaffolds showed obvious cytotoxicity under the experimental conditions. The DBM-DMSN@TPTD-M group (10 nmol/L) produced the strongest effects on BMSC proliferation and osteogenic differentiation, as indicated by the highest ALP activity and elevated RUNX2 and OCN expression (p < 0.05). Conclusions: The DBM-DMSN@TPTD scaffold offers a native bone microenvironment, sustained drug release, and osteogenic activity in vitro. These features may support BMSC proliferation and osteogenic differentiation. Accordingly, this scaffold warrants further investigation as a potential strategy for bone defect repair. Full article

In vitro neurovascular unit (NVU) models are essential for reproducing blood–brain barrier (BBB) transport and neurovascular cell interactions. However, the literature remains fragmented: biomaterial chemistry, fabrication parameters and organ-on-a-chip architecture are commonly evaluated in isolation, while inconsistent reporting of matrix properties, processing history, cell source, flow and barrier readouts prevents head-to-head comparison and the extraction of transferable design rules. To address this gap, this review integrates biomaterials, manufacturing technologies and organ-on-a-chip engineering within a unified material–process–structure–function framework. We translate endothelial junctions, basement-membrane components and perivascular cells into experimentally actionable material requirements; compare natural, synthetic, semisynthetic and decellularized extracellular-matrix hydrogels; and examine crosslinking, peptide functionalization, stimuli responsiveness, composite-network formation and preparation methods. Findings from Transwell, microfluidic, tubular, self-assembled and 3D-bioprinted BBB systems are used to relate matrix stiffness, degradability, ligand density, permeability, device-body material and fabrication route to barrier maturation, analytical access and reproducibility. By defining matched controls and minimum reporting requirements for chemistry, mechanics, transport and processing, this review provides a practical basis for next-generation BBB models that can improve permeability and efficacy screening in drug discovery, reproduce disease- and patient-specific barrier dysfunction, and support individualized response testing with iPSC- or patient-derived cells. Full article

The persistent shortage of donor organs and the inherent drawbacks of autologous grafts highlight the urgent need for advanced biomaterial scaffolds in regenerative medicine. Synthetic polymers and animal-derived matrices offer structural support, yet they frequently lack the biological complexity of native tissue or carry translational liabilities—xenogeneic antigens, pathogen transmission risk, and batch variability. This review positions the human placenta as a compelling, ethically sourced, and abundant reservoir for fully human, xeno-free biomaterials. We examine the placenta’s distinct anatomical compartments and their rich complement of extracellular matrix (ECM) proteins, growth factors, and bioactive cytokines. These components confer potent pro-angiogenic, anti-inflammatory, antimicrobial, and immunomodulatory properties, enabling precise direction of cellular behavior and tissue regeneration. We systematically assess recent advances in decellularization and the processing strategies required to preserve these bioactivities while eliminating immunogenic material. By integrating current tissue engineering applications with the regulatory and ethical frameworks shaping clinical translation, we argue that placenta-derived matrices are uniquely positioned to transcend the limitations of conventional scaffolds and serve as a robust platform for future regenerative therapies. Full article

The temporomandibular joint (TMJ) is a highly specialized synovial joint responsible for essential functions such as mastication, speech, and swallowing. Owing to its unique anatomical organization, complex biomechanics, and heterogeneous tissue composition, regeneration of the TMJ remains one of the greatest challenges in craniofacial reconstructive surgery. Conventional treatment modalities, including autologous grafts, alloplastic prostheses, and total joint replacement, are associated with several limitations, including donor-site morbidity, prosthetic wear, limited biological integration, and the inability to restore native tissue architecture. Three-dimensional (3D) bioprinting has emerged as a promising regenerative strategy capable of fabricating patient-specific living constructs that closely mimic the structural and functional characteristics of the native joint. This review summarizes recent advances in TMJ bioprinting, with particular emphasis on the regeneration of the mandibular condylar fibrocartilage, subchondral bone, articular disc, and integrated osteochondral constructs. The literature search covered publications from January 2010 through March 2026, and it was conducted using major scientific databases, including PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Current progress in cellular sources, including mesenchymal stem cells and induced pluripotent stem cells, biomaterials and bioinks, growth factor delivery, and multimaterial bioprinting technologies is discussed. Particular attention is given to the challenges associated with reproducing the complex osteochondral interface, achieving adequate vascularization, ensuring long-term mechanical stability, and directing tissue-specific cell differentiation. Emerging technologies, including four-dimensional (4D) bioprinting, decellularized extracellular matrix-based bioinks, artificial intelligence-assisted design, patient-specific computational modeling, and bioreactor-mediated tissue maturation, are highlighted as promising approaches to improve construct functionality and clinical translation. Although the clinical application of TMJ bioprinting remains in its early stages, rapid advances in regenerative medicine and biofabrication technologies indicate that personalized bioengineered joint reconstruction may become a viable therapeutic option for the treatment of severe temporomandibular joint disorders in the future. Full article

Three-dimensional (3D) bioprinting has emerged as a versatile biofabrication strategy that enables the precise, spatiotemporally controlled co-deposition of living cells, biomaterials, and bioactive agents, including growth factors, cytokines, and extracellular matrix (ECM) components, into geometrically defined 3D constructs. By translating digital design models derived from computed tomography (CT), magnetic resonance imaging (MRI), or computational modeling directly into physical tissue architectures, 3D bioprinting facilitates the assembly of hierarchically organized constructs that closely recapitulate the structural, mechanical, and functional characteristics of native tissues. The principal 3D bioprinting strategies are broadly classified into scaffold-based and scaffold-free approaches. Engineered bioinks, whether formulated as cell-laden natural, synthetic, or composite polymer hydrogels, tissue-derived decellularized ECM (dECM) components, or pure cellular spheroids and organoids, constitute the cornerstone of these biofabrication platforms. Scaffold-based 3D bioprinting comprises extrusion-based, droplet-based (inkjet and drop-on-demand), light-based vat photopolymerization (stereolithography and digital light processing), and laser-assisted bioprinting based on laser-induced forward transfer (LIFT). Each of these modalities imposes distinct constraints on bioink rheology, crosslinking mechanisms, spatial resolution, throughput, and post-printing cell viability; consequently, a specific 3D bioprinting strategy is selected according to the specific requirements of the target tissue application. Scaffold-free 3D bioprinting and bioassembly techniques, including the Kenzan method, aspiration-assisted bioprinting, magnetic bioprinting, and other field-directed tissue assembly approaches, enable the fabrication of spheroid- and organoid-based constructs without the necessity for exogenous biomaterial scaffolds. Because native tissues exhibit diversity in cellular composition, ECM architecture, mechanical properties, and physiological function, no individual bioprinting platform or bioink formulation serves as a universal 3D bioprinting solution. The engineering of biomimetic tissue constructs, therefore, requires the selection of application-tailored fabrication approaches. Under this biofabrication paradigm, 3D bioprinting has been applied across a wide range of tissue engineering targets, including skin, bone, cartilage, osteochondral interfaces, cardiac and vascular tissue, neural structures, ocular, dental, and adipose tissue. This review discusses recent advances in scaffold-based and scaffold-free 3D bioprinting applications for tissue engineering and regenerative medicine across diverse tissue systems. Full article

Decorin, a proteoglycan shown to inhibit transforming growth factor β1 (TGF-β1) signaling, has been increasingly considered as a potential anti-fibrotic agent to aid in therapies addressing corneal scarring and blindness. Decorin is also known to interact with a wide range of other growth factors, such as platelet-derived growth factor (PDGF), which has been shown to stimulate corneal cell migration to repopulate the decellularized region of the wounded cornea. In other tissues, decorin has been shown to inhibit PDGF-mediated migration and prolong wound healing. However, our understanding of the effect of decorin on PDGF signaling in the corneal stroma environment is limited. Specifically, thus far, there have been no studies investigating the interaction between decorin and PDGF in the context of the uniquely organized fibrillar collagen extracellular matrix (ECM), which provides topographic cues that guide cell migration during wound healing. The purpose of this study is to use an in vitro model of decorin-coated aligned collagen fibrils analogous to the corneal stroma ECM to investigate this interaction. With this in vitro model, we demonstrate that decorin inhibits the response of PDGF-BB-stimulated keratocytes to a 2-dimensional (2D) aligned collagen fibril ECM, reducing cell alignment, motility, PDGF receptor β (PDGFRβ) phosphorylation, and wound closure. We observed that when presented with a decellularized wound region, cells on the decorin-coated substrates migrated more randomly and were less aligned with the underlying aligned collagen fibrils than cells on uncoated fibrils, resulting in slower wound closure. Furthermore, PDGF-BB-stimulated cells on the decorin coating had increased branching and reduced solidity, representing a shift from the elongated, bipolar morphology typically resulting from PDGF-BB treatment towards the stellate, branched keratocyte phenotype. While decorin seems to be an effective agent against TGF-β1-mediated fibrosis, its interaction with PDGF-BB appears to present other challenges to wound healing that should be considered in the development of therapies for healthy corneal wound healing. Full article

Myocardial infarction remains a leading cause of heart failure owing to the limited regenerative capacity of adult cardiac tissue, underscoring the need for biomimetic therapeutic platforms that combine structural support with biological functionality. Accordingly, this study aimed to develop a multifunctional electrospun cardiac patch by integrating decellularized neonatal porcine myocardial extracellular matrix (dECM), gelatin, and microbiota-derived postbiotics for cardiac tissue engineering. The fabricated patches were comprehensively characterized in terms of their morphology, mechanical properties, biodegradation behavior, antibacterial activity, antioxidant capacity, and in vitro biocompatibility. Postbiotics derived from Lactiplantibacillus plantarum EIR/IF-1 exhibited potent antimicrobial activity against methicillin-resistant Staphylococcus aureus, strong antioxidant capacity, and significant anti-inflammatory activity through the suppression of pro-inflammatory mediators and upregulation of IL-10 expression. Moreover, they protected H9c2 cardiomyoblasts from oxidative stress, promoted COL1A1 expression, and supported ECM remodeling. The fabricated electrospun cardiac patches exhibited a homogeneous nanofibrous architecture, mechanically suitable properties (Young’s modulus ~4 MPa), controlled biodegradation over 7 days, favorable cell viability, and maintained the biological functionality of the incorporated postbiotics. Overall, the synergistic integration of tissue-specific dECM and microbiota-derived postbiotics yielded a multifunctional biohybrid cardiac patch with favorable structural and biological properties, supporting its potential as a promising platform for myocardial regeneration and next-generation cardiac tissue engineering. Full article

Background: Decellularized extracellular matrix (ECM) patches have emerged as a potential alternative to synthetic and autologous materials in pediatric cardiac surgery; however, clinical data on their use in septal defect repair remain limited. Methods: This single-center retrospective study evaluated the applicability and early outcomes of ECM scaffolds for pediatric septal defect repair using data from the national cardiac surgery registry. Early postoperative outcomes and perioperative variables were analyzed. Results: The study included 72 procedures performed in 68 patients (35 males and 33 females), aged 10 days to 16 years (median age: 187 days; IQR: 105–327 days). Reoperations accounted for 6% of cases. Postoperative complications occurred in 1.4% of patients, and continuous renal replacement therapy was required in 6 (8.8%) patients. Overall mortality was 2.9% (2/68 patients). No statistically significant differences were observed between atrial and ventricular septal defect groups. Conclusions: ECM patches appeared to be a safe and effective option for septal defect repair in pediatric cardiac surgery, demonstrating low complication rates and satisfactory early outcomes across different types of congenital heart defects. Full article

The meniscus is a fibrocartilaginous tissue essential for load transmission, shock absorption, joint stability, and cartilage protection in the knee. However, its intrinsic healing capacity is severely limited, particularly in the avascular region and in complex defects, often resulting in persistent symptoms, functional impairment, and progressive joint degeneration. Although current clinical interventions, including meniscal repair, partial meniscectomy, allograft transplantation, and scaffold-assisted meniscal substitution, can provide symptomatic and functional improvement in selected patients, durable structural and functional restoration remains difficult to achieve. Meniscus tissue engineering has therefore emerged as a potential strategy for tissue preservation and functional reconstruction. This review synthesizes recent advances in meniscus tissue-engineered scaffolds, focusing on biomaterial systems, biofabrication strategies, and translational progress. Natural polymers, decellularized extracellular matrix, synthetic polymers, and composite materials are discussed according to their respective roles in biological regulation, mechanical support, structural organization, and clinical feasibility. Emerging biofabrication strategies are further analyzed with respect to geometric reconstruction, zonal organization, fibrous anisotropy, and their implications for scaffold evaluation. Finally, current in vitro, preclinical, and clinical evidence is critically examined to identify the key barriers that still limit long-term regeneration and clinical translation. Full article

Acellular bone matrix, with its natural extracellular matrix components, has been considered a potential alternative platform for bone grafting. Our study focused on fabricating acellular bovine bone matrix (ABBM) and evaluating its in vitro characteristics and in vivo effect on bone repair. The bovine cancellous bone was subjected to ABBM preparation, which included partial demineralization and decellularization processing. The effects of the ABBM on human bone marrow-derived stem cells (hBMSCs) were evaluated, including viability, migration, attachment, and proliferation. A rabbit bone defect model was implanted with ABBM and histologically assessed for bone healing. The acellular properties were determined by the absence of nuclear material and the accepted minimum residual DNA content. An in vitro study indicated the ABBM’s positive effect on the migration of hBMSCs. ABBM was also demonstrated to support hBMSC attachment and proliferation. In vivo testing was performed in rabbits with a cranial bone defect, which showed complete bone healing after 8 weeks of grafting with ABBM. Overall, the fabricated ABBM demonstrated in vitro and in vivo biocompatibility and effective support for bone healing in vivo, and therefore represents a potential xenogeneic biomaterial for bone tissue repair. Full article

The rising prevalence of chronic kidney disease represents a major global health burden. Limitations of current renal replacement therapies, including donor organ shortages, rejection, and dialysis-related complications, underscore the need for innovative treatment options. This narrative review assesses the feasibility of bioengineered kidneys as an alternative to current treatments by discussing advances in decellularization, recellularization, and the transplantation of cell-on-scaffold kidneys. We propose that the development of functional bioengineered kidneys follows a hierarchical, staged process, in which vascular patency is the primary prerequisite for graft survival, followed by partial restoration of glomerular filtration, with complete tubular function remaining the final and most challenging milestone. Perfusion-based whole-organ decellularization has made significant progress in preserving the extracellular matrix, enabling the production of acellular human kidney scaffolds. However, complete recellularization of whole kidneys has not yet been achieved. Nevertheless, partially repopulated kidney scaffolds have been shown to withstand physiological blood pressure, produce urine, and exhibit filtration in large-animal models. Complete endothelial coverage of the vascular network proved essential for preventing thrombosis after transplantation. Current work on bioengineered kidneys shows promising results regarding feasibility for clinical application. It is important to note that most of the included studies are proof-of-concept, characterized by small sample sizes and short observation periods. Although these findings are crucial for further research, they cannot be generalized, and larger trials are recommended. In addition to cell-on-scaffold kidneys, 3D bioprinting is a promising technique that could eliminate the need for donor scaffolds. Full article

Current 3D tumor models for aggressive breast cancers inadequately recapitulate the native tumor microenvironment (TME), leading to poor translational potential. There is a critical need for models capable of mimicking the unique biochemical signals present in the TME. To address this gap, breast tissue and a patient-derived xenograft tumor were decellularized and processed to produce breast tissue- and tumor-specific decellularized extracellular matrices (dECM). Histology confirmed complete cellular removal while maintaining the ECM. Further, DNA content was significantly reduced while ECM composition (POSTN, COLI, FN1) was retained. Breast dECM was incorporated (0, 5, 10, 20, and 50 µg/mL) with triple-negative breast cancer cell lines to generate spheroids. Imaging and histology demonstrated that cells in low dECM (5 and 10 µg/mL) formed compact singular spheres, while higher dECM concentrations (20 and 50 µg/mL) resulted in cells concentrated on the outer edge of the sphere and irregular sphere circularity. RNA-sequencing of MDA-MB-231 dECM spheres demonstrated that gene changes were mediated by both the inclusion of dECM and its composition. High-density tumor dECM upregulated genes associated with metastasis, while high-density breast dECM enhanced tumor suppressors and anti-metastasis genes. These findings indicate that dECM provides physiological cues in 3D tumor models by incorporating TME. Full article