ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Xiao Yu,Chao Li,Jie Cui,Hao Feng,Yangfan Ding,Jiahui Song,Pengfei Cai,Liang Chen,Mohamed EL-Newehy,Meera Moydeen Abdulhameed,Xiumei Mo,Yu Han,Binbin Sun
Achilles tendon sleeve avulsions often involve tissue defects. Standard bone tunnel fixation risks tunnel enlargement, inflammation, and graft failure. Native tendon and bone tissue exhibit inherent bioelectrical properties whose disruption impedes healing. To address these, the study developed electroactive, anti-inflammatory sutures featuring a strong polylactic acid (PLA) micron yarn core and a conductive poly(3,4-ethylenedioxythiophene)/hydroxyethyl cellulose/glycerol/chondroitin sulfate/PLA (PEDOT/HEC/glycerol/CS/PLA) nanofibrous shell. A novel synthesis strategy enabled EDOT polymerization templated by HEC, eliminating the need for poly(styrene sulfonate) (PSS), oxidants, or catalysts and allowing direct electrospinning. In vitro, it can regulate macrophage polarization and enhance tenocytes and bone marrow mesenchymal stem cell (BMSCs) proliferation and differentiation. In a rabbit Achilles tendon avulsion model, the suture enables secure tendon-to-bone fixation via calcaneal bone tunnels. At 12 weeks post-operation, the suture exerts anti-inflammatory effects by modulating CD206/CD86 expression. Electroactive suture significantly enhances tendon regeneration and bone formation within the tunnels, and achieves robust tendon-to-bone integration at the interface, markedly improving fixation stability. In summary, this electroactive, anti-inflammatory suture effectively promotes tendon-bone regeneration for repairing Achilles tendon sleeve avulsions.
研究领域:
生物材料
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组织工程
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再生医学
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生物医学工程
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骨科手术
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纳米技术
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高分子科学
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免疫调节
✓ 已验证
产品关联
DOI
高影响因子
Applied Materials Today
·
2024
·
IF 7.2
Xiuhong Huang,Liqin Zheng,Pengfei Li,Ziling Lin,Shaohong Huang,Changren Zhou
Bone defects have been a tough clinical challenge. The natural trabecular tissue reflects a balance between the minimal metabolic cost of maintenance and maximal network stability, with mitochondria being the energy suppliers for osteogenesis. Herein, a 3D printed trabecular bone-templated scaffold composed of polylactide (PLA) modified with europium (III)-organic ligands (polydopamine and chitooligosaccharide, PDA/COS@Eu) was fabricated (denoted as Tra-PLA/PDA/COS@Eu) to augment bone repair by facilitating mitochondrial function. First, the trabecular bone templated-scaffold provides superior mechanical performance and permeability in contrast to a computer aided designed (CAD) scaffold under a same volume fraction. Tra-PLA/PDA/COS@Eu scaffold up regulated PI3K/AKT/S6K/HIF-1α pathway and significantly promoted BMSCs proliferation and osteogenic differentiation. In addition, Tra-PLA/PDA/COS@Eu scaffold provided anti-inflammatory environment by promoting macrophages M2 polarization through COS, and significantly stimulated BMSCs osteogenesis with enhanced mitochondrial function and biosynthesis. Remarkably, Eu ions are the key ingredient in enhancing mitochondrial function and biosynthesis in BMSCs. Further studies showed that the above-mentioned facilitations in a rabbit bone defect model were found to be more significant with trabecular bone-templated scaffolds, as opposed to CAD scaffolds. In summary, this novel trabecular bone-templated scaffold targeting mitochondrial function has the potential to become an effective method in the treatment of large bone defects.
研究领域:
生物材料
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组织工程
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生物医学工程
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再生医学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2025
·
IF 14.1
Chenglong Wang,Zeyu Shou,Chengwei Xu,Kaiyuan Huo,Wenjie Liu,Hao Liu,Xingjie Zan,Qing Wang,Lianxin Li
Osteointegration, the effective coupling between an implant and bone tissue, is a highly intricate biological process. The initial stages of bone-related immunomodulation and cellular colonization play crucial roles, but have received limited attention. Herein, a novel supramolecular co-assembled coating of strontium (Sr)-doped metal polyphenol networks (MPN) modified with c(RGDfc) is developed and well-characterized, for eliciting an early immunomodulation and cellular colonization. The results showed that the (Sr-MPN)@RGD coating significantly regulated the polarization of macrophages to the M2 phenotype by controllable release of Sr, and promote the initial adhesion of bone marrow mesenchymal stem cells (BMSCs) by RGD presented on MPN. Notably, the (Sr-MPN)@RGD attenuated osteoclast differentiation and oxidative stress as well as enhanced osteoblast differentiation and angiogenesis due to macrophage polarization toward M2 phenotype, which in turn has a profound effect on neighboring cells through paracrine signaling. In vivo results showed that the (Sr-MPN)@RGD coating manifested superior osseointegration and bone maturation to the bare Ti-rod or Ti-rod coated with MPN and Sr-MPN. This work contributed to the design of multifunctional implant coatings that address the complex biological process of osteointegration from the perspective of orchestrating stem cell recruitment with immunomodulatory strategies.
研究领域:
生物材料
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组织工程
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免疫学
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细胞生物学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Shue Jin,Zeyu Luo,Yongrui Cai,Jing Wen,Pengyu Lu,Xiaoxue Fu,Ping Mou,Anjin Chen,Weikun Meng,Jidong Li,Zongke Zhou,Weinan Zeng
Patients with clinical bone defects often experience varying degrees of muscle injury. Due to the high heterogeneity of hard and soft tissue structures, the integrated treatment of muscle injuries associated with bone defects remains a challenge. To address this challenge, this study proposes the construction of a heterogeneous bilayered electrospun nanofibrous scaffold based on the structural heterogeneity of bone and muscle to guide bone-muscle regeneration. The oriented fiber layer of the asymmetric bilayered scaffold promoted myofibroblast orientation and myogenic differentiation, whereas the random fiber layer promoted bone marrow mesenchymal stem cells (BMSCs) differentiation. Furthermore, immobilizing BMSCs-derived exosomes (BMSCs-Exo) on a heterogeneous bilayered scaffold via surface chemical modification of PEI enhances angiogenesis and immunoregulation. The foreign body response and muscle repair effect of the exosome-laden scaffolds were evaluated by subcutaneous implantation and a volumetric muscle loss model in mice. The performance of guided bone regeneration was assessed using a critical-sized cranial bone defect model in rats. BMSCs-Exo-functionalized heterogeneous bilayered electrospun nanofibrous scaffolds have great application potential in repairing bone-muscle injury.
研究领域:
组织工程
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再生医学
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生物材料
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Hu Chuan,Huang Ruipeng,Xia Jiechao,Hu Xianjing,Xie Dingqi,jin Yang,Qi Weiming,Zhao Chengliang,Hu Zhijun
Background The incidence of osteochondral defects caused by trauma, arthritis or tumours is increasing annually, but progress has not been made in terms of treatment methods. Due to the heterogeneous structure and biological characteristics of cartilage and subchondral bone, the integration of osteochondral repair is still a challenge.Results In the present study, a novel bilayer hydrogel scaffold was designed based on anatomical characteristics to imitate superficial cartilage and subchondral bone. The scaffold showed favourable biocompatibility, and the addition of an antioxidant nanozyme (LiMn2O4) promoted reactive oxygen species (ROS) scavenging by upregulating antioxidant proteins. The cartilage layer effectively protects against chondrocyte degradation in the inflammatory microenvironment. Subchondral bionic hydrogel scaffolds promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) by regulating the AMPK pathway in vitro. Finally, an in vivo rat preclinical osteochondral defect model confirmed that the bilayer hydrogel scaffold efficiently promoted cartilage and subchondral bone regeneration.Conclusion sIn general, our biomimetic hydrogel scaffold with the ability to regulate the inflammatory microenvironment can effectively repair osteochondral defects. This strategy provides a promising method for regenerating tissues with heterogeneous structures and biological characteristics.Graphical abstract
研究领域:
组织工程
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再生医学
·
生物材料
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骨科
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干细胞生物学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Peipei Feng,Chaonan He,Guanrong Li,Jin Li,Yang Luo,Yaoqi Chen,Yun Tang,Jingyun Ma,Chunhai Ke
Cartilage repair remains a formidable challenge because of its limited regenerative capacity. Construction of a biomimetic hydrogel matrix that can induce cell aggregation is a promising therapeutic option. Cell aggregates are more beneficial than dissociated cells for improving survival and chondrogenic differentiation, thereby facilitating cartilage repair. Herein, we report a light-cured injectable composite hydrogel with cellular aggregation properties for cartilage defect repair that combines methacrylated chitosan (CSMA) and a methacrylate-modified decellularized extracellular matrix (dECMMA). The CSMA promotes cell aggregate formation by enhancing cadherin expression. The dECMMA retains many inherent components and bioactive factors, thereby providing a more natural microenvironment for cell proliferation and differentiation. By precisely adjusting the compositions of the CSMA and dECMMA, it was possible to fine-tune their physicochemical properties and biochemical cues. The results showed that a composite hydrogel composed of 2 % (m/v) CSMA and 5 % (m/v) dECMMA exhibited good injectability, appropriate degradability and mechanical properties, and regulated the formation of bone marrow mesenchymal stem cell aggregates. Transplantation of the composite hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs) into a cartilage defect model demonstrated effective hyaline cartilage repair. Thus, light-cured injectable composite hydrogels embedded with BMSCs holds clinical promise for cartilage defect repair.
研究领域:
组织工程
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再生医学
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生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Yifan Lu,Ze-Yu Wang,Jianhong Xiao,Zhengyi Zhao,Xiaoyu Liao,Huai-Ling Gao,Duohong Zou
Treatment of osteochondral (OC) defects is still an immense challenge in clinic due to lack of satisfactory strategy to simultaneously regenerate both cartilage and subchondral bone. Herein, we propose an effective bottom-up strategy by developing a type of multifunctional chitosan-based nanocomposite microgels as the building blocks to repair OC defects. The microgels are biocompatible, and biodegradable, and have a hierarchical nanofibrous structure, mimicking the structural feature of extracellular matrix (ECM) to facilitate cell attachment and proliferation. Additionally, β-tricalcium phosphate (β-TCP) nanoparticles are incorporated in the microgels not only to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but also to facilitate the loading of transforming growth factor beta 1 (TGF-β1). For reconstructing OC defects, pure microgels are implanted at the bottom layer of the OC defects in rat knee joints to promote osteogenesis, while the microgels loaded with TGF-β1 are implanted at the top layer of the OC defects to promote cartilage regeneration. This modular microgel system results in simultaneous regeneration of cartilage and subchondral bone in OC defects, which is expected as a promising way for repairing other complex tissue defects in the field of tissue engineering.
研究领域:
组织工程
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生物材料
·
再生医学
✓ 已验证
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Kai Yuan,Yiqi Yang,Yixuan Lin,Feng Zhou,Kai Huang,Shengbing Yang,Weiqing Kong,Fupeng Li,Tianyou Kan,Yao Wang,Caiqi Cheng,Yakun Liang,Haishuang Chang,Jie Huang,Haiyong Ao,Zhifeng Yu,Hanjun Li,Yihao Liu,Tingting Tang
The specific mechanisms underlying bacteria-triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria-induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7-dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D-printed scaffold is designed with reactive oxygen species (ROS)-responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin-1 (Fer-1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.
研究领域:
细胞生物学
·
干细胞研究
·
组织工程
·
再生医学
·
生物医学工程
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Caiping Yan,Pengrui Zhang,Qiwei Qin,Ke Jiang,Yue Luo,Chao Xiang,Jiangtao He,Lu Chen,Dianming Jiang,Wenguo Cui,Yuling Li
The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
骨生物学
·
血管生物学
·
干细胞研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2022
·
IF 0
Xiaoyan Wang,Weijia Zheng,Zhenzu Bai,Shan Huang,Kai Jiang,Haoming Liu,Long Liu
There is a significant clinical demand for bone repair materials with high efficacy. This study was designed to fabricate nanofibrous scaffolds to promote bone defect regeneration using magnesium doped mesoporous bioactive glass (MBG), a fusion protein Osteocalcin-Osteopontin-Biglycan (OOB), silk fibroin (SF) and nerve growth factor (NGF) for facilitating accelerated bone formation. We found that MBG adsorbed with OOB ( [email protected] ) as core, and SF adsorbed with NGF ( [email protected] ) as shell to fabricate the nanofibrous scaffolds ( [email protected] / [email protected] ) through coaxial electrospinning. [email protected] / [email protected] scaffolds could effectively mimic the component and structure of bone matrix. Interestingly, we observed that [email protected] / [email protected] scaffolds could substantially promote bone mesenchymal stem cells (BMSCs) osteogenesis through stimulating Erk1/2 activated Runx2 and mTOR pathway, and it could also activate the expression level of various osteogenic marker genes. Intriguingly, [email protected] / [email protected] scaffolds could also enhance BMSCs induced neural differentiation cells differentiated into neuron, and activate the expression of the different neuron specific marker genes. Moreover, it was found that [email protected] / [email protected] scaffolds accelerated bone regeneration with neurogenesis, and new neurons were formed in Haversian canal in vivo . Consistent with these observations, we found that Erk1/2 and mTOR signaling pathways also regulated osteogenesis with the neurogenesis process from RNA sequencing result. Overall, our findings provided novel evidence suggesting that [email protected] / [email protected] scaffolds could function as a potential biomaterial in accelerating bone defect regeneration with neurogenesis, as well as in recovering the motor ability and improving the quality of life of patients.
研究领域:
材料科学
·
组织工程
·
生物医学工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
Applied Materials Today
·
2024
·
IF 7.2
Zhaohui Dang,Weihua Huang,Xiayu Cai,Jiandong Ye,Weikang Xu
Most bone filler materials currently achieve bone regeneration by mimicking the natural bone extracellular matrix. However, it is difficult for these materials to replicate the structural functions and bioactivities, including immunomodulation, of natural bone perfectly to reduce inflammation and promote bone regeneration synergistically. Repairing bone defects with scaffolds using a decellularised extracellular matrix (dECM) as a matrix material is an important clinical application and research direction. Here, we processed bovine cancellous bone via an optimised combination of decellularisation methods and preferred dECM, which has the shortest processing time and lowest immunogenicity. Hexagonal mesoporous silica (HMS)/poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with bone morphogenetic protein-2 (BMP-2) were prepared using the complex emulsion method. The HMS/PLGA microspheres had longer cytokine release periods than did the separate HMS and PLGA microspheres. Composite BMP-2/HMS/PLGA microspheres were used to prepare dual-loaded cytokine scaffolds with bone immunomodulatory capacity, which were prepared from composite BMP-2/HMS/PLGA microspheres to increase the osteogenic activity of the dECM and to adsorb interleukin-4 (IL-4) on the surface of the scaffolds. The results showed that the dECM had good cytocompatibility and mechanical strength, and the composite microspheres and IL-4 further endowed the dECM with an ordered spatiotemporally controlled release function, which could release BMP-2 for more than 4 months in the long term and release IL-4 for approximately 10 days in the short term. The composite scaffold not only effectively promoted the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) but also immunomodulated the M1 to M2 polarisation of macrophages (MPs) and mediated the M2 polarisation of MPs, which in turn promoted the osteogenic differentiation of BMSCs, creating a favourable immune microenvironment for bone regeneration. In vivo, the dual drug-loaded scaffolds also exhibited good biocompatibility and significantly superior immunomodulatory bone-enhancing properties compared with those of the other groups. In summary, the combination of dECM scaffolds with cytokine-carrying microspheres and immunomodulatory factors can promote the orderly spatiotemporal release of cytokines, which significantly enhances the bone regeneration and repair effects of dECM scaffolds and is a promising bone filler material for clinical application.
研究领域:
组织工程
·
再生医学
·
生物材料
·
免疫学
·
骨生物学
✓ 已验证
产品关联
DOI
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Yan Xu,Chao Xu,Lei He,Junjie Zhou,Tianwu Chen,Liu Ouyang,Xiaodong Guo,Yanzhen Qu,Zhiqiang Luo,Deyu Duan
Angiogenesis and neurogenesis play irreplaceable roles in bone repair. Although biomaterial implantation that mimics native skeletal tissue is extensively studied, the nerve-vascular network reconstruction is neglected in the design of biomaterials. Our goal here is to establish a periosteum-simulating bilayer hydrogel and explore the efficiency of bone repair via enhancement of angiogenesis and neurogenesis. In this contribution, we designed a bilayer hydrogel platform incorporated with magnesium-ion-modified black phosphorus (BP) nanosheets for promoting neuro-vascularized bone regeneration. Specifically, we incorporated magnesium-ion-modified black phosphorus ( [email protected] ) nanosheets into gelatin methacryloyl (GelMA) hydrogel to prepare the upper hydrogel, whereas the bottom hydrogel was designed as a double-network hydrogel system, consisting of two interpenetrating polymer networks composed of GelMA, PEGDA, and β-TCP nanocrystals. The magnesium ion modification process was developed to enhance BP nanosheet stability and provide a sustained release platform for bioactive ions. Our results demonstrated that the upper layer of hydrogel provided a bionic periosteal structure, which significantly facilitated angiogenesis via induction of endothelial cell migration and presented multiple advantages for the upregulation of nerve-related protein expression in neural stem cells (NSCs). Moreover, the bottom layer of the hydrogel significantly promoted bone marrow mesenchymal stem cells (BMSCs) activity and osteogenic differentiation. We next employed the bilayer hydrogel structure to correct rat skull defects. Based on our radiological and histological examinations, the bilayer hydrogel scaffolds markedly enhanced early vascularization and neurogenesis, which prompted eventual bone regeneration and remodeling. Our current strategy paves way for designing nerve-vascular network biomaterials for bone regeneration.
研究领域:
生物材料
·
组织工程
·
骨再生
·
干细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）