Tissue-engineered heart valves (TEHVs) have been developed to overcome the limitations of current prosthetic valves, which lack growth, repair, and remodeling capacity. While early TEHV strategies relied on pre-seeded cells, recent approaches have shifted toward cell-free scaffolds designed to promote in situ tissue regeneration; however, the relative advantages and limitations of these strategies remain unclear. This review synthesizes evidence from preclinical and clinical studies of TEHVs, including fully synthetic biodegradable scaffolds, decellularized xenografts, decellularized allografts, engineered decellularized matrices, and cell-seeded constructs, with a focus on scaffold composition, recellularization, extracellular matrix (ECM) formation, and functional durability. Overall, cell-free TEHVs demonstrate the ability to recruit host cells and support tissue formation, but remodeling is frequently incomplete and heterogeneous, particularly in valve leaflets. Decellularized xenografts show limited durability due to persistent immunogenicity, whereas decellularized allografts provide the most consistent clinical performance but exhibit incomplete recellularization and variable long-term outcomes. Fully synthetic and engineered decellularized scaffolds enable in situ regeneration but are often associated with geometric instability and maladaptive remodeling. Cell-seeded TEHVs can enhance early endothelialization and matrix deposition; however, challenges remain in cell retention, survival, and regulation of remodeling, with no consistent long-term superiority. Taken together, neither purely cell-free nor cell-seeded strategies alone reliably achieve durable valve regeneration, and the primary challenge lies in controlling remodeling rather than the presence of seeded cells, supporting the development of integrated approaches that combine scaffold design with biological modulation to improve long-term valve function.
Background: Volumetric muscle loss (VML) significantly impairs the inherent regenerative ability of skeletal muscle, causing dysfunction and scar tissue formation. Current treatments are limited to functional muscle transplantation, posing many complications and incomplete functional recovery. Methods: To simulate the extracellular matrix microenvironment and promote vascularized muscle regeneration, we developed a bioactive composite hydrogel with the angiogenic and myogenic effect of strontium ions (Sr2+) and collagen type I (COL I), polyvinyl alcohol (PVA)/tannic acid (TA)/COL I/Sr2+ (PTCS). The physical properties of PTCS were characterized, including the mechanical properties, degradation, and release behavior. The in vitro influences of PTCS on C2C12 myoblasts and human umbilical vein endothelial cells (HUVECs) were evaluated via Cell Counting Kit-8, Live/Dead staining, wound healing, myotube differentiation, and Transwell assays. In addition, PTCS was implanted in the rat VML model and assessed for its effect on muscle regeneration in vivo. Results: The modulus of PTCS was similar to that of native rat muscle, and the degradation matched the muscle regeneration timeline. Controlled release of Sr2+ and COL I created a favorable microenvironment for vascular and muscular regeneration. PTCS facilitated the proliferation, migration, and differentiation of C2C12 myoblasts and enhanced the migration and invasion of HUVECs. Furthermore, the therapeutic effects of PTCS in vivo demonstrated a promoted vascular-specific marker CD31 expression, muscle fibers regeneration, and a decreased fibrosis area. Conclusions: These findings demonstrated that PTCS was a promising implantable biomimetic scaffold in skeletal muscle tissue engineering, and Sr2+ had a synergistic effect with COL I in muscle regeneration.
Objective: Osteoporosis is a chronic disease associated with decreased bone strength and a heightened susceptibility to fractures. Atractylodes macrocephala Koidz. (AMK) is a traditional Chinese herb that tonifies the spleen and invigorates qi, which helps to strengthen muscles and bones. In this study, AMK-derived exosome-like nanovesicles (AMKELNs) are studied to determine whether they function in osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) and in osteoporosis of ovariectomized (OVX) rats. Methods: AMKELNs were extracted from the rhizome of AMK by differential centrifugation, whose structure was visualized by transmission electron microscopy, and the particle size was determined by nanoparticle tracking analysis. A series of experiments, such as quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot, alkaline phosphatase (ALP) activity, and alizarin red staining, were conducted to evaluate the effect of AMKELNs on osteogenic differentiation of hBMSCs. Furthermore, AMKELNs were intraperitoneally injected into OVX rats for 12 weeks of treatment. Micro computed tomography (Micro-CT) and histological staining were performed to assess the effects of AMKELNs on osteoporosis. Results: AMKELNs with an intact bilayer membrane and an average size of 141.9 ± 0.5 nm were successfully internalized by hBMSCs and absorbed by Sprague-Dawley rats. Moreover, AMKELNs stimulated the osteogenic differentiation of hBMSCs by up-regulating the expression of superoxide dismutase 2 (SOD2). In the animal experiment (n = 5), AMKELNs could effectively preserve the bone mass of rats and improve the bone parameters. Conclusions: Our results indicate that AMKELNs represent a promising therapeutic method for osteoporosis. This study proposes a new theoretical perspective on bone tissue repair strategies based on a natural drug nano-delivery system.
Objectives: The development of biomaterials for bone tissue engineering requires a combination of suitable mechanical properties, bioactivity, and cytocompatibility. In this study, photocrosslinked polymer-ceramic composites based on poly(vinylpyrrolidone) (PVP), poly(ethylene glycol) (PEG), and pullulan were developed and reinforced with dicalcium phosphate dihydrate (DCPD, brushite) to obtain bioactive materials with enhanced biological performance. Methods: DCPD was synthesized via a wet precipitation method and incorporated into polymer matrices through UV-induced photopolymerization. The resulting composites were characterized in terms of swelling behavior, hardness, degradation in physiological conditions, surface morphology, and biological response. Cytocompatibility was assessed using direct and indirect cytotoxicity assays, proliferation studies, and scanning electron microscopy (SEM) evaluation of MC3T3-E1 preosteoblast adhesion and morphology. Results: The composition of the polymer matrix significantly affected the physicochemical properties of the materials. Increased PVP content resulted in higher hardness and more developed surface morphology, whereas DCPD incorporation reduced swelling and increased surface roughness. All materials exhibited satisfactory cytocompatibility, with cell viability remaining above the threshold specified by ISO 10993-5. Proliferation studies demonstrated progressive cell growth over time, particularly on DCPD-containing composites. SEM observations confirmed successful cell attachment and favorable cell-material interactions, with the most pronounced response observed for balanced PVP/PEG formulations reinforced with DCPD. Conclusions: The developed PVP/PEG/pullulan-DCPD composites demonstrated promising physicochemical and biological properties and may serve as preliminary bone-facing materials for future osteochondral tissue engineering applications. Further studies are required to investigate their osteogenic potential and long-term biological performance.
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with a complex pathogenesis and limited therapeutic options. Nanozymes, particularly carbon dots (CDs), offer a novel strategy for treating IBD owing to their enzyme-like catalytic activities and high biocompatibility. Traditional Chinese medicine (TCM) involves the use of rich sources of bioactive compounds with anti-inflammatory and antioxidant properties; however, the clinical application of these compounds is often hampered by their low solubility and bioavailability. This review explored the effects of TCM-derived CD nanozymes (TCM-CDs) on enhancing IBD therapy. The classification, green synthesis methods, and unique mechanisms of TCM-CDs, including reactive oxygen species scavenging, regulation of gut microbiota, and modulation of inflammatory signaling pathways, were summarized. Furthermore, the current limitations in material synthesis, biological uncertainty, and clinical translation challenges were discussed; an AI-driven framework was developed for future precision design and personalized IBD treatment. TCM-CDs represent promising nanoplatforms that synergize the multitarget therapeutic advantages of TCM with the catalytic versatility of nanozymes, offering new insights into next-generation IBD therapeutics.
