Regenerative Biomaterials
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2025
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IF 8.1
Wang Xueying,Liu Hongyi,Sun Mingjiang,Liu Aihua,Li Yan
Ultrathin strut Fe-based scaffolds have made significant progress in the field of vascular interventional devices, but the issues of slow degradation and insufficient biocompatibility at the cell/material interface remain unresolved. This study prepared a functionalized surface on Fe by Zn ion implantation (Zn/Fe). Zn/Fe preferentially releases the antioxidant element Zn in the early degradation due to Zn–Fe galvanic coupling corrosion. It facilitates the adhesion and proliferation of endothelial cells and mitigates the risk of oxidative stress. The degradation rate of Zn/Fe was about 1.6 times that of Fe after 56 days of implantation in the common carotid artery of rats, with a 36.1% reduction in lumen loss rate, demonstrating favorable in vivo biocompatibility. These findings provide valuable insights for the development of novel functionalized Fe-based scaffold medical devices.
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DOI
高影响因子
Regenerative Biomaterials
·
2026
·
IF 8.7
Huang Jian,Tang Chen,Wu Ye,Xiang Tao,Chen Keyi,Bao Xiaogang,Wang Bo,Ren Jie,Yin Jingbo,Yan Shifeng,Xu Guohua
Articular cartilage has limited self-repair ability, and effective therapies for defects remain challenging. Injectable hydrogels are attractive for cartilage tissue engineering as they can fill irregular defects and mimic the native extracellular matrix (ECM). However, current hydrogels often suffer from dense microstructures, poor mechanical stability, and inadequate biological signaling, restricting tissue regeneration. In this study, a multifunctional injectable hydrogel system based on oxidized dextran and carboxymethyl chitosan (ODex/CMCS) was developed by integrating degradable gelatin microspheres (GMs) and kartogenin-loaded crosslinked gelatin fibers (KGN@GFs). The GMs served as thermosensitive, dissolvable porogens that generated an interconnected porous structure within the hydrogels to enhance nutrient diffusion, cell infiltration, and tissue ingrowth, while the KGN@GFs provided sustained KGN release and additional mechanical reinforcement. The resulting composite hydrogels exhibited favorable injectability, self-healing capability, and a porous architecture conducive to cell survival and spatial organization. In vitro experiments demonstrated good cytocompatibility and significantly enhanced chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Furthermore, implantation in rabbit cartilage defect models revealed that the ODex/CMCS/KGN@GFs/GMs hydrogel effectively promoted hyaline-like cartilage regeneration and integration with surrounding tissue. Collectively, this work presents a structurally and functionally optimized injectable hydrogel system that synergistically combines biochemical and structural cues to promote cartilage repair.
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DOI
高影响因子
Regenerative Biomaterials
·
2025
·
IF 8.1
Li Huaping,Chen Quan,Liang Bihua,Deng Huiyan,Bi Chao,Peng Liqian,Chen Jiaoquan,Ou Shanshan,Zhang Luoyu,Chen Ziyan,Zhu Huilan
The impaired healing of diabetic wounds primarily stems from persistent inflammation, a hypoxic microenvironment, and heightened susceptibility to infection. However, most existing studies focus on simple functional stacking, rather than aligning with the dynamic pathological repair process, which hinders the maximization of therapeutic efficacy of the repair materials. In this study, an intelligently responsive, bilayer anti-fouling nanocomposite hydrogel (Ca@Q-E@SGH) was developed for spatiotemporally synergistic therapy via spatiotemporal drug and oxygen delivery strategies. Its core component (Ca@Q-E) consists of calcium peroxide encapsulated by phenylboronic acid-modified quaternary ammonium chitosan, with epigallocatechin gallate (EGCG) linked via boronate esters. This dynamic bond enables ROS/glucose-responsive EGCG release to reprogram macrophages from the M1 to M2 phenotype, mitigating early-stage inflammation. As the matrix degrades, sustained oxygen is released from CaO2, supporting vascularization during tissue remodeling. Furthermore, the bilayer hydrogel structure is designed to provide multiple protective functions: the lower layer rapidly crosslinks to encapsulate the functional nanoparticles, while the upper layer forms a highly hydrophilic anti-fouling coating that effectively prevents pathogen adhesion. Collectively, this integrated platform combines intelligent microenvironment-responsive drug release for antibacterial and anti-inflammatory effects, followed by sequential oxygen delivery aligned with the wound healing stages, along with physical anti-fouling protection. As a result, the treated wounds achieved a remarkable closure rate of 99.1% by day 14. This study presents a comprehensive strategy for diabetic wound management by seamlessly integrating smart anti-inflammatory action, prolonged oxygen supply, and efficient anti-fouling capacity into a single coordinated platform.
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高影响因子
Regenerative Biomaterials
·
2026
·
IF 8.7
Zhang Yuwei,Sun Zhaoyu,Liu Miao,Pang Jinxin,Huang Shanshan,Liu Hongyang,Zheng Huabin,Guan Siyu,Li Jie,Feng Yifan,Ouyang Jiang,Xu Tao,Du Wen
Type 1 diabetes (T1D) arises from autoimmune destruction of pancreatic β-cells, leading to lifelong dependence on exogenous insulin. Clinical islet transplantation offers a potential cure by restoring endogenous insulin secretion; however, its success is critically limited by poor post-transplant vascularization and oxygen deprivation, which cause over 70% of transplanted islets to undergo early necrosis or apoptosis. To address these challenges, we developed an injectable, biodegradable dual-functional hydrogel composed of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMC). This polysaccharide-based platform co-delivers vascular endothelial growth factor (VEGF) and an oxygen-carrying perfluorotributylamine (PFTBA) nanoemulsion, enabling simultaneous enhancement of angiogenesis and oxygenation within the graft microenvironment. The OHA/CMC hydrogel exhibited excellent biocompatibility, tunable gelation, and sustained release of both oxygen and VEGF. In vitro, hydrogel-encapsulated islets demonstrated markedly improved resilience under hypoxic stress, exhibiting an 8.6-fold increase in viability after 6 hours and a 4.0-fold enhancement in glucose-stimulated insulin secretion (GSIS) after 48 hours under 0% O2. In streptozotocin-induced diabetic mice, transplantation with the OHA/CMC–PFTBA–VEGF hydrogel enabled rapid restoration of endogenous insulin secretion, reversal of severe hyperglycemia, prolonged graft function, and enhanced neovascularization at the implant site. Collectively, this multifunctional hydrogel represents a promising and translatable therapeutic platform for improving islet transplantation outcomes in T1D and potentially advancing broader applications in regenerative medicine and complex tissue engineering.
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DOI
高影响因子
Regenerative Biomaterials
·
2026
·
IF 8.7
Chen Xianglong,Gao Ren,Liang Xinyue,Liu Kun,Wei Zhong,Wu Xiaopei,Goto Takashi,Xiong Chengjie,Xu Feng,Dai Honglian
Peripheral nerve injury (PNI) triggers excessive oxidative stress and inflammation that impede nerve regeneration, leading to target organ atrophy and incomplete functional recovery. Conventional drug-loaded nerve conduits release anti-inflammatory drugs sustainably via filled hydrogels, requiring a precisely engineered hydrogel systems to match drug release kinetics without impeding regenerating nerve tissue growth. Meanwhile, constructing complex conduit systems may introduce potential cytotoxic factors and induce aseptic inflammation via acidic degradation products. Herein, we fabricated a ROS-scavenging CS-LA/P(MMD-CL) composite nerve conduit with rapid photo-crosslinking (365 nm UV irradiation, photoinitiator-free) via integrating lipoic acid-modified chitosan (CS-LA) hydrogel into oriented P(MMD-CL) conduit. Disulfide bonds in CS-LA scavenged ROS to alleviate oxidative stress, modulate inflammatory factor expression and resolve excessive inflammation, while the oriented P(MMD-CL) provided physical support and directional guidance for axon growth. In vivo studies on SD rats revealed that CS-LA/P(MMD-CL) promoted nerve regeneration through enhancing cell proliferation and angiogenesis, improving maturity of regenerative peripheral nerve, mitigating gastrocnemius atrophy and promoting nerve function recovery (SFI: -77.51 ± 1.51), and exhibited great biosafety—no organ damage from degradation byproducts. This simple, multifunctional composite conduit effectively modulates the PNI microenvironment and promotes peripheral nerve regeneration, offering a promising strategy for PNI repair.
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2026
·
IF 8.7
Shen Yiding,Dong Yilong,Hua Peng,Luo Hongyu,Shen Xinkun,Fang Kai,Hou Lingzhuo,Zheng Yeyi,Li Gaowen,Jin Litai,Yuan Yongping,Ma Pingping
Oral and maxillofacial surgeries or trauma (e.g., impacted tooth extraction, jaw fracture, or tumor resection) often lead to concurrent peripheral nerve injury and bone defects, while current collagen/gelatin sponges offer limited therapeutic effects. To address this challenge, we developed innovative electrospun scaffolds (MOF2, MOF4, and MOF6) by in situ synthesis of 3,5-dihydroxybenzoic acid/zinc (DHBA/Zn-MOF) hybrids within a gelatin/polycaprolactone matrix. In vitro, Schwann cells treated with material extracts exhibited enhanced migration, regulated myelin-associated genes (Ngf/Pmp22 upregulated, Ncam downregulated), and increased NGF protein expression via the PI3K pathway. Co-cultured PC12 cells showed increased neurite outgrowth, confirming neural repair potential. Osteoblasts exposed to material extracts showed elevated alkaline phosphatase activity, enhanced mineralization, and upregulated osteogenic genes (Runx2, Alp, and Opg), verifying osteogenic capacity. In vivo, MOF6 scaffolds achieved superior motor function recovery in a rat sciatic nerve crush model (evidenced by increased compound muscle action potentials and reduced gastrocnemius muscle atrophy) and promoted trabecular bone formation in a rat skull defect model (validated by micro-CT and histological analyses). These findings underscore the dual-functional capability of DHBA/Zn-hybrid scaffolds to simultaneously promote nerve repair and bone regeneration, offering a promising therapeutic approach for complex neuro-bone composite injuries in clinical practice.
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2025
·
IF 8.1
Wu Qilong,Fang Chao,Wang Taixia,Peng Qiuxia,Zhang Kun,Wang Dan,Xu Shihao
Sepsis, a systemic inflammatory response syndrome, causes severe immune dysfunction and is associated with high mortality because of the lack of effective clinical interventions. To address the pathogenesis of sepsis, such as bacterial infection and the exacerbation of inflammation and oxidative stress, an acidity-activated polylysine (PLL)-based copolymer self-assembly (PPDD) was developed. This material was synthesized by conjugating polyethylene glycol-modified PLL (PEG-PLL) with 2,7-dichlorofluorescein diacetate (DCFH-DA). PPDD, with its PLL-derived antibacterial and antioxidant properties, can scavenge reactive oxygen species (ROS), mitigate inflammation and eliminate bacteria. These combined actions help alleviate the symptoms of sepsis and improve survival rates. In vitro and in vivo experiments confirmed that this approach can rapidly neutralize ROS, significantly reduce pro-inflammatory cytokine cascades and effectively clear bacteria, thereby improving physiological stability and survival rates. Notably, Day-14 survival reached 80% in the PPDD-treated group compared with 20% in septic controls. More significantly, when the PPDD copolymer self-assembles into the acidic sepsis microenvironment, it disassembles and reconfigures from a spherical to an ellipsoidal structure. This acidity-activated structural transformation exposes more bioactive components for ROS scavenging, which is beneficial for removing oxidative stress, killing bacteria, reducing inflammation and alleviating sepsis. Following PPDD administration, systemic levels of TNF-α, IL-6, IL-10 and CRP were reduced by 38.1%, 46.0%, 76.7% and 32.9%, respectively, confirming its robust anti-inflammatory effect. Additionally, the conjugated DCFH-DA, a cell-permeable fluorescent probe, enables monitoring of oxidative stress and tracing the evolution of sepsis, especially after treatment. A comprehensive biosafety assay revealed no detectable hemolysis or organ toxicity, substantiating the translational potential of this platform. Our biocompatible and acidic sepsis environment-responsive PPDD paves a solid foundation for the clinical diagnosis and treatment of sepsis.
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DOI
高影响因子
Regenerative Biomaterials
·
2026
·
IF 8.1
Zhou Xiaosong,Wang Zongliang,Wang Yu,Guo Min,Zhang Peibiao
Repairing orbital bone defects remains a complex challenge in craniofacial surgery. Existing bone repair materials are plagued by issues such as intricate preparation processes and inadequate consideration of the spatiotemporal characteristics of bone healing. This study aimed to enhance the osteoinductive activity of poly (glycolide-co-caprolactone) (PGCL)-based materials through bicomponent modification, thereby providing a basis for the design of clinical bone repair materials. Hydroxyapatite/calcium sulfate/PGCL (HA/CS/PGCL) composite microspheres were fabricated via electrostatically assisted spray evaporation (ESASE). Their physicochemical properties and in vitro/in vivo osteogenic efficacy were evaluated using degradation-mineralization assays, MC3T3-E1 cell differentiation assessments and a rabbit orbital bone defect model. Innovatively, CS mesocrystal pore structure regulation was introduced to synergize with HA, achieving multidimensional optimization of surface hydrophilicity, sequential calcium ion release and mechanical properties. Results showed that in vitro mineralization formed native-like hydroxyapatite structures within 14 days. On HA/CS/PGCL surfaces, the proliferation activity of MC3T3-E1 cells reached 1.8 times that of the PGCL group after 7 days, with a 1.6-fold increase in alkaline phosphatase activity. In vivo, the composite microspheres achieved a new bone volume ratio (BV/TV) of 78.72% at 10 weeks, resulting in complete closure of the bone defect. Their trabecular structural parameters (trabecular thickness, Tb.Th; trabecular number, Tb.N) outperformed those of the single-component groups. Histological staining confirmed their ability to induce ordered collagen arrangement and the formation of dense new bone. In conclusion, the HA/CS synergistic modification strategy achieved the sequential release of calcium ions during bone repair and spatial regulation of the microsphere surface pore structure. The superior performance of HA/CS/PGCL microspheres in repairing complex bone defects lays an experimental foundation for clinical translation. Further research into the interactions between ion release and cell signaling is warranted.
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DOI
高影响因子
Regenerative Biomaterials
·
2026
·
IF 8.7
Jin Yanglei,Liu Qixue,Song Linran,Zhai Xinrang,Li Huimin,Wang Qi,Zhang Xianzhu,Chen Weiyu,Wei Wei,Teng Chong
Bone defects represent a significant clinical challenge, frequently resulting in nonunion and impaired function. Although autologous bone grafts are considered the gold standard owing to their excellent biocompatibility, their application is constrained by limited donor availability, thereby driving the need for alternative biomaterials. In this study, we report the synthesis of copper-aluminum layered double hydroxide (CuAl-LDH) nanosheets as a bioactive platform for bone regeneration. The nanosheets were systematically characterized using transmission electron microscopy, energy-dispersive spectroscopy and dynamic light scattering, confirming uniform morphology, precise elemental composition and colloidal stability. To enable localized therapeutic delivery, CuAl-LDH nanosheets were incorporated into gelatin methacryloyl (GelMA) hydrogels to form a nanocomposite hydrogel (Gel-CAL). Mechanical testing demonstrated that tuning the CuAl-LDH concentration (0.01–0.1 wt%) significantly enhanced the compressive modulus of the hydrogel, while rheological analysis revealed rapid light-induced gelation kinetics, making it suitable for minimally invasive, in situ implantation. The nanocomposite exhibited sustained release of Cu2+ ions over 40 days and displayed strong antibacterial activity against Escherichia coli. In vitro studies using rat bone marrow mesenchymal stem cells showed that Gel-CAL effectively reduced intracellular reactive oxygen species levels and upregulated key osteogenic markers, including alkaline phosphatase. In a rat subchondral bone defect model, micro-computed tomography and histological analyses at 5 weeks post-implantation revealed that Gel-CAL induced a significantly higher new bone volume fraction compared to GelMA alone. These results demonstrate that CuAl-LDH nanosheets serve as a multifunctional biomaterial that integrates mechanical reinforcement, antibacterial properties and osteogenic stimulation, offering a promising strategy for bone regeneration.
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DOI
高影响因子
Regenerative Biomaterials
·
2026
·
IF 8.7
Cao Xin,Wang Yang,Xu Yuanhang,Liang Nai,Xu Jiabao,Li Xinyun,Ye Cong,Zhao Caichou
The management of diabetic wounds remains clinically challenging, primarily owing to three interrelated pathological mechanisms: excessive accumulation of reactive oxygen species (ROS), dysregulated angiogenesis, and sustained, non-resolving inflammation. To address these issues, we developed a multifunctional 3D-printed nanoparticle enhanced bionic skin (3D-NEBS) by integrating polydopamine-gallium-arginine nanoparticles (PDA-Ga-LArg) into a self-healing hydrogel matrix composed of oxidized Tremella fuciformis polysaccharide, carboxymethyl chitosan, and fish gelatin. The resulting dressing exhibited mechanical adaptability, pH-responsive release, robust ROS-scavenging capacity and targeted immunomodulatory activity. In vitro, 3D-NEBS promoted M2 macrophage polarization, reduced inflammation, enhanced nitric oxide (NO) production, and improved endothelial cell migration and tube formation. Broad-spectrum efficacy was confirmed, with significant growth inhibition observed against S. aureus and E. coli. In a diabetic rat model, 3D-NEBS achieved 92.79% ± 0.39% wound closure within 14 days, with enhanced collagen deposition and neovascularization. Transcriptomic analysis revealed upregulation of pathways related to collagen synthesis, antioxidant response, and immune regulation. This study presents a synergistic hydrogel-nanoparticle platform with strong potential for diabetic wound repair.
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DOI
高影响因子
Regenerative Biomaterials
·
2026
·
IF 8.7
Zhang Junjiang,Chang Yuqi,Zhou Yiwen,Zhou Yang,Li Jiayin,Wang Feng,Zhou Zhimin,Sui Lei,Li Yanjing
Maxillofacial bone defects present a major challenge in clinical practice. Bone graft and bone tissue engineering are limited by various side effects and potential risks, while local drug delivery is regarded as a convenient and efficient strategy for bone repair and regeneration. However, for bone tissue regeneration, drug delivery system should not only release osteogenic drugs, but also possess an appropriate morphology to provide structural support for cell proliferation and differentiation. Polymeric non-spherical counterparts may offer new osteogenic properties through altered cellular interactions, biodistribution, and immune responses, compared with spherical drug carriers. Poly(lactic-co-glycolic) acid (PLGA) has been widely used to prepare various drug carriers due to its excellent biocompatibility and controllable biodegradation. Shape regulation, surface modification, and drug incorporation are effective approaches to impart distinct functions to PLGA particles for various biomedical applications. However, PLGA has inherent limitations, including poor hydrophilicity, acidic degradation products, and a lack of functional ligands for cell attachment, which hinder its effectiveness in bone regeneration. To solve these problems, natural proteins were utilized to improve the bone/cartilage regeneration of polymeric particles/scaffolds through surface modification or physical complex due to their excellent biocompatibility and biodegradability.In this study, we successfully developed simvastatin (SIM)-loaded disc-shape PLGA microparticles with coarse surface (dPLGA) using W1/O/W2 followed by silk fibroin (SF) coating for hydrophilicity and biocompatibility improvement. In vitro and in vivo experiments revealed that SF-modified SIM-loaded dPLGA (SF-SIM@dPLGA) significantly promotes the osteogenic differentiation of stem cells and bone regeneration in cranial bone defects, indicating the superior osteoconductive and osteoinductive advantages arising from the physical morphology of particles and chemical effect. Additionally, SF-SIM@dPLGA demonstrated improved tissue adhesion and hemostatic ability. This novel PLGA non-spherical particle-based local delivery system provides a feasible strategy for practical maxillofacial bone repair due to the simple preparation procedures and enhanced bone regeneration performance.
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2026
·
IF 8.7
Chen Jingdi,Hao Xiaotian,Xian Chunxing,He Xiang,Wang Taoran,Gao Jiakai,Liu Tao,Wu Wei,Yang Zhao,Bi Long
Repairing segmental bone defects remains difficult because conventional bone substitutes rarely integrate immunomodulation with efficient tissue regeneration. To address this limitation, zinc-silicate-collagen-hydroxyapatite (ZCH) composites were developed wherein the incorporation of zinc allows controlled material degradation and imparts immunoreactive properties. The addition of moderate concentrations of zinc silicate (<0.337 M) maintained good biocompatibility while enabling tuneable degradation rates and bioactivity. Among the composites, the composite containing 0.224 M zinc silicate (10ZCH) exhibited the most favourable balance between material degradation and bone regeneration and promoted accelerated angiogenesis and osteogenesis. Mechanistic studies revealed that 10ZCH transiently activated M1 macrophages and promoted their polarization towards the proregenerative M2 phenotype by activating the JAK/STAT pathway. These findings demonstrate that rational zinc incorporation can orchestrate immune responses, improve material resorption, and promote rapid tissue repair. This work provides an innovative design concept for fabricating immune-responsive and resorbable bone graft substitutes that couple degradation dynamics with regenerative efficacy.
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DOI
高影响因子
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