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Collagen-Enriched Immunomodulatory Hydrogel for Tendon Regeneration.
Shivam Patel1, Jeremy Pan1, An Phong Nguyen1
1Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Gels (Basel, Switzerland)
|April 27, 2026
Summary
This study developed new hydrogels for rotator cuff tendon injury (RCTI) that reduce inflammation and support regeneration. These materials effectively deliver anti-inflammatory peptides and show promise for tendon tissue engineering.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Immunology
Background:
- Rotator cuff tendon injury (RCTI) is worsened by inflammation mediated by TLR4 and TREM1 signaling pathways.
- Effective tendon tissue engineering requires strategies to manage inflammation and promote regeneration.
Purpose of the Study:
- To engineer and assess the immunocompatibility of a tendon-mimetic hydrogel (chitosan-polyvinyl alcohol blend with Collagen-I).
- To evaluate the delivery of LR12 peptide for managing TREM1-driven inflammation in RCTI.
Main Methods:
- Synthesis of chitosan-PVA-HEMA-Acrylic acid (CPHA) and CPHA-Collagen-I (CPHA-C) hydrogels.
- Characterization of hydrogel properties (porosity, amphiphilicity) and LR12 release kinetics.
- Assessment of immunomodulatory effects in LPS-challenged RAW264.7 macrophages and tenocytes.
Main Results:
- CPHA and CPHA-C hydrogels demonstrated good porosity and amphiphilicity.
- Progressive LR12 release for 7 days, with enhanced TREM1 inhibition in macrophages.
- Hydrogels showed immunocompatibility, reduced oxidative stress, and modulated TGFβ/TLR4 ratios.
Conclusions:
- CPHA and CPHA-C hydrogels are promising biomaterials for tendon tissue engineering.
- These hydrogels can deliver anti-inflammatory agents and manage inflammatory responses in RCTI.
- The developed hydrogels support regenerative processes for tendon repair.

