Macroporous Granular Hydrogels Functionalized with Aligned Architecture and Small Extracellular Vesicles Stimulate...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Surgery

Background:

• Osteoporotic tendon-to-bone healing (TBH) after rotator cuff repair (RCR) presents significant challenges.
• Existing scaffolds lack aligned architecture, immunomodulatory capacity, and macroporous structures needed for effective TBH.

Purpose of the Study:

• To fabricate and evaluate a novel macroporous hydrogel scaffold (MHA-sEVs) with aligned architecture and immunomodulatory properties for osteoporotic TBH.
• To investigate the scaffold's ability to promote cell infiltration, tissue integration, and bone regeneration while modulating inflammation.

Main Methods:

• Fabrication of a macroporous hydrogel scaffold (MHA-sEVs) using sodium alginate, hyaluronic acid, and small extracellular vesicles (sEVs) from adipose-derived stem cells.
• In vivo evaluation in an osteoporotic RCR model to assess TBH, tissue integration, and biomechanical strength.
• In vitro studies on cell-hydrogel interactions, including tenogenic differentiation and macrophage polarization via the NF-κb pathway.

Main Results:

• MHA-sEVs significantly improved cell infiltration and tissue integration due to its macroporous structure.
• The scaffold promoted TBH by enhancing tendon repair and bone regeneration through its aligned architecture and anti-inflammatory effects.
• Biomechanical strength was approximately doubled compared to controls, suggesting reduced retear rates.
• Scaffold alignment induced tenogenic differentiation; sEVs improved M1 macrophage mitochondrial function and inhibited M1 polarization.

Conclusions:

• MHA-sEVs offer a promising strategy for promoting osteoporotic tendon-to-bone healing.
• The scaffold's aligned macroporous architecture and immunomodulatory properties are key to its efficacy.
• This approach holds potential for future clinical applications in RCR and other orthopedic repairs.