Engineering an Injectable Scaffold with Enhanced ECM Mimicry for Cell Delivery and Tissue Regeneration

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Biomimetic scaffolds mimicking the extracellular matrix (ECM) are crucial for cell-based therapies and tissue regeneration.
• Existing scaffolds often have limitations in structural uniformity, injectability, and in situ gelation.

Purpose of the Study:

• To formulate and characterize CHyCoGel, a novel injectable ECM-mimetic hydrogel scaffold.
• To evaluate the cytocompatibility and in vivo efficacy of CHyCoGel for tissue regeneration, particularly in wound healing.

Main Methods:

• CHyCoGel was formulated using chitosan, hyaluronic acid, chondroitin sulfate, and an amphiphilic stabilizer.
• Primary dermal fibroblasts (PDFs) were encapsulated within CHyCoGel.
• Cell viability, cytoskeletal structure, and gene expression (α-SMA, fibronectin, Col1A1, TGF-β) were assessed.
• In vivo wound healing studies were conducted, evaluating epithelialization, skin appendage regeneration, angiogenesis (VEGF), and ECM remodeling (collagen type I).

Main Results:

• CHyCoGel demonstrated improved structural uniformity and in situ gelation for cell encapsulation and minimally invasive delivery.
• Encapsulated PDFs exhibited high viability, organized cytoskeletal structures, and modulated tissue remodeling genes.
• In vivo, PDF-loaded CHyCoGel significantly enhanced wound healing, epithelialization, and skin appendage regeneration.
• CHyCoGel promoted angiogenesis via VEGF upregulation and balanced ECM remodeling with enhanced type I collagen expression.

Conclusions:

• CHyCoGel is a cytocompatible and bioactive scaffold with potential for cell-based therapies.
• The scaffold effectively directs cellular behavior and promotes integrated tissue regeneration.
• CHyCoGel shows promise for treating chronic and complex wounds.