Injectable GelMA Cryogel Microspheres for Modularized Cell Delivery and Potential Vascularized Bone Regeneration

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Cell therapeutics offer significant regenerative potential, but effective delivery remains a challenge.
• Existing cell carriers often exhibit poor cytocompatibility and topological structures, leading to low cell viability during delivery.
• Developing advanced carriers is crucial for successful cell-based therapies.

Purpose of the Study:

• To develop novel porous shape-memory cryogel microspheres (CMS) for enhanced cell delivery.
• To optimize CMS pore size for improved cell viability and function.
• To evaluate the efficacy of CMS in delivering multiple cell types for functional tissue regeneration.

Main Methods:

• Methacrylated gelatin (GelMA) was used to prepare CMS via emulsion and gradient-cooling cryogelation.
• Pore size was controlled by adjusting the gradient-cooling time, with CMS-30 showing optimal pore size (15.5 ± 6.0 µm).
• Cell adhesion, proliferation, stemness, and protection during injection were assessed for human bone marrow stromal cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs).
• In vivo studies involved subcutaneous injection of mixed hBMSC- and HUVEC-loaded CMS-30 into nude mice.

Main Results:

• CMS demonstrated superior promotion of hBMSC and HUVEC adhesion and proliferation compared to hydrogel microspheres (HMS).
• Cells encapsulated in CMS maintained high stemness levels for 7 days and were protected during injection through a 26G needle.
• CMS-30 enhanced osteogenic differentiation of hBMSCs in vitro.
• In vivo, injected CMS-30 facilitated the formation of vascularized bone-like tissue, evidenced by high levels of OCN and CD31.

Conclusions:

• GelMA-based CMS with optimized pore sizes serve as effective carriers for delivering multiple cell types.
• These CMS protect cells during delivery and promote functional tissue regeneration, including vascularized bone formation.
• This study highlights the potential of CMS for advancing cell-based therapeutic strategies.