Acta Biomaterialia
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2026
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IF 10.4
Lin Zhu,Zixin Gao,Xinyi Chen,Qiang Zhang,Jinsheng Hua,Wenxiang Fang,Yingying Zhang,Yanfei Feng,Xiufang Li,Renchuan You
The microenvironment within hydrogels is essential for tissue regeneration and cell colonization, yet it presents a significant obstacle to the development of injectable hydrogel biomaterials. Hyaluronic acid (HA) has garnered substantial interest in injectable therapeutic applications. However, it is confronted with the obstacles of lacking an ECM-mimicking structure and a compromise between mechanical properties and injectability. In this study, we develop an in situ forming injectable ECM-mimicking hydrogel that concurrently replicates structural proteins and glycosaminoglycans by combining with nanofibrillated silks (nanosilks) containing RGD tripeptide with Tyramine-modified HA (HA-Tyr). The precursor solution exhibits favorable injectability (extrusion force < 2 N) and undergoes rapid in situ gelation, ensuring that it conforms precisely to the tissue defect. Through covalent interfacial crosslinking, the nanosilk network simultaneously enhances mechanical strength, elastic recovery, and enzymatic resistance, thereby resolving the challenging trade-off among these properties. Moreover, the incorporated nanosilks provide critical cues for improving the proliferation and long-term survival of encapsulated stem cells in vitro . Following subcutaneous implantation, the HA-Tyr/nanosilks hydrogels exhibit good biocompatibility, structural retention, and the ability to support cell survival and host tissue integration. This study presents a bioactive and cell-instructive injectable material, thereby expanding the potential of stem cell-based minimally invasive therapies. Statement of significance Injectable hydrogels encounter two significant obstacles. One of the challenges is the inability to create appropriate microenvironments that support pertinent biological and structural functions. The second issue is the challenge of reconciling the conflict between injectability and mechanical properties. This work develops a silk nanoengineering strategy to construct an in situ forming injectable hydrogel that mimics the native ECM. By integrating nanosilks containing RGD with tyramine-modified hyaluronic acid, this composite concurrently replicates both structural proteins and glycosaminoglycans. This design eliminates the conventional trade-offs between enzymatic stability, elastic recovery, mechanical strength, and injectability. This injectable hydrogel offers an effective strategy for minimally invasive therapies in soft tissue repair. Download: Download high-res image (268KB) Download: Download full-size image
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2021
·Vol. 19
·期 1
·1-15
·
IF 10.435
Li Yan,Wang Juan,Qian Dejian,Chen Liang,Mo Xiumei,Wang Lei,Wang Yan,Cui Wenguo
Background Most of the natural extracellular matrix (ECM) is a three-dimensional (3D) network structure of micro/nanofibers for cell adhesion and growth of 3D. Electrospun fibers distinctive mimicked 2D ECM, however, it is impossible to simulate 3D ECM because of longitudinal collapse of continuous micro/nanofibers. Herein, 3D electrospun micro/nano-fibrous sponge was fabricated via electrospinning, homogenization, shaping and thermal crosslinking for 3D tissue regeneration of cells and vascular. Results Fibrous sponge exhibited high porosity, water absorption and compression resilience and no chemical crosslinked agent was used in preparation process. In vitro studies showed that the 3D short fiber sponge provided an oxygen-rich environment for cell growth, which was conducive to the 3D proliferation and growth of HUVECs, stimulated the expression of VEGF, and well promoted the vascularization of HUVECs. In vivo studies showed that the 3D short fiber sponges had a good 3D adhesion to the chronic wound of diabetes in rats. Furthermore, 3D short fibrous sponges were better than 2D micro/nanofiber membranes in promoting the repair of diabetic full-thickness skin defects including wound healing, hair follicle regeneration, angiogenesis, collagen secretion. Conclusion Therefore, electrospun short fibrous sponges are special candidates for mimicking the 3D ECM and promoting 3D regeneration of tissue. Graphic Abstract
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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细胞生物学
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高影响因子
Materials
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2020
·Vol. 13
·期 22
·5277
·
IF 3.057
Kai Li,Yuting Zhu,Qiang Zhang,Xiaoli Shi,Feng Liang,Dong Han
Although there have been many studies on using hydrogels as substitutes for natural extracellular matrices (ECMs), hydrogels that mimic the structure and properties of ECM remain a contentious topic in current research. Herein, a hierarchical biomimetic fiber hydrogel was prepared using a simple strategy, with a structure highly similar to that of the ECM. Cell viability experiments showed that the hydrogel not only has good biocompatibility but also promotes cell proliferation and growth. It was also observed that cells adhere to the fibers in the hydrogel, mimicking the state of cells in the ECM. Lastly, through a rat skin wound repair experiment, we demonstrated that this hydrogel has a good effect on promoting rat skin healing. Its high structural similarity to the ECM and good biocompatibility make this hydrogel a good candidate for prospective applications in the field of tissue engineering.Keywords:hydrogel;hierarchy;fiber;self‑healing;wound dressing
研究领域:
生物材料
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组织工程
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伤口愈合
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PubMed
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Materials Today Bio
·
2024
·
IF 8.7
Shuang Liu,Julia Simińska-Stanny,Lizhao Yan,Lihong Fan,Xiaoyue Ding,Tengda Ma,Wei Guo,Yingsong Zhao,Ming Li,Jianghai Chen,Oseweuba Valentine Okoro,Armin Shavandi,Lei Nie
Extensive research efforts are being directed towards identifying alternatives to autografts for the treatment of peripheral nerve injuries (PNIs) with engineered nerve conduits (NGCs) identified as having potential for PNI patients. These NGCs, however, may not fulfill the necessary criteria for a successful transplant, such as sufficient mechanical structural support and functionalization. To address the aforementioned limitations of NGCs, the present investigation explored the development of double cross-linked hydrogels (o-CSMA-E) that integrate the biocompatibility of porcine tendon extracellular matrix (ECM) with the antimicrobial and conductive properties of methacrylated quaternary chitosan. The hydrogels had matrices that could promote the growth of axons and the transmission of neural signals. The hydrogels were subsequently incorporated into a nanofibrous PLLA-ZnO sheath scaffold (ZnO@PLLA) to emulate the natural nerve structure, guiding cell growth and facilitating nerve regeneration. The collaboration of core and sheath materials in ZnO@PLLA/o-CSMA-E nerve guidance conduits resulted in enhanced migration of Schwann cells, formation of myelin sheaths, and improved locomotion performance in rats with sciatic nerve defects when in vivo studies were undertaken. Notably, the in vivo studies demonstrated the similarity between the newly developed engineered NGCs and autologous transplants, with the newly engineered NGCs possessing the potential to promote functional recovery by mimicking the tubular structure and ECM of nerves.
研究领域:
生物医学工程
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神经科学
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组织工程
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高影响因子
Science Advances
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2020
·Vol. 6
·期 48
·
IF 13.117
Yun Xu,Guodong Shi,Jincheng Tang,Ruoyu Cheng,Xiaofeng Shen,Yong Gu,Liang Wu,Kun Xi,Yihong Zhao,Wenguo Cui,Liang Chen
Current homogeneous bioscaffolds could hardly recapture the regenerative microenvironment of extracellular matrix. Inspired by the peculiar nature of dura matter, we developed an extracellular matrix–mimicking scaffold with biomimetic heterogeneous features so as to fit the multiple needs in dura mater repairing. The inner surface endowed with anisotropic topology and optimized chemical cues could orchestrate the elongation and bipolarization of fibroblasts and preserve the quiescent phenotype of fibroblasts indicated by down-regulated α–smooth muscle actin expression. The outer surface could suppress the fibrotic activity of myofibroblasts via increased microfiber density. Furthermore, integrin β1 and Yes-associated protein molecule signaling activities triggered by topological and chemical cues were verified, providing evidence for a potential mechanism. The capability of the scaffold in simultaneously promoting dura regeneration and inhibiting epidural fibrosis was further verified in a rabbit laminectomy model. Hence, the so-produced heterogeneous fibrous scaffold could reproduce the microstructure and function of natural dura.
研究领域:
生物材料学
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再生医学
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细胞生物学
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高影响因子
Advanced Healthcare Materials
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2026
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IF 11
Ziheng Wei,Fen Tang,Wenda Xu,Yongzhi Cui,Songyan Gao,Qingjie Kong,Si Chen,Xiongsheng Chen
Osteoporotic fractures pose a significant clinical challenge in aging societies due to the limited efficacy and high re-fracture risk associated with conventional treatments. To address this, we developed EXOs@ECM-SCS, a multifunctional bioactive hydrogel that encapsulates exosomes derived from induced pluripotent stem cell-induced mesenchymal stem cells within a hybrid matrix of decellularized extracellular matrix and methacrylated sulfated chitosan. This composite system promotes bone regeneration through a synergistic strategy that concurrently targets angiogenesis, immunomodulation, neurogenesis, and osteogenesis (AINO). Experimental results demonstrated that EXOs@ECM-SCS significantly enhanced osteogenic differentiation, angiogenic activity, and neural regeneration, while also driving macrophage polarization toward the M2 phenotype. These multifaceted effects collectively improved bone mass accumulation, mineralization, and fracture healing in an osteoporotic mouse model. Mechanistic insights from exosomal sequencing highlighted the involvement of key miRNAs such as miR-100-5p and miR-320a-3p, along with PI3K-Akt and MAPK signaling pathways. These findings underscore EXOs@ECM-SCS as an innovative therapeutic platform that leverages coordinated multimodal regulation to accelerate osteoporotic fracture repair.
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ACS Applied Materials & Interfaces
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2024
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IF 8.3
Hengyi Lin,Enhuai Weng,Xin Rong,Li Yu,Yiling Chen,Yukun Jiang,Haikun Hu,Zhenming Wang,Shujuan Zou,Zhiai Hu
Regenerating periodontal defects in osteoporosis patients presents a significant clinical challenge. Unlike the relatively straightforward regeneration of homogeneous bone tissue, periodontal regeneration requires the intricate reconstruction of the cementum–periodontal ligament–alveolar bone interface. Strontium (Sr)-doped biomaterials have been extensively utilized in bone tissue engineering due to their remarkable pro-osteogenic attributes. However, their application in periodontal tissue regeneration has been scarcely explored. In this study, we synthesized an innovative injectable Sr-BGN/GNM scaffold by integrating Sr-doped bioactive glass nanospheres (Sr-BGNs) into the nanofiber architecture of gelatin nanofiber microspheres (GNMs). This design, mimicking the natural bone extracellular matrix (ECM), enhanced the scaffold’s mechanical properties and effectively controlled the sustained release of Sr ions (Sr2+), thereby promoting the proliferation, osteogenic differentiation, and ECM secretion of PDLSCs and BMSCs, as well as enhancing vascularization in endothelial cells. In vivo experiments further indicated that the Sr-BGNs/GNMs significantly promoted osteogenesis and angiogenesis. Moreover, the scaffold’s tunable degradation kinetics optimized the prolonged release and pro-regenerative effects of Sr2+ in vivo, matching the pace of periodontal regeneration and thereby facilitating the regeneration of functional periodontal tissues under osteoporotic conditions. Therefore, Sr-BGNs/GNMs emerge as a promising candidate for advancing periodontal regeneration strategies.
研究领域:
口腔医学
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生物材料学
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组织工程学
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PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2026
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IF 5.8
Yanxing Lan,Zijun Xu,Yajing Li,Dahe Liu,Wenguang Lu,Zhangwei Li,Peier Chen,Guoqin Chen
Impaired microcirculation and insufficient angiogenesis critically limit functional recovery after myocardial infarction (MI), yet effective strategies for localized and sustained vascular regeneration remain lacking. Here, we develop a heart-specific extracellular matrix–based hydrogel for the intrapericardial delivery of Astragaloside IV (AS-IV), a pro-angiogenic bioactive monomer derived from traditional Chinese medicine. The bioactive hydrogel is fabricated from decellularized porcine heart extracellular matrix (HdECM), which provides a biomimetic cardiac microenvironment while enabling sustained local release of AS-IV. Distinct from conventional intramyocardial injection, intrapericardial administration allows the hydrogel to form a patch-like depot on the cardiac surface, achieving prolonged cardiac retention with minimal tissue injury. Under oxygen–glucose deprivation, the AS-IV@HdECM hydrogel synergistically enhances endothelial cell survival, migration, and angiogenic capacity while suppressing apoptosis. In a rat MI model, localized delivery of AS-IV via HdECM markedly promotes neovascularization, attenuates myocardial fibrosis, reduces cardiomyocyte apoptosis, and significantly improves cardiac function. Mechanistically, integrative proteomic and network pharmacology analyses, together with experimental validation, indicate that the therapeutic effects are associated with activation of the EGFR/Raf–MEK–ERK signaling pathway. This work establishes a localized therapeutic paradigm that integrates heart-specific matrix cues with traditional Chinese medicine, offering a translational biomaterials strategy for microvascular regeneration and cardiac repair after MI.
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Stem Cell Research & Therapy
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2021
·Vol. 12
·期 1
·1-14
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IF 6.832
Zhang Jiayu,Lan Tingting,Han Xue,Xu Yuchan,Liao Li,Xie Li,Yang Bo,Tian Weidong,Guo Weihua
Background The low survival rate or dysfunction of extracellular matrix (ECM)-based engineered organs caused by the adverse effects of unfavourable local microenvironments on seed cell viability and stemness, especially the effects of excessive reactive oxygen species (ROS), prompted us to examine the importance of controlling oxidative damage for tissue transplantation and regeneration. We sought to improve the tolerance of seed cells to the transplant microenvironment via antioxidant pathways, thus promoting transplant efficiency and achieving better tissue regeneration. Methods We improved the antioxidative properties of ECM-based bioroots with higher glutathione contents in dental follicle stem cells (DFCs) by pretreating cells or loading scaffolds with the antioxidant NAC. Additionally, we developed an in situ rat alveolar fossa implantation model to evaluate the long-term therapeutic effects of NAC in bioroot transplantation. Results The results showed that NAC decreased H 2 O 2 -induced cellular damage and maintained the differentiation potential of DFCs. The transplantation experiments further verified that NAC protected the biological properties of DFCs by repressing replacement resorption or ankylosis, thus facilitating bioroot regeneration. Conclusions The following findings suggest that NAC could significantly protect stem cell viability and stemness during oxidative stress and exert better and prolonged effects in bioroot intragrafts.
研究领域:
组织工程
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干细胞生物学
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牙科科学
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再生医学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Lin Li,Kun Liu,Jingsheng Chen,Wei Wen,Hong Li,Lihua Li,Shan Ding,Mingxian Liu,Changren Zhou,Binghong Luo
As a particular cell niche, natural bone extracellular matrix (ECM) is an organic-inorganic composite material formed by mineralization of liquid crystal (LC) collagen fiber network. However, designing bone repair materials that highly imitate the LC characteristic and composite components of natural bone ECM is a great challenge. Here, we report a novel kind of bone ECM-inspired biomineralization chitin whisker LC hydrogels. First, photocurable chitin whisker LC hydrogels with bone ECM-like chiral nematic LC state and viscoelasticity are created. Next, biomineralization, guided by LC hydrogels, is carried out to truly mimic the mineralization process of natural bone, so as to obtain the organic-inorganic composite materials with bone ECM-like microenvironment. The chitin whisker LC hydrogels exhibit superior biomineralization, protein adsorption and osteogenesis ability, more importantly, LC hydrogel with negatively charged –COOH groups is more conducive to biomineralization and shows more desirable osteogenic activity than that with positively charged –NH 2 groups. Notably, compared with the pristine LC hydrogels, the biomineralization LC hydrogels display more favorable osteogenesis ability due to their bone ECM-like LC texture and bone-like hydroxyapatite. This study opens an avenue toward the design of bone ECM-inspired biomineralization chitin whisker LC hydrogels for bone regeneration.
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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材料科学
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再生医学
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Jiaye Li,Fengyuan Wang,Youjun Ding,Guopu Chen,Qian Tan,Yuanjin Zhao
Adipose-derived stem cells (ADSCs) have proven to be valuable in chronic wounds treatment, while their applications often suffer from low survival rates in complex wound environments. Here, we developed a novel biomimetic extracellular matrix (ECM)-like chondroitin sulfate (ChS) hydrogel loaded with ADSCs and polydopamine nanoparticles (PDA NPs) to accelerate chronic wound healing. We have demonstrated that the ChS-based hydrogel could mimick ECM, promoting cell proliferation and migration, and the PDA NPs exhibited antioxidative and antibacterial effects. Thus, the hybrid hydrogel was identified to promote diabetic wound healing by supporting ADSCs’ survival, enhancing angiogenesis, re-epithelialization, and reducing inflammation. These results indicated that our proposed ADSCs and PDA integrated biomimetic ECM-like hydrogel had practical significance in treating chronic wounds and different clinical diseases.
研究领域:
生物材料学
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再生医学
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组织工程
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高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 8
·2877-2885
·
IF 6.6
Tengling Wu,Luxing Liu,Ziwei Gao,Chunyan Cui,Chuanchuan Fan,Yang Liu,Mingyuan Di,Qiang Yang,Ziyang Xu,Wenguang Liu
It has always been a huge challenge to construct high-strength hydrogels that are composed entirely of natural polymers. In this study, inspired by the structural characteristics of the extracellular matrix (ECM), gelatin and hydrazide alginate were employed to mimic the composition of collagen and glycosaminoglycans (GAGs) in the ECM, respectively, to develop natural polymer (NP) high-strength hydrogels crosslinked by physical and covalent interactions (Gelatin-HAlg-DN). First, HAlg and gelatin can form physically crosslinked hydrogels (Gelatin-HAlg) due to electrostatic and hydrogen bond interactions. Then, the Gelatin-HAlg hydrogels can be further covalently crosslinked in the presence of 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to obtain Gelatin-HAlg-DN hydrogels. The obtained Gelatin-HAlg-DN hydrogels exhibit considerably enhanced mechanical properties (tensile strength: 0.9 MPa; elongation at break: 177%) with a maximum 16- and 3.2-fold increase in tensile strength and elongation at break, respectively, compared with gelatin methacrylate (GelMA) hydrogels. Importantly, the Gelatin-HAlg-DN hydrogels exhibit excellent biodegradability and swelling stability under physiological conditions, and the capability to support cell adhesion and proliferation. In a rat critical size bone defect model, Gelatin-HAlg-DN hydrogels loaded with psoralen could effectively promote bone regeneration, showing appealing potential as tissue engineering scaffolds.
研究领域:
生物材料学
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组织工程学
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再生医学
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PubMed
高影响因子
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