Implementing BMP-7 Chemically Modified RNA for Bone Regeneration with 3D Printable Hyaluronic Acid-Collagen Granular...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• RNA Therapeutics

Background:

• Chemically modified RNA (cmRNA) offers advantages over protein delivery and DNA gene therapy.
• Effective delivery systems are crucial for translating cmRNA technology into clinical applications, particularly for bone regeneration.
• Hyaluronic acid and collagen (THA-Col) hydrogels are biocompatible materials with potential for tissue engineering scaffolds.

Purpose of the Study:

• To develop and evaluate a 3D printable granular hydrogel (microgel) system based on THA-Col for delivering bone morphogenetic protein-7 cmRNA (BMP-7 cmRNA).
• To compare the performance of THA-Col microgels with bulk THA-Col gels regarding cmRNA transfection, cell viability, and osteogenic differentiation of human mesenchymal stromal cells (hMSCs).
• To assess the potential of BMP-7 cmRNA-loaded microgels as a bone graft substitute.

Main Methods:

• Fabrication of THA-Col granular hydrogels (microgels) by mechanical fragmentation of bulk gels.
• 3D printing of microgels for scaffold construction.
• In vitro assessment of BMP-7 cmRNA transfection efficiency in hMSCs using both microgels and bulk gels.
• Evaluation of cytotoxicity and cell viability of hMSCs cultured on microgels and bulk gels.
• Analysis of osteogenic differentiation of hMSCs, including alkaline phosphatase (ALP) production, on both gel types.

Main Results:

• Microgels exhibited higher cell viability compared to bulk THA-Col gels.
• Both microgels and bulk gels effectively supported BMP-7 cmRNA transfection.
• Human mesenchymal stromal cells cultured on microgels demonstrated significantly higher alkaline phosphatase (ALP) production during osteogenic differentiation compared to those on bulk gels.
• The developed microgel system is 3D printable and supports cellular functions relevant to bone regeneration.

Conclusions:

• THA-Col microgels represent a viable and effective platform for delivering BMP-7 cmRNA for bone regeneration.
• The microgel system demonstrates improved biocompatibility and osteogenic potential compared to bulk hydrogels.
• This approach holds significant promise for developing patient-specific bone graft substitutes, potentially overcoming limitations of autologous bone grafting and protein delivery.