Regenerative Biomaterials最新文献

Diabetic kidney disease (DKD) and osteoporosis are closely linked, yet the underlying mechanisms remain incompletely understood. DKD mouse and rat models were established via combinatorial treatment with a high-fat diet and streptozotocin, which not only induced progressive renal dysfunction, but also triggered systemic osteoporotic changes, including reduced bone mineral density, trabecular thinning and impaired bone microarchitecture. Using single-cell sequencing, we demonstrate that DKD elevates the expression of Sfrp2 (secreted frizzled related protein 2) in glomerular mesangial cells (MCs), establishing MCs as a critical source of circulating secreted frizzled related protein 2 (SFRP2 protein). In turn, elevated SFRP2 potently inhibits the Wnt signaling pathway, suppresses osteoblast differentiation and promotes bone loss in diabetic mice. Exosomes, which exhibit a size range endowed with natural tropism for the renal mesangial space, hold promise as optimal delivery vectors targeting renal MCs. Exosomes loaded with siSfrp2 (siRNA against Sfrp2 mRNA) circulate into MCs after tail vein injection. In turn, exosome-mediated siSfrp2 delivery effectively reduces circulating SFRP2 levels, restores Wnt signaling and alleviates osteoporotic phenotypes in DKD mice. Moreover, in diabetic rat models, renal injury is accompanied by consistent osteoporotic defects and weakened implant osteointegration capacity. Exosome-mediated Sfrp2 knockdown in these rats significantly enhances implant osseointegration, further validating the renal-osteal axis. These findings establish a MCs-derived SFRP2-mediated renal-osteal axis, revealing that glomerular MC-secreted SFRP2 serves as a key molecular bridge linking kidney injury to bone loss. This mechanistic insight highlights SFRP2 and its main cellular source (MCs) as promising therapeutic targets for managing diabetic osteoporosis.

Excessive oxidative stress and dysregulated macrophage polarization-characterized by M1/M2 imbalance-drive chronic, persistent inflammation and represent key pathological mechanisms underlying impaired tissue repair in diabetic wounds; however, therapeutic strategies targeting both these processes remain limited. L-arginine (L-Arg) shows therapeutic potential through its antioxidant properties and ability to promote M1 macrophage polarization. Nevertheless, the mechanisms by which L-Arg regulates mitochondrial homeostasis to exert antioxidant effects remain unclear. Moreover, its clinical translation is hindered by poor retention, inadequate tissue penetration and damage induced by hypertonicity, thereby necessitating the development of innovative delivery systems. To address these limitations, we developed an L-Arg-loaded microneedle (L-Arg-MN) patch for controlled delivery. Our findings demonstrate that L-Arg alleviated hydrogen peroxide (H₂O₂)-induced cellular damage through activation of the Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) pathway, boosting antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)) and lowering malondialdehyde (MDA) levels. Mechanistically, L-Arg maintained mitochondrial homeostasis by upregulating peroxiredoxin 1 (PRDX1) expression, restoring mitochondrial membrane potential and enhancing adenosine triphosphate production. Furthermore, L-Arg suppressed M1 macrophage polarization and promoted M2 polarization through PRDX1-mediated mitochondrial metabolic pathways. In models of diabetic wounds, the L-Arg-MN patch markedly enhanced the wound healing process, accelerated wound closure, reduced concentration of reactive oxygen species (ROS), enhanced granulation tissue, collagen formation and increased M2 macrophage infiltration. This study elucidates how L-Arg reduces oxidative stress and enhances M2 macrophage polarization by regulating mitochondrial metabolism through the PRDX1 pathway. By integrating the metabolic and immunomodulatory properties of L-Arg with advanced drug delivery technology, the L-Arg-MN patch presents an innovative and efficient approach to treating diabetic wounds.

'Oral bone' primarily refers to the bones within the mouth, specifically the jawbones and the alveolar bone that supports teeth. Oral bone tissue defects are commonly caused by trauma, inflammation and surgical excision and their repair represents one of the core challenges in the field of oral medicine. The use of functional biomaterials for tissue regeneration has become a research focus in the field of damaged tissue treatment. However, following the implantation of biomaterials, the immune response induces the generation of reactive oxygen species (ROS) and the open and susceptible environment of oral bone predisposes it to redox imbalance, resulting in ROS accumulation and compromised repair. In response to this challenge, ROS-regulating biomaterials have developed into an effective platform for restoring redox balance. Despite this progress, current research lacks a systematic framework for the mechanism and design of biomaterials specifically addressing the special metabolism of oral bone. This review focuses on the physiological and pathological characteristics of oral bone, explores the interaction mechanisms between the oxidative stress and oral bone defects and provides a functional classification of regulation mechanisms. In addition, this review provides several corresponding suggestions for the development of targeted biomaterials according to the problems of existing ROS-regulating materials applied in oral bone repair.

Diabetes-induced chronic wound healing poses significant clinical and economic challenges. In the pathological context of diabetic wounds, the accumulation of reactive oxygen species (ROS) and inflammatory factors is exacerbated, impeding the transition of macrophages from the M1 to M2 phenotype, thereby leading to prolonged wound healing. Therefore, this study has developed an ultra-small tri-manganese tetroxide nanozyme with dual superoxide dismutase/catalase enzymatic activities, which exhibits excellent ROS scavenging performance. Under oxidative stress conditions, this nanozyme can alleviate mitochondrial damage and promote the transition of macrophages from the M1 to M2 phenotype, thereby mitigating the inhibition of cellular function caused by the inflammatory state through intercellular interactions. Furthermore, the application of this nanozyme in vivo has also contributed to the treatment of skin defects in streptozotocin-induced diabetic mice by alleviating inflammation and scavenging ROS. The dual-enzymatic nanozyme designed and prepared in this study, which scavenges ROS, can regulate the local immune microenvironment and intercellular interactions, providing a new strategy for the clinical treatment of diabetic wound healing.

Paraspinal muscle atrophy (PMA) is a common complication after spinal surgery, often leading to reduced spinal stability and prolonged discomfort. While mitochondrial dysfunction has emerged as a key contributor to PMA, existing therapies do not adequately address this underlying pathophysiology. In this study, we investigated the regenerative potential of plasma-derived mitochondria (pMT) as a cell-free and autologous biomaterial to mitigate PMA. Mitochondria were isolated from human peripheral blood and confirmed to maintain their structural integrity and respiratory activity. In an in vitro model of muscle atrophy, pMT treatment improved cell viability, enhanced ATP production and restored mitochondrial function. In a rat model of surgery-induced PMA, intramuscular injections of pMT led to improved muscle morphology, including increased fiber cross-sectional area, along with reduced mechanical hypersensitivity. Transcriptomic analyses revealed that pMT transplantation modulated key pathways related to mitochondrial biogenesis and oxidative phosphorylation, while downregulating pro-apoptotic signals. These findings were corroborated by protein-level assessments showing restoration of muscle-specific markers and normalization of mitochondrial homeostasis. Taken together, this study highlights the therapeutic potential of pMT transplantation in addressing mitochondrial dysfunction and promoting muscle regeneration following spinal surgery. These findings suggest that pMT may serve as a minimally invasive, scalable and autologous regenerative approach to restore skeletal muscle integrity in clinically relevant contexts.

Core-shell scaffold designs that mimic the biophysical structure of tendon extracellular matrix offer unique advantages for tendon repair. However, balancing the structural integrity of the scaffold with the desired material and biological properties remains challenging, limiting the effectiveness of the scaffold. Here, we present a new method for fabricating a core-shell scaffold with tailored properties for tendon tissue engineering. The scaffold core, designed for cell guidance, was created using direct ink writing, resulting in a helically interconnected fibre structure with controllable anisotropy and pore sizes. The mechanically reinforced shell, produced through uniaxial cold stretching of a laser-drilled sheet, featured microsurface ridges and through-hole arrays. The core-shell integration enabled sequential degradation and mechanical properties aligned with tendon tissue requirements, providing extended structural support and improved space for neotissue ingrowth. In vitro and in vivo studies confirmed the scaffold's non-cytotoxicity and superior tendon matrix regeneration, with increased collagen deposition and structural alignment compared to controls. These findings highlight the potential of the developed scaffold for advancing tendon repair applications.

Bioinert poly(methyl methacrylate) (PMMA) is widely employed as a bone cement material in orthopedic and trauma surgery applications; however, its susceptibility to bacterial infection and bioinert nature limits its clinical applications. In this study, we developed a PMMA-based bone cement incorporating a silver nanoparticle-carbon dots (AgNP@CDs) nanocomposite (∼70 nm) at concentrations (2 wt%) with a Young's modulus (324.74 ± 7.08 MPa) to simultaneously combat bacterial infections, minimize cytotoxicity and support tissue regeneration. The CDs stabilize and functionalize AgNPs, improving their dispersion and bioavailability while enabling the controlled and sustained release of antimicrobial ions through incorporation with bone cement. The antibacterial efficacy of the composite was thoroughly evaluated, revealing its ability to disrupt bacterial cell membranes, generate reactive oxygen species and inhibit bacterial growth. These mechanisms collectively contribute to a significant reduction in bacterial growth of up to ∼90% in both in vitro and in vivo studies. The incorporation of AgNP@CDs ensures sustained antimicrobial activity, preventing bacterial colonization by controlling the leaching of Ag ions. Biocompatibility assessments showed that the PMMA composite (PMMA@2Ag-CDs) significantly improved cell proliferation, adhesion and migration compared with pure PMMA bone cement. Additionally, histological analysis revealed that the PMMA group showed a fibrous layer thickness of 699 ± 35.32 µm, indicative of inflammation, while the PMMA@2Ag-CDs group reduced this thickness from 301.18 ± 22.42 µm on day 7 to 198.07 ± 15.21 µm on day 14, significantly decreasing inflammation. The PMMA@2Ag-CDs composite demonstrated better tissue integration, with organized collagen deposition and enhanced angiogenesis, indicating more efficient tissue regeneration. The reduced inflammation and improved tissue remodeling suggest that this composite promotes a more favorable tissue regeneration environment and minimizes complications. This study demonstrates that the PMMA@2Ag-CDs composite offers a promising solution for the prevention of infections and mitigation of inflammatory responses. Functionalization of bone cement through the incorporation of Ag nanoparticle-carbon dot nanocomposites is a promising strategy with potential practical applications in orthopedic and trauma surgery.

Reconstructing bone defects remains a significant challenge in clinical practice, driving the urgent need for advanced artificial grafts that simultaneously promote vascularization and osteogenesis. Addressing the critical trade-off between achieving high porosity/strength and effective bioactivity at safe ion doses, we incorporated strontium (Sr) into β-tricalcium phosphate (β-TCP) scaffolds with a triply periodic minimal surface (TPMS) structure using digital light processing (DLP)-based three-dimensional (3D) printing. Systematically screening Sr concentrations (0-10 mol%), we identified 10 mol% as optimal, leveraging the synergy between the biomimetic TPMS architecture, providing exceptional mechanical strength (up to 1.44 MPa at 80% porosity) and facilitating cell recruitment and precision Sr-dosing to enhance bioactivity. In vitro assays revealed that the Sr-TCP scaffold dose-dependently stimulated osteogenic differentiation and mineralization in mouse osteoblastic cell line (MC3T3-E1) cells, while also significantly enhancing the angiogenic capacity in human umbilical vein endothelial cells (HUVECs). In vivo studies indicated that the scaffold demonstrated synergistic osteogenic and angiogenic effects in rat femoral condylar defects, leading to marked improvements in bone healing. Collectively, this study establishes a novel design paradigm combining biomimetic topology with optimized ionic doping, resolving key limitations of conventional grafts and advancing the development of safe, highly effective biomaterials for vascularized bone regeneration.

Automated literature mining is key to building structured biomedical materials databases, yet current methods struggle with large publication volumes, complex entity relations and domain-specific terminology. We propose a hierarchical natural language processing (NLP) framework for extracting structured data from biomedical materials texts. Our pipeline uses named entity recognition (NER) to identify entities such as compositions, synthesis methods and properties. Sentence-level relation extraction captures direct associations (e.g. temperature, morphology), while a paragraph-level graph convolutional network (GCN) module resolves cross-sentence co-references. Rule-based templates enhance precision in specific cases. Extracted relations are integrated into a biomedical materials knowledge graph, enabling scalable and extensible data representation. Experiments show that the sentence-level model achieves 84.7% accuracy and the GCN-based module achieves 84.0%. This approach offers an efficient pipeline for structuring complex scientific texts, reducing manual effort and supporting large-scale knowledge extraction in biomedical materials and related domains.

Bacterial infection in the injured skin may threaten the wound repair and skin regeneration owing to aggravated inflammation. The multifunctional dressings with persistent antibacterial activity and improved anti-inflammatory capability are urgently required. Herein, a type of heterogeneous zinc/catechol-derived resin microspheres (Zn/CFRs) composed of zinc ions (Zn²⁺) and zinc oxide (ZnO) nanoparticles was developed to impart the methacrylamide chitosan (CSMA)-oxidized hyaluronic acid (OHA) hydrogel with a persistent Zn²⁺ release behavior. The Zn/CFRs synthesized via a one-step hydrothermal method exhibited a Zn²⁺-enriched surface and internal ZnO nanoparticles. Owing to the unique microstructure of the microspheres, the Zn/CFRs-functionalized hydrogel (CH-ZnCFR) was able to rapidly release Zn²⁺ in the initial phase and sustain the release of Zn²⁺ for 14 days. Importantly, CH-ZnCFR exhibited excellent anti-inflammatory property by facilitating the macrophage polarization, and also effectively inhibited the growth of Staphylococcus aureus and Escherichia coli. In addition, CH-ZnCFR showed excellent self-healing and tissue adhesion properties, and great cytocompatibility by improving fibroblast migration behavior in vitro. Moreover, CH-ZnCFR demonstrated outstanding therapeutic effects in a murine model of S. aureus-infected wounds, including effectively inhibiting bacterial growth, reducing inflammation, increasing the number of M2-type macrophages and facilitating collagen deposition, angiogenesis and tissue regeneration. Therefore, this Zn/CFRs-functionalized composite hydrogel represents a promising strategy for bacterial-infected wound healing and regeneration.