{"title":"An \"inside-out\"-guided genetically engineered hydrogel for augmenting aged bone regeneration","authors":"Yanrun Zhu , Lili Sun , Mingzhuang Hou , Jianfeng Yu , Chenqi Yu , Zihan Zhang , Huilin Yang , Changsheng Liu , Lixin Huang , Dinghua Jiang , Yijian Zhang , Yuan Yuan , Xuesong Zhu","doi":"10.1016/j.bioactmat.2025.05.003","DOIUrl":"10.1016/j.bioactmat.2025.05.003","url":null,"abstract":"<div><div>Senescent bone repair faces significant obstacles due to reduced cellular activity and an unfavorable microenvironment, both of which hinder the osteogenic differentiation of bone marrow-derived stem cells (BMSCs) into osteoblasts (OBs) and subsequent bone formation. Current approaches primarily target senescent cell clearance (senolytics) or suppression of the senescence-associated secretory phenotype (senomorphics), neglecting the complex interactions between BMSCs and the osteogenic microenvironment. In this study, a genetically engineered hydrogel incorporating NAD-dependent deacetylase sirtuins 3 (SIRT3)-loaded nano-vectors and poly (glycerol sebacate)-co-poly (ethylene glycol)/polyacrylic acid (PEGS/PAA) was developed as an “inside-out” strategy for bone regeneration. At the intracellular level, BMSC function is restored, and osteogenesis is promoted through genetically enhanced SIRT3 expression. At the extracellular level, carboxyl functional groups chelate iron ions, simulating a hypoxic environment and promoting synergistic interactions between angiogenesis and osteogenesis. The therapeutic effects of the genetically engineered hydrogel in alleviating senescent damage and enhancing osteogenic differentiation were confirmed in both chemically and naturally induced senescence models <em>in vitro</em>. Local delivery of the hydrogel significantly increased newly formed bone in rat cranial defects. Mechanistically, the central role of SIRT3 in balancing senescence and osteogenesis, as well as its involvement in bone immune signaling pathways, was elucidated through CRISPR/Cas9-mediated editing in mice and transcriptome sequencing. This work presents a novel paradigm that integrates cellular and microenvironmental factors to enhance bone regeneration, offering new hope for treating age-related bone injuries.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"51 ","pages":"Pages 318-332"},"PeriodicalIF":18.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-05-19DOI: 10.1016/j.bioactmat.2025.04.031
Zhenpeng Zhu , Jianming Zhao , Xing Ji , Weimin Hu , Wenyuan Leng , Chunru Xu , Xiaoyu Li , Kunlin Yang , Xuesong Li , Yudong Zheng , Jian Lin
{"title":"Bacterial cellulose-based scaffold with in-situ cationic micelle modification for urethral stricture disease: Sustained drug components release, cytokines recruitment, and bacterial microenvironment regulation","authors":"Zhenpeng Zhu , Jianming Zhao , Xing Ji , Weimin Hu , Wenyuan Leng , Chunru Xu , Xiaoyu Li , Kunlin Yang , Xuesong Li , Yudong Zheng , Jian Lin","doi":"10.1016/j.bioactmat.2025.04.031","DOIUrl":"10.1016/j.bioactmat.2025.04.031","url":null,"abstract":"<div><div>The treatment of urethral stricture disease and the prevention of restenosis present considerable challenges in the field of urology. Tissue-engineered materials, particularly bacterial cellulose scaffolds, have emerged as promising solutions due to their abundant sources, excellent mechanical properties, and biocompatibility. However, for attaining superior treatment for patients with USD, further modification of bacterial cellulose is necessary. We have fabricated a dual-network scaffold with enhanced antibacterial properties and cytokines absorption ability through in-situ polymerization of cationic polyurethane micelles and cyclodextrin on oxidized bacterial cellulose. This scaffold also enables long-term sustained release of loaded drug components. Animal model studies have confirmed that this scaffold can achieve urethral repair outcomes comparable to those of normal urethral tissue. This innovative material provides a robust foundation for advancing new concepts and methodologies in the treatment of urethral stricture disease, potentially transforming clinical approaches to this challenging condition.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"51 ","pages":"Pages 306-317"},"PeriodicalIF":18.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-05-19DOI: 10.1016/j.bioactmat.2025.05.004
Shishuo Li , Zhentao Man , Kangqing Zuo , Linbo Zhang , Taixing Zhang , Guiyong Xiao , Yupeng Lu , Wei Li , Ningbo Li
{"title":"Advancement in smart bone implants: the latest multifunctional strategies and synergistic mechanisms for tissue repair and regeneration","authors":"Shishuo Li , Zhentao Man , Kangqing Zuo , Linbo Zhang , Taixing Zhang , Guiyong Xiao , Yupeng Lu , Wei Li , Ningbo Li","doi":"10.1016/j.bioactmat.2025.05.004","DOIUrl":"10.1016/j.bioactmat.2025.05.004","url":null,"abstract":"<div><div>Artificial implants have consistently been recognized as the most effective clinical strategy for repairing bone fractures and defects, particularly in orthopedics and stomatology. Nowadays, the focus of bone repair has shifted from basic fixation and structural restoration to the reconstruction of multifunctional “live” tissue to mimic the natural bone microenvironment. However, developing the smart implants with ideal osteogenesis-related multi-functions remains challenging, as the effects of physicochemical properties of implant materials on intracellular signaling, stem cell niches, and tissue regeneration are not yet fully understood. Herein, we systematically explore recent advancements in innovative strategies for bone repair and regeneration, revealing the significance of the smart implants that closely mimic the natural structure and function of bone tissue. Adaptation to patient-oriented osteogenic microenvironments, dynamic osteoblastogenesis-osteoclastogenesis balance, antibacterial/bactericidal capacity, vascularization, and osteoimmunomodulatory capacity and their regulatory mechanisms achieved by biomaterials design and functional modifications are thoroughly summarized and analyzed. Notably, the popular research on multifunctional platforms with synergetic interactions between different functions and treatment of complex clinical issues, including the emerging neurogenic bone repair, is also significantly discussed for developing more intelligent implants. By summarizing recent research efforts, this review proposes the latest multifunctional strategies and synergistic mechanisms of smart bone implants, aiming to provide better bone defect repair applications that more closely mimic the natural bone tissue.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"51 ","pages":"Pages 333-382"},"PeriodicalIF":18.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-05-16DOI: 10.1016/j.bioactmat.2025.05.005
Jiyu Hyun , Junhyeung Park , Jihun Song , Chaerim Yoo , Seonmi Jang , Sang Yoon Lee , Jiseon An , Hyun Su Park , Seunghyuk Jung , Dasom Kong , Ji Hyeon Cho , Tae Il Lee , Ki Dong Park , Gwang-Bum Im , Jee-Heon Jeong , Hyun-Ji Park , Dong Yun Lee , Suk Ho Bhang
{"title":"Subaqueous acoustic pressure system based one day heterotypic pseudo-islet spheroid formation with adipose derived stem cells for graft survival-related function enhancement","authors":"Jiyu Hyun , Junhyeung Park , Jihun Song , Chaerim Yoo , Seonmi Jang , Sang Yoon Lee , Jiseon An , Hyun Su Park , Seunghyuk Jung , Dasom Kong , Ji Hyeon Cho , Tae Il Lee , Ki Dong Park , Gwang-Bum Im , Jee-Heon Jeong , Hyun-Ji Park , Dong Yun Lee , Suk Ho Bhang","doi":"10.1016/j.bioactmat.2025.05.005","DOIUrl":"10.1016/j.bioactmat.2025.05.005","url":null,"abstract":"<div><div>To overcome Type 1 diabetes mellitus (T1DM), which can cause hyperglycemia due to diminished insulin secretion of β-cell function, islet transplantation has been developed with various strategies including pseudo-islet. However, conventional pseudo-islet formation techniques combining with other cells depend on natural cellular aggregation, which requires at least 5 days to form and even show segregation of distinct cell types, leading to diminished cell viability and function. Herein, we applied a subaqueous free-standing 3D cell culture (FS) device, which can reduce the spheroid formation time by trapped cell in nodes of acoustic standing wave. Briefly, Culturing with adipose-derived stem cells (ADSCs) to form heterotypic pseudo-islet (Hislet) in FS device dramatically reduced formation time less than one day. Hislet demonstrated enhancement of cell viability than conventional pseudo-islet formation method. Additionally, ADSCs combined Hislet proved strong secretion of various paracrine factors. Also results showed significantly increased angiogenesis effect and immunomodulation effect for various type of immune cells in Hislet compared to islet, which can enhance transplantation survival. Furthermore, Hislet validated glucose-regulating capacity and enhanced angiogenesis effect <em>in vivo</em> T1DM model. Throughout this study, we propose a novel strategy for forming Hislet that can overcome the limitations of conventional Islet and pseudo-islet for T1DM.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"51 ","pages":"Pages 276-292"},"PeriodicalIF":18.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-05-16DOI: 10.1016/j.bioactmat.2025.05.013
Bo Tian , Heng Wang , Yue Zhang , Jinmin Lv , Dongxiao Li , Chenmeng Zhou , Jialu Xu , Yichao Ni , Bingbing Wu , Mingchao Zhang , Huaxing Dai , Fang Xu , Jinyu Bai , Chao Wang , Xiaozhong Zhou
{"title":"Tryptophan-producing bacteria to mitigate osteoporosis and intestinal dysfunction","authors":"Bo Tian , Heng Wang , Yue Zhang , Jinmin Lv , Dongxiao Li , Chenmeng Zhou , Jialu Xu , Yichao Ni , Bingbing Wu , Mingchao Zhang , Huaxing Dai , Fang Xu , Jinyu Bai , Chao Wang , Xiaozhong Zhou","doi":"10.1016/j.bioactmat.2025.05.013","DOIUrl":"10.1016/j.bioactmat.2025.05.013","url":null,"abstract":"<div><div>The relationship between gut microbiota and host health and disease is intricate, with microbiota-derived metabolites playing a crucial role in the gut-organ axis. In this study, we observe significantly decreased levels of microbial metabolites, particularly tryptophan derivatives in osteoporosis mice. Loss of tryptophan induced intestinal epithelial barrier dysfunction which compromised intestinal barrier integrity, leading to bone inflammatory responses and pathological osteoporosis. Through supplementation of tryptophan-producing bacteria, we effectively repair damaged intestinal barriers in colitis mice and mitigate bone loss, indicating the link between chronic colitis and osteoporosis. This approach offers a promising synthetic biology-based strategy to improve osteoporosis therapy by targeting gut tryptophan. This intervention also alleviates age-related osteoporosis in an aged mouse model, providing a potential therapeutic avenue for combating osteoporosis, a disease of growing concern in aging populations.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"51 ","pages":"Pages 293-305"},"PeriodicalIF":18.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-05-14DOI: 10.1016/j.bioactmat.2025.04.028
Wenqiang Lou , Xinzhu Qiu , Yiming Qin , Yingnan Lu , Yong Cao , Hongbin Lu
{"title":"3D-printed advanced scaffold armed with exosomes derived from human skeletal stem cell identified by single-cell RNA sequencing enhances osteochondral regeneration","authors":"Wenqiang Lou , Xinzhu Qiu , Yiming Qin , Yingnan Lu , Yong Cao , Hongbin Lu","doi":"10.1016/j.bioactmat.2025.04.028","DOIUrl":"10.1016/j.bioactmat.2025.04.028","url":null,"abstract":"<div><div>Osteochondral defects (OCDs) pose a significant clinical challenge due to their limited self-repair capacity. The complex structure and distinct biological properties of articular cartilage and subchondral bone further complicate regeneration.In this study, we introduce a novel osteochondral regeneration strategy leveraging single-cell RNA sequencing (ScRNA-seq) to identify a unique population of skeletal stem cells (SSCs) derived from the infrapatellar fat pad (IFP). These SSCs exhibit high differentiation potential and robust chondrogenic capacity. Using flow cytometry, we isolated SSCs and extracted their exosomes (Exos), which were subsequently combined with hydrogels to develop a novel bioink. Employing 3D printing technology, we fabricated an innovative hydrogel scaffold designed to adapted to the defective areas enhance OCD repair.In a rat OCD model, the 3D-printed hydrogel scaffold loaded with SSC-derived Exos (SSC-Exos) demonstrated exceptional osteochondral regeneration, facilitating synchronous repair of both cartilage and subchondral bone. <em>In vitro</em> experiments revealed that SSC-Exos significantly enhanced the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Importantly, SSC-Exos derived from the IFP exhibited superior cartilage regeneration capabilities compared to Exos from adipose-derived mesenchymal stem cells (ADSC-Exos). High-throughput sequencing further elucidated the critical role of the microRNA-214-3p (miR-214-3p)/jagged canonical Notch ligand 2 (JAG2) axis in SSC-Exos-mediated cartilage regeneration. Collectively, the 3D-printed hydrogel scaffold loaded with SSC-Exos represents an innovative and effective strategy for OCD repair, with potential for clinical translation.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"51 ","pages":"Pages 231-256"},"PeriodicalIF":18.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-05-14DOI: 10.1016/j.bioactmat.2025.05.007
Siqi Zhang , Hannan Cui , Jing Wang , Jie Zhou , Hongli Chen , Xinli Wang , Qian Yang , Jiahao Cao , Kaili Hao , Shanshan Fu , Wuyang Zhang , Xu Wang , Xinsen Lin , Xiqing Sun , Wei Lei , Tengjiao Wang , Yafei Feng
{"title":"HydroWrap for T2DM-Related Fractures: A smart H2S-delivery controller modulating Macrophage senescence","authors":"Siqi Zhang , Hannan Cui , Jing Wang , Jie Zhou , Hongli Chen , Xinli Wang , Qian Yang , Jiahao Cao , Kaili Hao , Shanshan Fu , Wuyang Zhang , Xu Wang , Xinsen Lin , Xiqing Sun , Wei Lei , Tengjiao Wang , Yafei Feng","doi":"10.1016/j.bioactmat.2025.05.007","DOIUrl":"10.1016/j.bioactmat.2025.05.007","url":null,"abstract":"<div><div>Impaired fracture healing in type 2 diabetes mellitus (T2DM) poses a significant clinical challenge, primarily due to a compromised bone microenvironment driven by senescent macrophages and their amplifying effects. Reduced hydrogen sulfide (H<sub>2</sub>S) levels are a critical contributor to this pathology. To address this, we developed HydroWrap, an advanced H<sub>2</sub>S-delivery controller designed to modulate distinct stages of macrophage senescence. Under near-infrared (NIR) irradiation, HydroWrap underwent an increase in temperature, causing the hydrogel network to contract and accelerate H<sub>2</sub>S generation. This rapid delivery restores H<sub>2</sub>S levels, alleviating mitochondrial dysfunction and suppressing senescence-associated secretory phenotypes (SASP), thereby interrupting the senescence cascade. In T2DM's hyperglycemic bone microenvironment, HydroWrap provides sustained, glucose-responsive H<sub>2</sub>S release, promoting mitophagy and preventing macrophage senescence progression. This dual mechanism addresses both acute and chronic dysfunctions associated with senescence. <em>In vivo</em> studies demonstrated that HydroWrap significantly improved fracture healing by reducing recovery time and enhancing bone quality. These findings underscore the therapeutic potential of modulating macrophage senescence in T2DM using a biocompatible drug delivery system. HydroWrap offers a promising strategy for improving fracture outcomes in diabetic patients and may hold broader applications in senescence-related diseases.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"51 ","pages":"Pages 257-273"},"PeriodicalIF":18.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-05-13DOI: 10.1016/j.bioactmat.2025.05.010
Ming Yan , Baixue Xiao , Anthony Yosick , Bei Liu , Hani A. Awad
{"title":"Dose-dependent osteoimmunomodulatory effects of amorphous calcium phosphate nanoparticles promote 3D-printed scaffold-mediated bone regeneration","authors":"Ming Yan , Baixue Xiao , Anthony Yosick , Bei Liu , Hani A. Awad","doi":"10.1016/j.bioactmat.2025.05.010","DOIUrl":"10.1016/j.bioactmat.2025.05.010","url":null,"abstract":"<div><div>Regenerating critical-sized long bone defects poses substantial challenges due to limitations of autografts and processed allografts. Biomaterial scaffolds offer versatile alternatives, yet their effectiveness is often constrained by their limited innate osteoinductivity. While growth factors and cells can enhance osteoinduction, the inclusion of biologics in biomaterial scaffolds creates regulatory challenges for clinical translation. To address this, here we describe three-dimensional (3D) printed polycaprolactone (PCL) scaffolds for temporally controlled delivery of osteoimmunomodulatory amorphous calcium phosphate-chitosan nanoparticles (ACPC-NP). <em>In vitro</em>, the ACPC-NP exhibit concentration dependent effects on osteoblasts, monocytes, and osteoclasts. At increasing concentrations up to 500 μg/ml, these nanoparticles stimulate osteogenesis, modulate M2/M1 macrophage polarization, and inhibit osteoclast maturation and activity. Leveraging these concentration-dependent effects <em>in vivo</em> through temporally controlled release of ACPC-NP from 3D-printed PCL scaffolds, we observe the complete regeneration and the restoration of biomechanical strength of critically sized radial defects in rats. Such healing is absent in defects implanted with bare PCL scaffolds or those loaded with calcium-phosphate microparticles. The tunable osteoimmunomodulation by the NP underscores the translational potential of this technology to yield structurally sound and functionally robust bone regeneration outcomes.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"51 ","pages":"Pages 197-210"},"PeriodicalIF":18.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2025-05-13DOI: 10.1016/j.bioactmat.2025.05.008
Shue Jin , Yongrui Cai , Yaxing Li , Jing Wen , Xiaoxue Fu , Ping Song , Pengyu Lu , Anjing Chen , Zeyu Luo , Weinan Zeng , Jidong Li , Zongke Zhou
{"title":"A sandwich-like nanofibrous scaffold with macrophage phenotype transformation and myogenic differentiation for skeletal muscle regeneration","authors":"Shue Jin , Yongrui Cai , Yaxing Li , Jing Wen , Xiaoxue Fu , Ping Song , Pengyu Lu , Anjing Chen , Zeyu Luo , Weinan Zeng , Jidong Li , Zongke Zhou","doi":"10.1016/j.bioactmat.2025.05.008","DOIUrl":"10.1016/j.bioactmat.2025.05.008","url":null,"abstract":"<div><div>Skeletal muscle injuries caused by trauma, infections, or sports tear are common clinical diseases. Currently, the regeneration and repair of muscle tissue, which is highly heterogeneous, remains a significant challenge. Given the anisotropic structure, high strength and tensile characteristics of skeletal muscle, this study proposes a treatment strategy for muscle injury that combines materials nano-topological cues and biochemical cues. The approach aims to facilitate muscle injury repair through the use of heterogeneous nanofibers on the surface of the sandwich-like electrospun nanofibrous scaffold and macrophage phenotype transformation. Specifically, the outer layer of the sandwich-like scaffold consists of highly aligned fibers, while the middle layer is a core-shell structured random fibers containing hyaluronic acid, and the fiber matrix is composed of optimized proportions of polycaprolactone and gelatin. Mechanical testing shows that the sandwich-like scaffold combines the excellent tensile strength of the outer aligned fibers with the larger elongation at break and suture retention strength of the inner random fibers. Cell and animal experiments confirmed that the aligned fibers in the outer layers guide the cell adhesion, cytoskeleton and nuclear remodeling, and myogenic differentiation of myoblasts, and hyaluronic acid promotes both myogenic differentiation and macrophage phenotype transformation, ultimately accelerating skeletal muscle regeneration. This sandwich-like nanofibrous scaffold provides a novel cell-free, and factor-free approach for the regeneration of skeletal muscle injuries.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"51 ","pages":"Pages 211-230"},"PeriodicalIF":18.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}