Zn‐DHM Nanozymes Enhance Muscle Regeneration Through ROS Scavenging and Macrophage Polarization in Volumetric Muscle Loss Revealed by Single‐Cell Profiling

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Abstract Volumetric muscle loss (VML) is a severe condition in which the of skeletal surpasses body's intrinsic repair capabilities, leading to irreversible functional deficits and potential disability, with persistent inflammation impaired myogenic differentiation. To address these challenges, novel zinc‐dihydromyricetin (Zn‐DHM) nanozyme superoxide dismutase (SOD)‐like activity developed, designed neutralize excessive reactive oxygen species (ROS) restore oxidative balance. Zn‐DHM mitigates stress promotes polarization macrophages from proinflammatory M1 phenotype anti‐inflammatory M2 phenotype, thereby reducing chronic creating conducive environment for repair. Further, significantly enhances differentiation C 2 12 cells, accelerating wound healing processes. These studies confirm biosafety low toxicity Zn‐DHM. As per murine tibialis anterior VML model, effectively suppresses markedly improves outcomes. Single‐cell RNA sequencing reveals that treatment increases expression macrophage markers proliferation capacity stem cells (MuSCs). In addition, intercellular communication analysis interactions between MuSCs group, suggesting may drive tissue regeneration through activation GAS Notch signaling pathways.

Language: Английский

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Biomimetic fabrication bioprinting strategies based on decellularized extracellular matrix for musculoskeletal tissue regeneration: Current status and future perspectives

Materials & Design, Journal Year: 2024, Volume and Issue: 243, P. 113072 - 113072

Published: June 6, 2024

Musculoskeletal disorders, as one of the prevalent categories ailments, exert significant impacts on individuals' lives, occupations, and physical activities. Degenerative changes, injuries, infections, tumor resections causing defects in musculoskeletal tissues such cartilage, bones, skeletal muscles, menisci, ligaments, rotator cuffs can detrimentally affect patients' quality life mental well-being. Traditional autologous allogeneic transplantations have been clinically employed. However, transplantation suffers from limitation a finite number transplantable tissues, while faces challenges immune rejection. The extracellular matrix (ECM) serves natural scaffold for cells to fulfill physiological functions adhesion, proliferation, differentiation. Decellularized (dECM) emerges promising biomaterial generated through specific tissue or organ decellularization. Leveraging 3D bioprinting technology, dECM-based biomaterials enable customized printing construction. This study reviews various decellularization techniques, post-decellularization strategies, commonly used technologies. It summarizes integration with technology applied system research. These investigations showcase exciting potential system, offering prospects clinical translation orthopedics.

Language: Английский

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Bioengineered Constructs as a Tissue Engineering-Based Therapy for Volumetric Muscle Loss

Tissue Engineering Part B Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Severe skeletal muscle injuries involving substantial tissue loss can significantly impair strength and functionality, reducing the quality of life for affected individuals. Such injuries, termed volumetric loss, require extensive clinical intervention, as body's innate healing mechanisms are insufficient to regenerate functional muscle. The current standard care primarily involves autologous transfer, with some consideration acellular synthetic constructs. However, both approaches have limited therapeutic efficacy, presenting challenges such donor-site morbidity, infection risks, suboptimal recovery. Over past decade, engineering (SMTE) has emerged a promising strategy regenerating through bioengineered Advanced biofabrication techniques, including bioprinting, further enabled development constructs that closely mimic native architecture. Given these advancements, critical review recent strategies, their achievements, limitations is necessary. This examines spectrum developed from various biomaterials evaluates potential. Special emphasis placed on 3D bioprinting strategies role in creating physiologically relevant restoration. In addition, integration machine learning optimizing construct design, predicting cellular behavior, enhancing discussed. indicates despite significant progress SMTE, key remain, replicating complex structural organization tissue, minimizing fibrosis, achieving vascularization innervation functional, strengthened Future research should address barriers while prioritizing translational, clinically regenerative efforts focus advancing scalable, construct-based treatments readily available at point easily managed surgical settings.

Language: Английский

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Sequential simulation of regeneration-specific microenvironments using scaffolds loaded with nanoplatelet vesicles enhances bone regeneration

Bioactive Materials, Journal Year: 2025, Volume and Issue: 50, P. 475 - 493

Published: April 26, 2025

Language: Английский

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Engineering the immune and fibrotic response in VML

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

Abstract Volumetric muscle loss (VML) provides a significant challenge for regeneration, despite current treatments with free functional transfer. VML injury overwhelms the native process of wound healing, leading to dysregulated immune response and eventually fibrosis. Tissue engineered grafts are promising method treatment without donor site morbidity. not only provide structural support, but also address myogenic deficit by transplanting satellite cells myoblasts supplement those lost as result secrete additional stimuli create more pro‐regenerative microenvironment. However, adequate requires modulation limiting fibrotic deposition. To this, some approaches have targeted other involved in such macrophages, regulatory T cells, fibroadipogenic progenitor, myofibroblasts. Treatments that at same time co‐delivering either or modulatory signals demonstrated increased success. One limitation is many these being tested models exhibit limited fibrosis, observed benefits may be seen clinically relevant scenarios. Future studies incomplete understanding cellular signalling responses ameliorate We summation recent strategies employed this purpose, well predictions about new yet utilized VML. image

Language: Английский

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A sandwich-like nanofibrous scaffold with macrophage phenotype transformation and myogenic differentiation for skeletal muscle regeneration

Bioactive Materials, Journal Year: 2025, Volume and Issue: 51, P. 211 - 230

Published: May 13, 2025

Language: Английский

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Deriving skeletal muscle cells from adipose-derived stem cells: Current differentiation strategies

Chinese Medical Journal, Journal Year: 2024, Volume and Issue: 137(12), P. 1498 - 1500

Published: May 27, 2024

To the Editor: Adipose-derived stem cells (ASCs) are promising multipotent for regeneration of skeletal muscle (SM) tissues.[1] However, low myogenic differentiation ability limits application.[2] Therefore, it is necessary to summarize current strategy improve efficiency. Traditional methods (biochemical induction) and non-traditional strategies (co-culture, biomechanical approaches, biomaterial utilization) commonly used ASCs into lineages. Although both can effectively induce cells, cellular unhealthy or immature status still greatest challenge researcher. Theoretically, combination traditional has potential significantly enhance myogenesis with remarkable efficacy, however, evidence currrently insufficient. This review discusses strategies, as well several motheds above inducing [Figure 1].Figure 1: Overview on ASCs. Figure created BioRender.com. ASCs: cells; ECM: Extracellular matrix; FGF: Fibroblast growth factor; HUVEC: Human umbilical vein endothelial cell; IL: Interleukin; VEGF: Vascular factor.Traditional myogenesis: present biochemical features that consistent when exposed various induction factors. The DNA methylation inhibitor 5-azacytidine multi-nucleated cells.[3] addition chemokine interleukin (IL) 6 culture media promotes towards cell lineage.[4] factors (FGFs), such FGF-8, lineage.[5] Additionally, H2 was shown MYOD1 gene expression ASCs.[6] Moreover, polyhydroxylated fullerenes, fullerenol C60, have demonstrated excellent enhancing effects transcription (TFs) in human ASCs.[7] Non-traditional dependent coupling precise regulation types SM cells. Several studies confirmed participate generation myotubes presence differentiating myoblasts (C2C12 cells). Milner et al[8] analyzed profiles muscle-specific genes (myogenin [MyoG] myosin heavy chain [MHC]) co-cultured C2C12 detected single, unfused expressing MHC, indicating fuse form myotubes. co-culture (HUVECs) myotube formation increase MHC mRNA ASCs.[9] Biophysical stimuli alone early-stage myogenesis-related genes.[10] In addition, mechanical signals reported promote more than stimulation alone. For example, subjected a dynamic cyclic uniaxial strain (10% at 1 Hz) produced MHC-positive enhanced MyoG compared conditions factor supplementation alone.[11] cooperative may be required Studies showed decorin, component extracellular matrix (ECM), inhibit activities myostatin vitro.[12] study focused biomaterials derived from decellularized (dECM) engineering tissues.[2] Abbas al[9] physical dECM, vascular (VEGF), HUVECs increased ASCs, combinations tissues. material stiffness play critical role regulating differentiation-related pathways precursor Similarly, also sense microenvironment differentiate functional substrates mimic ECM SM.[13] mounting biological indicates alignment greater terminal differentiation. Ergene al[14] found acrylamide substrate an aligned pattern, opposed unpatterned matrix, induced fusion markers promoted formation. equipped micro- nanoscale geometric parameters. Previous while microscale topographic cytoskeletal proteins formation, fibers efficient formed much longer.[15] Furthermore, coating conductive gold nanoparticles upregulated markers, which attributed changes inherent conductivity subsequent upregulation myogenesis.[16] chemical characteristics synthetic materials affect A few specific been maturation phenotype Among different suitable constructing cell-culture scaffolds, those biodegradable properties appear particularly attractive. tailored according topographic, porosity, other parameters control responses.[17] Myogenic differentiated important tissues field tissue engineering. micro-environment, respond stimulation, conditions, features. Hence, clarification crucial gaining appreciation processes modify Funding project supported by National Natural Science Funder China (No. 81873939), Peking University Medicine Sailing Program Young Scholars'Scientific & Technological Innovation (NO. BMU2024YFJHPY030), Postdoctoral Fellowship CPSF GZC20230151). We thank International Editing polishing this manuscript. Conflicts interest None.

Language: Английский

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Decellularized Extracellular Matrix Scaffolds: Recent Advances and Emerging Strategies in Bone Tissue Engineering

ACS Biomaterials Science & Engineering, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Bone tissue engineering (BTE) is a complex biological process involving the repair of bone with proper neuronal network and vasculature as well surrounding soft tissue. Synthetic biomaterials used for BTE should be biocompatible, support regeneration, eventually degraded in situ replaced newly generated Recently, various forms graft materials such hydrogel, nanofiber scaffolds, 3D printed composite scaffolds have been developed application. Decellularized extracellular matrix (DECM), kind natural material obtained from specific tissues organs, has certain advantages over synthetic exogenous biomaterial-derived grafts. Moreover, DECM can wide range sources possesses strong molding abilities, structures, bioactive factors. Although shown robust osteogenic, proangiogenic, immunomodulatory, defect healing potential, rapid degradation limited mechanical properties improved bench-to-bed translation BTE. This review summarizes recent advances DECM-based discusses emerging strategies

Language: Английский

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Autophagy in Muscle Regeneration: Mechanisms, Targets, and Therapeutic Perspective

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11901 - 11901

Published: Nov. 6, 2024

Autophagy maintains the stability of eukaryotic cells by degrading unwanted components and recycling nutrients plays a pivotal role in muscle regeneration regulating quiescence, activation, differentiation satellite cells. Effective is vital for maintaining health homeostasis. However, under certain disease conditions, such as aging, can fail due to dysfunctional Dysregulated autophagy may limit cell self-renewal, hinder differentiation, increase susceptibility apoptosis, thereby impeding regeneration. This review explores critical regeneration, emphasizing its interplay with apoptosis recent advances research related diseases characterized impaired Additionally, we discuss new approaches involving regulation promote macrophage polarization, enhancing We suggest that utilizing therapy biomaterials modulate could be promising strategy supporting hope this will provide insights into treatment

Language: Английский

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Challenges in Application: Gelation Strategies of DAT-Based Hydrogel Scaffolds

Tissue Engineering Part B Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: April 26, 2024

Decellularized Adipose Tissue (DAT) has great clinical applicability, owing to its abundant source material, natural extracellular matrix (ECM) microenvironment, and non-immunogenic attributes, rendering it a versatile resource in the realm of tissue engineering. However, practical implementations are confronted with multifarious limitations. Among these, selection an appropriate gelation strategy serves as foundation for adapting diverse contexts. The crosslinking strategies under varying physical or chemical conditions exert profound influences on ultimate morphology therapeutic efficacy DAT. This review sums up processes DAT decellularization subsequent gelation, specific emphasis employed recent experimental applications expounds upon methodologies, underlying principles, implications different strategies, aiming offer insights inspiration application engineering advance research scaffold development.

Language: Английский

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