National Science Review
·
2024
·
IF 16.3
Qiu Peng-Fei,Qiang Lei,Kong Weiqing,Wang Fang-Zhou,Wang Hong-Qin,Hou Ke-Xin,Liu Yihao,Li Cheng-Hui,Zheng Pengfei
The escalating prevalence of skeletal muscle disorders highlights the critical need for innovative treatments for severe injuries like volumetric muscle loss. Traditional treatments, such as autologous transplants, are constrained by limited availability and current scaffolds often fail to meet complex clinical needs. This study introduces a new approach to VML treatment using a shape memory polymer (SMP) based on block copolymers of perfluoropolyether and polycaprolactone diol. This SMP mimics the biomechanical properties of natural muscle, exhibiting a low elastic modulus (2–6 MPa), high tensile strength (72.67 ± 3.19 MPa), exceptional toughness (742.02 ± 23.98 MJ m−3), and superior biocompatibility, thereby enhancing skeletal muscle tissue integration and regeneration within 4 weeks. Moreover, the polymer's shape memory behavior and ability to lift over 5000 times its weight showcase significant potential in both severe muscle disorder treatment and prosthetic applications, surpassing existing scaffold technologies. This advancement marks a pivotal step in the development of artificial muscles for clinical use.
研究领域:
生物医学工程
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材料科学
·
组织工程
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Xinting Feng,Zhiwen Luo,Wei Zhang,Renwen Wan,Yisheng Chen,Fangqi Li,Yanwei He,Zhiheng Lin,James Hoipo Hui,João Conde,Shiyi Chen,Zhijie Zhao,Xianwen Wang
Volumetric muscle loss (VML) is a severe condition in which the loss of skeletal muscle surpasses the body's intrinsic repair capabilities, leading to irreversible functional deficits and potential disability, with persistent inflammation and impaired myogenic differentiation. To address these challenges, a novel zinc-dihydromyricetin (Zn-DHM) nanozyme with superoxide dismutase (SOD)-like activity is developed, designed to neutralize excessive reactive oxygen species (ROS) and restore oxidative balance. Zn-DHM mitigates oxidative stress and promotes polarization of macrophages from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype, thereby reducing chronic inflammation and creating a conducive environment for muscle repair. Further, Zn-DHM significantly enhances the myogenic differentiation of C 2 C 12 cells, accelerating wound healing processes. These studies confirm the biosafety and low toxicity of Zn-DHM. As per a murine tibialis anterior VML model, Zn-DHM effectively suppresses inflammation and markedly improves skeletal muscle repair outcomes. Single-cell RNA sequencing reveals that Zn-DHM treatment increases the expression of M2 macrophage markers and enhances the proliferation and differentiation capacity of muscle stem cells (MuSCs). In addition, intercellular communication analysis reveals interactions between MuSCs and macrophages in the Zn-DHM treatment group, suggesting that these interactions may drive tissue regeneration through the activation of the GAS and Notch signaling pathways.
研究领域:
生物医学工程
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分子生物学
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免疫学
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产品关联
DOI
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-21
·
IF 15.7
Fang Wenzhuo,Du Xuan,Yang Ranxing,Liu Meng,Yang Ming,Jin Yangwang,Gao Guo,Fu Qiang,Wang Ying
Stress urinary incontinence (SUI) remains a significant clinical challenge due to the lack of strategies that simultaneously address muscle degeneration, neurogenic atrophy, and vascular deficits. Here, we report an innovative injectable system that combines a thermo-responsive poly(N-isopropylacrylamide)-COOH/leucine/decellularized extracellular matrix hydrogel with adipose-derived stem cells (ADSCs) pre-programmed by zeolitic imidazolate framework-8/polyethylene glycol 200@magnesium (ZIF-8/PEG200@Mg) nanoparticles. In vitro, programmed ADSCs exhibit enhanced neurogenic differentiation, while the hydrogels support robust myogenic activity and cell viability. In a female rat model of SUI—chosen to reflect the higher prevalence of SUI in women—the composite system leads to a marked improvement in leak point pressure (LPP) and restores urethral sphincter function. Mechanistic analyses reveals upregulation of muscle regeneration (e.g., Myoz1 , Smyd1 ) and neurogenesis/neuromuscular junction stabilization (NMJ) stabilization genes (e.g., Dok7 , Musk ), highlighting a coordinated multi-lineage regenerative process. This work establishes an integrated regeneration-plus-support injectable strategy, offering a regenerative medicine-based approach that surpasses conventional bulking or sling therapies for SUI.
研究领域:
泌尿生殖医学
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再生医学
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组织工程
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干细胞生物学
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神经肌肉生物学
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生物材料
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转化医学
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产品关联
DOI
PubMed
高影响因子
Molecular Therapy-Nucleic Acids
·
2023
·
IF 8.8
Xinyi Gu,Shen Wang,Dongdong Li,Bo Jin,Zhidan Qi,Jin Deng,Chen Huang,Xiaofeng Yin
Peripheral nerve injury can lead to progressive muscle atrophy and poor motor function recovery, which is a difficult point of treatment, and the mechanism needs to be further explored. In previous studies we found that miR-142a-3p was significantly upregulated and persistently high expressed in denervated mouse skeletal muscle. Here, we show that overexpression of miR-142a-3p inhibited the growth and differentiation of C2C12 myoblast, while knockdown of miR-142a-3p had a promoting effect. In vitro, knockdown of miR-142a-3p in denervated mouse skeletal muscle effectively increased proliferating muscle satellite cells and ameliorated muscle atrophy. Mechanistically, the myoregulator Mef2a was proved to be an important downstream target of miR-142a-3p, and miR-142a-3p regulates skeletal muscle differentiation and regeneration by inhibiting the expression of Mef2a. The co-knockdown of Mef2a and miR-142a-3p effectively alleviated or offset the biological effects of miR-142a-3p knockdown. In conclusion, our data revealed that miR-142a-3p regulates neurogenic skeletal muscle atrophy by targeting Mef2a.
研究领域:
神经科学
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分子生物学
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肌肉骨骼疾病
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2021
·Vol. 16
·期 3
·035033
·
IF 3.715
Chengyuan Wang,Hui Wang,Qianping Guo,Xiaojie Ang,Bin Li,Fengxuan Han,Yingxi Fu,Weiguo Chen
In bladder tissue engineering, regeneration of muscle is of equal importance to epithelial regeneration. However, as yet there is no effective strategy for promoting bladder muscle regeneration. In this study we aim to promote bladder muscle regeneration by sustainably delivering heparin from a bilayer scaffold carrying stem cells. The bilayer scaffold [heparin–polycaprolactone (PCL)/bladder decellularized matrix (BAM) Hep-PB/PCL] comprises an electrospun layer (Hep-PB electrospun membrane) and a three-dimensional (3D) printed layer (PCL scaffold), fabricated via coaxial-electrospinning and 3D printing, respectively. Heparin was encapsulated into the core of the Hep-PB fibers with a core–shell structure to sustain its release. The morphology of the bilayer scaffold and the microstructure of the electrospun fibers were characterized. The release behavior of heparin from various electrospun membranes was evaluated. The role of Hep-PB in promoting myogenic differentiation of the adipose-derived stem cells (ADSCs) through sustainable release of heparin was also evaluated. After 7 d culture, Hep-PB/PCL scaffolds carrying ADSCs (defined as ASHP) were used for bladder reconstruction in a rat partial cystotomy model. The result shows that the PCL printed scaffold has ordered macropores (∼370 μm), unlike the compact microstructure of electrospun films. The Hep-PB membrane exhibits a sustained release behavior for heparin. This membrane also shows better growth and proliferation of ADSCs than the other membranes. The polymerase chain reaction results show that the expression of smooth muscle cell markers in ADSCs is enhanced by the Hep-PB scaffold. The results of retrograde urethrography and histological staining indicate that the bladder volume in the ASHP group recovers better, and the regenerated bladder muscle bundles are arranged in a more orderly fashion compared with the direct suture and bladder decellularized matrix groups. Therefore, findings from this study show that bladder muscle regeneration could be enhanced by bilayer scaffolds delivering heparin and carrying stem cells, which may provide a new strategy for bladder tissue engineering.
研究领域:
组织工程
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再生医学
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生物医学工程
·
干细胞生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Rong Huang,Chuang Cai,Wei-Wei Cheng,Yin-Jia Cheng,Wen-Long Liu,Yi-Han Ma,Ai-Qing Zhang,Si-Yong Qin
A highly hierarchical microstructure with aligned myofibers is a hallmark of native skeletal muscle. To treat volumetric muscle loss (VML), the development of tissue scaffolds that replicate the hierarchically aligned microstructures of the native muscle environment is both promising and challenging. Moreover, effective scaffolds should possess tunable components that enable specific functional modulations. This study proposes an injectable, self-assembling peptide liquid crystal (LC) hydrogel with hierarchical fiber alignment to support skeletal muscle regeneration. To emulate the physicochemical functions of skeletal muscle, Ti 3 C 2 T x MXene is incorporated as an exogenous component to enhance the mechanical strength, anti-inflammatory activity, and electrical conductivity of the LC hydrogel. The resulting Ti 3 C 2 T x /LC peptide hydrogel effectively guides myoblast alignment and promotes myogenic differentiation and angiogenesis. Compared to its unaligned non-liquid crystal (NLC) hydrogel counterpart, the aligned Ti 3 C 2 T x /LC hydrogel with a hierarchical microstructure significantly enhances new muscle tissue formation and functional recovery in a Sprague–Dawley (SD) rat model of VML. This study offers a robust and practical strategy for fabricating aligned hydrogel scaffolds with substantial potential in muscle tissue engineering and regenerative medicine.
研究领域:
生物材料
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组织工程
·
再生医学
·
生物医学工程
·
纳米技术
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材料科学
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Chem
·
2025
·
IF 19.6
Zhiwen Luo,Renwen Wan,Jiajun Qiu,Chen Chen,Yisheng Chen,Zhijie Zhao,Jie Mei,Yanwei He,Xinting Feng,Zhen Peng,Siwei Yin,Mowen Xu,Zhiheng Lin,James Hoipo Hui,Xuanyong Liu,Junming Sun,Shiyi Chen,Yaying Sun
Skeletal muscle inherently possesses regenerative capabilities, but recovery from severe volumetric muscle loss (VML) is often constrained, potentially resulting in loss of muscular functionality. Effective biomaterial interventions are rare. To address these gaps, we developed a novel injectable hydrogel, SiCP@InjGel, which utilizes in situ self-assembly to combine puerarin, chitosan, and mesoporous silica nanoparticles, targeting skeletal muscle repair. This hydrogel was rigorously tested in mice, rat, and porcine VML models through in vitro and in vivo experiments, demonstrating its ability to modulate the immune microenvironment, enhance myogenesis, and improve functional muscle recovery. Utilizing multiple state-of-the-art omics technologies, including mass cytometry and single-cell RNA sequencing, we identified that it increased Pdpn+ macrophages and MyoG+ muscle stem cells, reshaping the immune landscape and accelerating muscle regeneration at molecular and cellular resolutions. These findings establish SiCP@InjGel as a multifunctional biomaterial platform with significant translational potential for clinical management of severe skeletal muscle injuries.
研究领域:
再生医学
·
生物材料科学
·
免疫学
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分子生物学
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组织工程
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系统生物学
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转化医学
✓ 已验证
DOI
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 23
·7895-7910
·
IF 6.843
Guangxiu Cao,Wei He,Yubo Fan,Xiaoming Li
The repair of abdominal wall defects is currently a clinical challenge. A naturally derived extracellular matrix (ECM) such as small intestine submucosa (SIS) has received great attention in abdominal wall defect repair because of its remarkable bioactivity, biodegradability and tissue regeneration. The match between material degradation and tissue remodeling is very important for the realization of ideal repair effectiveness. In this study, a near-infrared (NIR) fluorescent dye Cy5.5 NHS ester was used to label ECM-based (ECMB) composites consisting of SIS and chitosan/elastin electrospun nanofibers for monitoring material degradation. The tissue remodeling in the ECMB composites for a full-thickness abdominal wall defect repair was systematically investigated by a series of tests including wall thickness measurement, muscle regeneration analysis and angiogenesis assessment. The main findings were: (1) real-time and noninvasive degradation monitoring of the ECMB composites until complete degradation could be realized by chemical conjugation with a Cy5.5 NHS ester. (2) In a full-thickness abdominal wall defect model, the explant thickness could be used as an intuitional indicator for evaluating the tissue remodeling efficiency in the ECMB composites, and the accuracy of this indicator was verified by various examinations including collagen deposition, angiogenesis, and muscle regeneration. The present study could provide new insight into evaluating tissue repair effectiveness of the ECMB composites.
研究领域:
生物医学工程
·
组织工程
·
再生医学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Wei Yu,Xiangqi Zhang,Muge Gu,Jiayu Wang,Yihui Zhang,Wenkai Zhang,Wei-En Yuan
Volumetric muscle loss (VML) is a severe form of muscle trauma that exceeds the regenerative capacity of skeletal muscle tissue, leading to substantial functional impairment. The abnormal immune response and excessive reactive oxygen species (ROS) accumulation hinder muscle regeneration following VML. Here, an interfacial cross-linked hydrogel-poly(ε-caprolactone) nanofiber composite, that incorporates both biophysical and biochemical cues to modulate the immune and ROS microenvironment for enhanced VML repair, is engineered. The interfacial cross-linking is achieved through a Michael addition between catechol and thiol groups. The resultant composite exhibits enhanced mechanical strength without sacrificing porosity. Moreover, it mitigates oxidative stress and promotes macrophage polarization toward a pro-regenerative phenotype, both in vitro and in a mouse VML model. 4 weeks post-implantation, mice implanted with the composite show improved grip strength and walking performance, along with increased muscle fiber diameter, enhanced angiogenesis, and more nerve innervation compared to control mice. Collectively, these results suggest that the interfacial cross-linked nanofiber-hydrogel composite could serve as a cell-free and drug-free strategy for augmenting muscle regeneration by modulating the oxidative stress and immune microenvironment at the VML site.
研究领域:
生物医学工程
·
组织工程
·
再生医学
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DOI
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Ying Wang,Ranjith Kumar Kankala,Yuan-Yuan Cai,Han-Xiao Tang,Kai Zhu,Jian-Ting Zhang,Da-Yun Yang,Shi-Bin Wang,Yu Shrike Zhang,Ai-Zheng Chen
Various conventional treatment strategies for volumetric muscle loss (VML) are often hampered by the extreme donor site morbidity, the limited availability of quality muscle flaps, and complicated, as well as invasive surgical procedures. The conventional biomaterial-based scaffolding systems carrying myoblasts have been extensively investigated towards improving the regeneration of the injured muscle tissues, as well as their injectable forms. However, the applicability of such designed systems has been restricted due to the lack of available vascular networks. Considering these facts, here we present the development of a unique set of two minimally invasively injectable modular microtissues, consisting of mouse myoblast (C2C12)-laden poly(lactic- co -glycolic acid) porous microspheres (PLGA PMs), or the micro-muscles, and human umbilical vein endothelial cell (HUVEC)-laden poly(ethylene glycol) hollow microrods (PEG HMs), or the microvessels. Besides systematic in vitro investigations, the myogenic performance of these modular composite microtissues, when co-injected, was explored in vivo using a mouse VML model, which confirmed improved in situ muscle regeneration and remolding. Together, we believe that the construction of these injectable modular microtissues and their combination for minimally invasive therapy provides a promising method for in situ tissue healing.
研究领域:
组织工程
·
再生医学
·
生物医学工程
·
细胞生物学
·
肌肉骨骼研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Xiangyu Dong,Shan Su,Qian Sun,Peng Wang,Qian Hu,Qiang Wei
The extracellular matrix (ECM) plays a crucial role in regulating cellular behaviors and functions. However, the impact of ECM topography on muscle cell adhesion and differentiation remains poorly understood from a mechanosensing perspective. In this study, we fabricated aligned and random electrospun polycaprolactone (PCL) nanofibers to mimic the structural characteristics of ECM. Mechanism investigations revealed that the orientation of nanofibers promoted C2C12 polarization and myogenesis through Rac-related signaling pathways. Conversely, cells cultured on random fibers exhibited spreading behavior mediated by RhoA/ROCK pathways, resulting in enhanced stress fiber formation but reduced capacity for myogenic differentiation. Our findings highlight the critical role of an ECM structure in muscle regeneration and damage repair, providing novel insights into mechanosensing mechanisms underlying muscle injury diseases.
研究领域:
生物医学工程
·
细胞生物学
·
组织工程
·
再生医学
✓ 已验证
DOI
高影响因子
EXPERIMENTAL PHYSIOLOGY
·
2021
·Vol. 106
·期 4
·958-971
·
IF 2.969
Xia Yan,Xuli Gao,Qiaohua Niu,Xin Peng,Jie Zhang,Xiufeng Ma,Yanhong Wei,Huiping Wang,Yunfang Gao,Hui Chang
New Findings What is the central question of this study? The aim was to investigate whether diaphragm hypertrophy and gastrocnemius atrophy during hibernation of Daurian ground squirrels involve differential regulation of protein metabolism and regeneration. What is the main finding and its importance? We clarified the differences in protein metabolism and muscle regenerative potential in the diaphragm and gastrocnemius of hibernating ground squirrels, reflecting the different adaptability of muscles. Are differences in the regulation of protein metabolism and regeneration involved in the different phenotypic adaptation mechanisms of muscle hypertrophy and atrophy in hibernators? Two fast-type muscles (diaphragm and gastrocnemius) in summer active and hibernating Daurian ground squirrels were selected to detect changes in cross-sectional area (CSA) and protein expression indicative of protein synthesis metabolism (protein expression of P-Akt, P-mTORC1, P-S6K1 and P-4E-BP1), protein degradation metabolism (MuRF1, atrogin-1, calpain-1, calpain-2, calpastatin, desmin, troponin T, Beclin1 and LC3-II) and muscle regeneration (MyoD, myogenin and myostatin). In the hibernation group compared with the summer active group, the CSA of the diaphragm muscle increased significantly by 26.1%, whereas the CSA of the gastrocnemius muscle decreased significantly by 20.4%. Our study also indicated that increased protein synthesis, decreased protein degradation and increased muscle regenerative potential contributed to diaphragm muscle hypertrophy, whereas decreased protein synthesis, increased protein degradation and decreased muscle regenerative potential contributed to gastrocnemius muscle atrophy. In conclusion, the differences in muscle regeneration and regulatory pattern of protein metabolism might contribute to the different adaptive changes observed in the diaphragm and gastrocnemius muscles of ground squirrels.
研究领域:
生理学
·
生物化学
·
分子生物学
·
动物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）