An injectable GelMA hydrogel improves Achilles tendon repair through local microenvironment modulation

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Surgery

Background:

• Achilles tendon injuries present significant clinical challenges due to poor healing and disorganized matrix remodeling.
• Current treatments often fall short in fully restoring tendon function.
• Developing novel strategies for enhanced tendon repair is crucial.

Purpose of the Study:

• To develop and evaluate an injectable gelatin methacryloyl (GelMA) hydrogel system for sustained local delivery of GsMTx4, a mechanosensitive ion channel modulator.
• To assess the therapeutic potential of this GelMA-GsMTx4 hydrogel for promoting Achilles tendon healing in vitro and in vivo.
• To investigate the effects of the hydrogel on cellular behavior, matrix remodeling, and mechanosensitive responses in injured tendons.

Main Methods:

• Fabrication of an injectable GelMA hydrogel loaded with GsMTx4.
• Characterization of the hydrogel's physicochemical properties, injectability, and local retention.
• In vitro evaluation of cell compatibility, matrix degradation, and tendon-related marker expression.
• In vivo assessment of Achilles tendon healing in an injury model, including histological analysis and collagen organization evaluation.
• Analysis of extracellular matrix remodeling and mechanosensitive pathway modulation.

Main Results:

• The developed GelMA hydrogel demonstrated favorable properties, including injectability and good local retention.
• In vitro studies showed improved cell compatibility, reduced matrix degradation, and enhanced expression of tendon-specific markers with the hydrogel treatment.
• In vivo administration of the GelMA-GsMTx4 hydrogel promoted histological repair in the Achilles tendon injury model.
• The treatment led to improved collagen organization and alleviated pathological changes in the injured tissue.
• Beneficial effects were associated with modulated extracellular matrix remodeling and mechanosensitive responses.

Conclusions:

• Injectable GelMA hydrogels loaded with GsMTx4 provide a promising platform for sustained local drug delivery.
• This therapeutic strategy effectively enhances Achilles tendon healing by improving tissue repair, collagen organization, and matrix remodeling.
• The GelMA-GsMTx4 hydrogel represents a potential novel local therapeutic approach for managing Achilles tendon injuries.