Progress in applications of anti-senescence materials for tissue repair

doi:10.3969/j.issn.1674-8115.2025.11.012

Abstract

Abstract:

Tissue repair is an important physiological process after tissue injury, but it is often disrupted by tissue fibrosis, oxidative stress, and other problems, accompanied by cellular senescence. Cellular senescence refers to the proliferation stagnation and function decline of cells under adverse stimuli, which plays a bidirectional regulatory role in tissue repair. In the early stage of wound healing, it can limit fibrosis and induce cell plasticity, thus promoting repair. Nevertheless, the long-term accumulation of senescent cells will interfere with the normal proliferation and differentiation of cells and hinder the repair process. In recent years, with the development of histology and cell biology, the mechanisms of tissue repair and cellular senescence have been deeply studied, providing a theoretical basis for the application of anti-senescence materials to tissue repair. Ingredients in anti-senescence materials, such as anti-senescence drugs, energy supplements, and antioxidants, play a favorable role by inducing apoptosis, activating autophagy, reversing the senescence process, and other mechanisms. The application of these anti-senescence materials provides new ideas to solve clinical problems like tissue fibrosis in chronic wounds, and is expected to become an effective means to intervene in tissue regeneration. In recent years, anti-senescence materials have been widely used in tissue regeneration and repair. This review may promote the translation and application of more fundamental research and provide references for clinical tissue repair.

Key words: cellular senescence, tissue repair, anti-senescence materials, tissue regeneration engineering

CLC Number:

R641

HOU Senlin, DENG Xiangtian, ZHENG Tingjia, HAN Yifei, LIU Shen. Progress in applications of anti-senescence materials for tissue repair[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(11): 1527-1535.

Figures/Tables 4

TrendMD

References 58

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Feature	Acute wound	Chronic wound
SASP secretory pattern	Short-term, mainly promoting repair	Long-term, mainly promoting inflammation
SASP secretory substances	Growth factors such as TGF-β, ECM remodeling enzymes such as MMPs, anti-inflammatory cytokines such as IL-10, etc	Proinflammatory factors such as IL-1β and TNF-α, and growth inhibitors such as sFRP
Oxidative stress level	Controllable, with a transient rise in ROS	Persistent high-level, causing accumulation of DNA damage
Microenvironment remediation ability	Dynamic balance (orderly ECM remodeling)	Imbalance (excessive ECM degradation or fibrosis)

Feature	Acute wound	Chronic wound
SASP secretory pattern	Short-term, mainly promoting repair	Long-term, mainly promoting inflammation
SASP secretory substances	Growth factors such as TGF-β, ECM remodeling enzymes such as MMPs, anti-inflammatory cytokines such as IL-10, etc	Proinflammatory factors such as IL-1β and TNF-α, and growth inhibitors such as sFRP
Oxidative stress level	Controllable, with a transient rise in ROS	Persistent high-level, causing accumulation of DNA damage
Microenvironment remediation ability	Dynamic balance (orderly ECM remodeling)	Imbalance (excessive ECM degradation or fibrosis)

Anti-senescence material	Injury type	Mechanism of action	Biocompatibility	Experimental stage and evaluation	Reference
Dasatinib + quercetin environment-responsive hydrogel	Myocardial injury	Senolytic	High biocompatibility, low toxicity, and no obvious side effects	Clinical randomized controlled trial	[35]
Metformin + zinc ion hydrogel	Traumatic skin defects, burns	Activating autophagy	High biocompatibility, low toxicity, and easy metabolism	Mouse experiment	[36]
Resveratrol + angiopoietin 2 hydrogel	Bone tissue injury	Activating autophagy	High biocompatibility, low toxicity, and no obvious side effects	Rat experiment	[37]
Yap1 protein exosome hydrogel	Tendon injury	Inhibiting SASP	High biocompatibility, low toxicity, and no obvious side effects	Rat experiment	[38]
Microneedle patches loaded with taurine	Soft tissue injury	Inhibiting SASP	High biocompatibility, low toxicity, and no obvious side effects	Rat experiment	[39]
Dynamic self-healing hydrogel loaded with melatonin	Intervertebral disc annulus fibrosus injury	Enhancing energy supply	High biocompatibility, low toxicity, and no obvious side effects	Rat experiment	[40]
Hydrogel loaded with myelinated mesenchymal stem cells	Bone tissue injury	Enhancing energy supply	High biocompatibility, low toxicity, and no obvious side effects	Mouse experiment	[41]
Nano-thylakoid membrane system	Cartilage injury	Enhancing energy supply	High biocompatibility, low toxicity, and no obvious side effects	Animal experiment (without specifying species)	[42]
PLGA-PEG nanodelivery system loaded with ginsentriol	Osteoarthritis	Reversing senescent cells	Lower side effects than systemic administration, reduced risk of infection from intra-articular injection	Mouse and human tissue in vitro experiment	[43]
Pha-encapsulated CaSi₂ nanoparticles releasing H₂	Bone defect	Inhibiting oxygenated stress	High biocompatibility, low toxicity, and easy metabolism	Mouse experiment	[44]
Hydrogel loaded with synovial mesenchymal stem cells	Cartilage injury	Reversing senescent cells	High biocompatibility, low toxicity, and easy metabolism	Rat experiment	[45]
Biological heterojunctions releasing gaseous H₂Se	Stalled healing of infectious wounds	Inhibiting oxygenated stress	High biocompatibility, low toxicity, and easy metabolism	Rat experiment	[46]
PEG liposomes targeting CD9	Skin injury	Reversing senescent cells	High targeting, efficient drug utilization, and low toxicity	Cell in vitro experiment	[47]
Honokiol	Silicosis	Inhibiting oxygenated stress	High biocompatibility, low toxicity, and easy metabolism	Mouse experiment	[48]

Anti-senescence material	Injury type	Mechanism of action	Biocompatibility	Experimental stage and evaluation	Reference
Dasatinib + quercetin environment-responsive hydrogel	Myocardial injury	Senolytic	High biocompatibility, low toxicity, and no obvious side effects	Clinical randomized controlled trial	[35]
Metformin + zinc ion hydrogel	Traumatic skin defects, burns	Activating autophagy	High biocompatibility, low toxicity, and easy metabolism	Mouse experiment	[36]
Resveratrol + angiopoietin 2 hydrogel	Bone tissue injury	Activating autophagy	High biocompatibility, low toxicity, and no obvious side effects	Rat experiment	[37]
Yap1 protein exosome hydrogel	Tendon injury	Inhibiting SASP	High biocompatibility, low toxicity, and no obvious side effects	Rat experiment	[38]
Microneedle patches loaded with taurine	Soft tissue injury	Inhibiting SASP	High biocompatibility, low toxicity, and no obvious side effects	Rat experiment	[39]
Dynamic self-healing hydrogel loaded with melatonin	Intervertebral disc annulus fibrosus injury	Enhancing energy supply	High biocompatibility, low toxicity, and no obvious side effects	Rat experiment	[40]
Hydrogel loaded with myelinated mesenchymal stem cells	Bone tissue injury	Enhancing energy supply	High biocompatibility, low toxicity, and no obvious side effects	Mouse experiment	[41]
Nano-thylakoid membrane system	Cartilage injury	Enhancing energy supply	High biocompatibility, low toxicity, and no obvious side effects	Animal experiment (without specifying species)	[42]
PLGA-PEG nanodelivery system loaded with ginsentriol	Osteoarthritis	Reversing senescent cells	Lower side effects than systemic administration, reduced risk of infection from intra-articular injection	Mouse and human tissue in vitro experiment	[43]
Pha-encapsulated CaSi₂ nanoparticles releasing H₂	Bone defect	Inhibiting oxygenated stress	High biocompatibility, low toxicity, and easy metabolism	Mouse experiment	[44]
Hydrogel loaded with synovial mesenchymal stem cells	Cartilage injury	Reversing senescent cells	High biocompatibility, low toxicity, and easy metabolism	Rat experiment	[45]
Biological heterojunctions releasing gaseous H₂Se	Stalled healing of infectious wounds	Inhibiting oxygenated stress	High biocompatibility, low toxicity, and easy metabolism	Rat experiment	[46]
PEG liposomes targeting CD9	Skin injury	Reversing senescent cells	High targeting, efficient drug utilization, and low toxicity	Cell in vitro experiment	[47]
Honokiol	Silicosis	Inhibiting oxygenated stress	High biocompatibility, low toxicity, and easy metabolism	Mouse experiment	[48]