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Recombinant humanized collagen ameliorates ischemic myopathy through limiting natural IgM-mediated lectin complement
Danyang Huang1, Zihan Ma2, Jing Wang2
1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China; College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China; Department of Plastic Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
Recombinant humanized collagens (rhCol I and III) promote muscle regeneration in peripheral artery disease (PAD) by reducing complement activation. These collagens offer a promising biomaterial therapy for ischemic myopathy.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Vascular Biology
Background:
- Advanced lower extremity peripheral artery disease (PAD) lacks effective therapeutics for repairing ischemic muscles.
- Current treatments struggle to create supportive microenvironments for muscle regeneration.
Purpose of the Study:
- To investigate the efficacy of recombinant humanized collagen type I and III (rhCol I and rhCol III) in regenerating skeletal muscle after ischemic injury.
- To elucidate the underlying mechanism of collagen's protective effects in ischemic myopathy.
Main Methods:
- Inducing hindlimb ischemia in a preclinical model.
- Administering repeated intramuscular injections of rhCol I or rhCol III.
- Assessing muscle regeneration, myofiber structure, and proteomic signatures.
- Investigating the interaction between rhCol and natural IgM (nIgM) in complement activation.
Main Results:
- rhCol I and rhCol III injections preserved myofiber structure and accelerated regeneration within one week.
- Proteomic analysis revealed reduced lectin complement activation in treated muscles.
- A competitive binding between rhCol and nIgM was identified, inhibiting complement activation.
- Long-term treatment demonstrated sustained protection, improved muscle pathology, and enhanced function.
Conclusions:
- rhCol I and rhCol III create a protective microenvironment by inhibiting complement activation.
- These collagens represent a promising biomaterial-based therapeutic approach for ischemic myopathy in PAD.
- The findings support the use of rhCol for treating muscle damage associated with PAD.

