Implementing BMP‐7 Chemically Modified RNA for Bone Regeneration with 3D Printable Hyaluronic Acid‐Collagen Granular Gels
Advanced Healthcare Materials, vol. 14, pp. e2405047
Abstract
Chemically modified RNA (cmRNA) is emerging as a more effective alternative to protein delivery and DNA-based gene therapy. To implement this technology for bone regeneration, a suitable biomaterial functioning as scaffold and delivery system is necessary. This study introduces a 3D printable granular hydrogel consisting of hyaluronic acid and collagen (THA-Col) for the delivery of bone morphogenetic protein (BMP)-7 cmRNA as activated matrix to promote bone healing. Granular hydrogels are produced by mechanically fragmenting bulk THA-Col gels. Resulting microgels are 3D printable and are further investigated in comparison to bulk THA-Col gels for BMP-7 cmRNA transfection efficiency, cytotoxicity, and osteogenic differentiation of human mesenchymal stromal cells (hMSCs). Microgels showed higher cell viability than bulk gels, while both bulk and microgels could support transfection with BMP-7. During in vitro osteogenic differentiation, hMSCs on microgels showed higher production of alkaline phosphatase (ALP) compared to bulk gels. The combination of microgels loaded with BMP-7 cmRNA introduced in this work holds significant potential toward the development of patient-specific bone graft substitutes to replace autologous bone grafting and protein delivery.
Authors 7
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Affiliation as printed
Department of Cell Biology‐Inspired Tissue Engineering MERLN Maastricht University Maastricht 6229 ER the Netherlands
Department of Cell Biology-Inspired Tissue Engineering, MERLN, Maastricht University, Maastricht, 6229 ER the Netherlands
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Affiliation as printed
AO Research Institute Davos Davos Platz 7270 Switzerland
AO Research Institute Davos, Davos Platz, 7270 Switzerland
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Affiliation as printed
Ethris GmbH 82152 Planegg Germany
Ethris GmbH, 82152 Planegg, Germany
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Affiliation as printed
Department of Cell Biology‐Inspired Tissue Engineering MERLN Maastricht University Maastricht 6229 ER the Netherlands
Department of Cell Biology-Inspired Tissue Engineering, MERLN, Maastricht University, Maastricht, 6229 ER the Netherlands
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Experimental Orthopaedics and Trauma Surgery RWTH Aachen University Hospital 52074 Aachen Germany
Experimental Orthopaedics and Trauma Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany
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Affiliation as printed
AO Research Institute Davos Davos Platz 7270 Switzerland
AO Research Institute Davos, Davos Platz, 7270 Switzerland
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Matteo D’Este corresponding
Affiliation as printed
AO Research Institute Davos Davos Platz 7270 Switzerland
AO Research Institute Davos, Davos Platz, 7270 Switzerland
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