Journal of Tissue Engineering最新文献

Osteoporosis is a progressive skeletal disorder marked by an imbalance between bone resorption and formation, resulting in compromised microarchitecture and increased fracture risk. However, conventional pharmacological therapies have systemic side effects and limited targeting efficiency. Therefore, these limitations highlights the need for innovative strategies, and biomaterials have emerged as versatile tools, offering both structural support and the ability to modulate the osteoporotic bone microenvironment. This review outlines the key pathophysiological changes in osteoporosis including cellular dysregulation, ECM alteration, inflammation, and impaired vascularization underscoring the importance of restoring this niche for effective regeneration. A wide range of biomaterials, including natural/synthetic polymers, bioceramics, and metallic biomaterials and their alloys, are explored for their osteoconductive, osteoinductive, and mechanical features tailored to osteoporotic bone. This review also focuses on the functionalization approaches for the controlled delivery of drugs and growth factors (e.g. BMP-2, VEGF), and emerging gene/RNA therapies. The integration of biomaterials with stem cells and extracellular vesicles is discussed for enhancing osteogenesis, angiogenesis, and immunomodulation. Additionally, immuno-informed scaffold designs and bio-responsive materials responsive to pathological cues such as inflammation and oxidative stress are reviewed. Advanced technologies like three-dimensional printing and sensor-enabled scaffolds for real-time feedback are also addressed. Finally, the review considers translational barriers and highlights future directions combining material science, regenerative medicine, and personalized therapy for osteoporotic bone repair.

Chronic wounds have become major clinical problems due to dysregulated inflammation, impaired angiogenesis, and abnormal extracellular matrix (ECM) remodeling. Noncoding RNA (ncRNA), including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), serve as key molecules to regulate these pathological processes. These ncRNA also constructs a competitive endogenous RNA (ceRNA) network to precisely adjust miRNA activity and target gene expression. Through gene editing or chemical modification, exosomes achieve ncRNA delivery with high efficiency and targeting and show exciting promise in preclinical models. Combining with biomaterials such as hydrogels can prolong the exosome half-life and achieve the continuous release of ncRNA. In addition, researchers explore how machine learning (ML) and artificial intelligence (AI) could advance future therapeutic applications. Drug delivery system can be improved both by predicting personalized ceRNA networks for individual patients, and designing smart wound dressings that combine exosomes with hydrogel materials tailored to specific wound types. By integrating these recent advances, this review helps bridge basic research and the future creation of targeted chronic wound treatments.

Metastasis is a leading cause of mortality in breast cancer and is critically influenced by cell-extracellular matrix (ECM) interactions, mechanical forces, and cellular motility. In this study, we present a cell surface engineering approach using tris(2-carboxyethyl)phosphine (TCEP), a biocompatible thiol-modifying agent, to modulate the biomechanical behavior of breast cancer cells. TCEP treatment increased surface thiol availability, enhanced phosphorylation of focal adhesion kinase (FAK), and promoted the elongation of pFAK-positive focal adhesions, along with cytoskeletal remodeling and stronger cell-ECM adhesion. These molecular and structural changes corresponded with significantly reduced migration and invasion of MCF7 and MDA-MB-231 cells. Using traction force microscopy (TFM), we further observed increased intracellular tension and traction stress, providing quantitative insight into how surface modification regulates mechanotransduction. These findings highlight the potential of cell surface thiol engineering to control cancer cell adhesion and motility, providing a platform for future identification of clinically applicable redox-modulating agents.

This study aimed to examine the histological and mechanical effects of cryopreservation on human aortic tissues, focussing on storage duration and conditions. Assessments included smooth muscle cell integrity, elastic fibre preservation, and endothelial viability. Cryopreservation with dimethyl sulphoxide (DMSO) significantly reduced smooth muscle cell nuclei loss and maintained elastic fibre integrity. However, elastic fibre thickness increased after 12 months. Isolectin B4 staining showed reduced endothelial cell viability across all groups. No significant changes were observed in mucoid extracellular matrix accumulation or elastic fibre fragmentation. These findings suggest that cryopreservation with DMSO effectively maintains structural integrity for up to 12 months but requires refinement to address endothelial and biomechanical concerns. Cryopreserved aortic allografts demonstrated structural and functional performance when stored at low temperatures, confirming their viability for reconstructive surgeries. The study highlights the importance of the timely utilisation of cryopreserved grafts and optimising preservation techniques to advance surgical applications.

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited skin disorder caused by mutations in COL7A1. Patient-derived induced pluripotent stem cells (iPSCs) enable the personalized study of RDEB pathogenesis and potential therapies. However, current skin cell differentiation protocols via 2D culture perform suboptimally when applied to engineered 3D skin constructs (ESC). Here, we present an approach to source fibroblasts (iFBs) and keratinocytes (iKCs) from iPSC-derived skin organoids using an optimized differentiation protocol, and utilize them to engineer ESCs modeling wild-type and RDEB phenotypes. The resulting iPSC-derived skin cells display marker expression consistent with primary counterparts and produce ESCs exhibiting significant extracellular matrix remodeling, protein deposition, and epidermal differentiation. RDEB constructs recapitulated hallmark disease features, including absence of collagen VII and reduced iFB proliferation. This work establishes a robust and scalable strategy for generating physiologically-relevant, iPSC-derived skin constructs, offering a powerful model for studying RDEB mechanisms and advancing personalized regenerative medicine.

Over 30% of polytrauma patients with bone fractures suffer from impaired healing and nonunion due to persistent systemic inflammation. Existing biologic strategies for bone repair primarily focus on osteogenesis but are not designed to modulate systemic immune dysregulation, limiting their utility in the polytrauma setting. To overcome this, we developed a hyaluronic acid-based hydrogel (HA) incorporating osteogenic intrinsically disordered peptides (P2) and mesenchymal stem cells (MSCs) to promote bone regeneration and modulate inflammation simultaneously. MSCs entrapped in hydrogels containing P2 (HA + P2) exhibited increased cell viability, alkaline phosphatase activity, and calcium deposition under in vitro polytrauma conditions compared to MSCs in hydrogels alone (HA). We utilized a murine polytrauma model (4 mm femoral osteotomy + blunt chest trauma) in mice. We studied the inflammatory response and bone formation over 21 days in mice treated with (1) HA, (2) HA + P2, or (3) HA + P2 + MSCs. We observed that adding P2 enhanced bone mineralization at the fracture site, yet transplantation of MSCs with P2 further increased mineralization. Both HA + P2 and HA + P2 + MSCs groups attenuated the systemic inflammatory response to near healthy baseline values. The HA + P2 group significantly accelerated the first stages of fracture healing by upregulating genes encoding for collagen biosynthesis, modifying enzymes, and extracellular matrix (ECM)-receptor interaction. Mice treated with HA + P2 + MSCs exhibited transcriptional regulation resulting in the upregulation of key repair genes related to cell cycle control, E2F transcriptional regulation, and TP53-mediated DNA repair, alongside downregulation of inflammatory pathways (IL-2, IL-3, and IL-5 signaling) and improved fracture healing. This study demonstrated that the combination of intrinsically disordered peptides and mesenchymal stem cells in HA-based hydrogels enhances bone formation, modulates both local and systemic inflammation, and improves structural organization at the fracture site in polytrauma conditions.

Coronary artery disease (CAD) encompasses a spectrum of pathologies driven by atherosclerosis, trauma, inflammation, or other etiologies that compromise coronary morphology and function, ultimately leading to myocardial ischemia and infarction. While organ-on-a-chip (OOC) technology has emerged as a transformative tool for cardiovascular research, existing reviews have consistently marginalized coronary-specific pathophysiology, treating it merely as a subset of generic vascular biology. This review presents the first dedicated, critical analysis of microphysiological system (MPS) engineered explicitly as CAD-on-a-chip platform. We deliberately depart from generalized vascular models by exclusively evaluating systems designed to recapitulate the unique coronary-specific hallmarks: distinct geometric constraints, pro-inflammatory microenvironments, and dynamic hemodynamic shear stress profiles inherent to human coronary arteries. Following a concise introduction to OOC fabrication materials and techniques, we systematically present vessel-on-a-chip (VOC) models derived from diverse cellular sources. We then emphasize the biomedical applications of VOC in CAD field and analyze key CAD-specific pathological processes, including flow-mediated endothelial dysfunction, atherosclerotic plaque formation, plaque rupture-induced atherothrombosis, and coronary artery aneurysm. Finally, we critically discuss current limitations and outline future directions of OOC technology in CAD research. This review by focusing on the specific pathological features of CAD and the requirements for in vitro modeling, aim to establish a targeted knowledge framework to promote the clinical transformation of VOC technology in CAD diagnosis and treatment.

Two-dimensional (2D) cardiac models are widely used for cardiotoxicity screening but often lack structural and functional maturity of adult native tissue. Electrical stimulation (ES) enhances in vitro maturation, yet conventional waveforms (monophasic and symmetric biphasic) have shown limitations, including charge accumulation and possible cell hyperpolarization. Here, we introduce for the first time an asymmetric biphasic ES waveform that combines the advantages of monophasic and symmetric biphasic stimulation by reversing the current and reducing residual voltage. Asymmetric biphasic stimulation improved electrical functionality, calcium handling and contractility of neonatal rat cardiac cells, without triggering cellular stress. Additionally, cells subjected to asymmetric biphasic ES displayed a metabolic shift toward fatty acid oxidation, a hallmark of mature cardiomyocytes. Taken together, these findings highlight the novelty and efficacy of asymmetric biphasic stimulation in generating more physiologically relevant in vitro cardiac models, providing a promising alternative to standard ES protocols.

Peripheral nerve injuries (PNIs) affect thousands of patients yearly, often resulting in loss of function, sensation, and chronic pain. In critical-size defects, advanced surgical repair strategies often fail to restore full function. A key limitation is the lack of sustained, localized delivery of biological cues for axonal regeneration, such as growth factors. Glial-cell line-derived neurotrophic factor (GDNF) is known to promote axonal growth, Schwann cell migration, and neuronal survival, but uncontrolled release may cause axonal entrapment. We previously developed tissue-engineered nerve grafts (TENGs) composed of two neuronal populations connected by stretch-grown axons. In this study, we genetically modified the distal population to express human GDNF under a Tet-on inducible promoter, temporally controlling GDNF release through doxycycline administration. Modified TENGs survived implantation in a 1.5-cm rat sciatic nerve defect, supporting future studies. This approach offers a promising platform for spatially and temporally controlled neurotrophic factor delivery from tissue-engineered living scaffolds.

Bone tissue regeneration and fracture healing remain a significant challenge for physicians, with nonunion failures occurring in an estimated 5%-10% of bone-healing treatments. The autologous bone graft has long been the gold standard of treatment. However, these procedures suffer from persistent donor-site morbidity and extended surgery times, while still having high revision and nonunion failure rates. Cell therapies and tissue engineering strategies utilizing stem cells have been considered as promising alternatives to autologous bone grafts. Here, we explore the concept of using CRISPR-activation (CRISPRa) as a cell-engineering tool to drive osteogenesis without exogenous growth factors. We present a genome-wide CRISPRa screen in adipose-derived stem cells (ASCs) to identify upregulation targets that drive osteogenesis. Top targets from the screen, SPRED2 and ATXN7L3B, demonstrated significant increases in alkaline phosphatase activity and mineralization in monolayer and 3D culture. These results are the first evidence of these genes as osteogenic targets in ASCs.