Modulating design parameters to drive cell invasion into hydrogels for osteochondral tissue formation

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Orthopedics

Background:

• Acellular hydrogels are promising for osteochondral defect repair, requiring cell infiltration and extracellular matrix deposition.
• Understanding how hydrogel physicochemical properties influence cell behavior is crucial for effective tissue regeneration.
• Current knowledge gaps exist regarding specific hydrogel properties that enhance cell migration and tissue formation.

Purpose of the Study:

• To investigate the impact of various hydrogel physicochemical properties on cell migration and subsequent tissue formation.
• To evaluate hydrogel performance using in vitro, ex vivo, and in vivo models for osteochondral defect repair.

Main Methods:

• Three hydrogel platforms were synthesized: GelMA (varying degree of functionalization - DoF), norbornene hyaluronic acid (norHA) (varying degradability), and tyramine hyaluronic acid (THA) (with collagen fibrils).
• Human mesenchymal stromal cell (hMSC) migration was assessed in vitro using a 3D spheroid assay.
• Chondrocyte migration was studied ex vivo in a bovine cartilage ring model, and tissue repair was evaluated in vivo in a mouse osteochondral defect model.

Main Results:

• Lower GelMA DoF enhanced ex vivo migration; collagen addition to THA improved both in vitro and ex vivo migration.
• MMP-degradable norHA did not improve in vitro or ex vivo cell infiltration but significantly increased in vivo tissue formation.
• Hydrogels promoting greater cell migration in vitro/ex vivo generally showed increased in vivo tissue formation, with norHA being an exception.

Conclusions:

• Hydrogel modifications (DoF, degradable crosslinkers, collagen) can effectively control cell migration and tissue formation for osteochondral repair.
• The study highlights the critical importance of employing multiple models (in vitro, ex vivo, in vivo) for comprehensive biomaterial assessment.
• Results underscore that model choice can influence outcomes, necessitating diverse testing for successful clinical translation of hydrogel therapies.