TGF-β1 presenting enzymatically cross-linked injectable hydrogels for improved chondrogenesis

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Cartilage defects pose significant clinical challenges, often requiring advanced tissue engineering solutions.
• Current strategies struggle with sustained delivery of crucial growth factors like TGF-β1.
• Injectable hydrogels offer minimally invasive delivery for cell and growth factor encapsulation.

Purpose of the Study:

• To develop and characterize a novel injectable hydrogel for cartilage tissue engineering.
• To evaluate the hydrogel's capacity for sustained release and bioactivity of TGF-β1.
• To assess the hydrogel's efficacy in promoting chondrogenesis of encapsulated cells.

Main Methods:

• Fabrication of carboxymethyl cellulose (CMC), sulfated carboxymethyl cellulose (sCMC), and gelatin hydrogels cross-linked with H2O2.
• Encapsulation of infrapatellar fat pad derived MSCs (IFP MSCs) and articular chondrocytes (ACs) with TGF-β1.
• In vitro assessment of hydrogel mechanical properties, TGF-β1 sequestration, bioactivity, cell viability, and cartilage matrix deposition.

Main Results:

• The 2mM H2O2 cross-linked hydrogel exhibited superior mechanical properties and in vitro cartilage formation.
• Hydrogels effectively sequestered >90% of TGF-β1 for over 4 weeks, maintaining its bioactivity.
• TGF-β1 loaded hydrogels significantly enhanced hyaline cartilage marker expression and deposition while reducing fibrocartilage and hypertrophy markers.

Conclusions:

• TGF-β1 immobilized CMC/sCMC/gelatin injectable hydrogels provide a promising strategy for cartilage tissue engineering.
• The system enables sustained presentation of bioactive TGF-β1, promoting chondrogenesis and hyaline cartilage formation.
• This approach offers a cost-effective and translatable solution for cartilage defect repair.