Bone Morphogenetic Protein-2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels

Autor: Eben Alsberg, J. Kent Leach, Motasem Refaat, Steve S. Ho, Nina L. Vollmer, Mark A Lee, Oju Jeon
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Cell
Nude
Medical Biotechnology
Pharmaceutical Science
Bone Morphogenetic Protein 2
Apoptosis
Biocompatible Materials
02 engineering and technology
Regenerative Medicine
Glucuronic Acid
Stem Cell Research - Nonembryonic - Human
Osteogenesis
mesenchymal stem cell
Cells
Cultured

Cultured
Hexuronic Acids
Cell Differentiation
Hydrogels
021001 nanoscience & nanotechnology
Cell biology
medicine.anatomical_structure
Self-healing hydrogels
Stem Cell Research - Nonembryonic - Non-Human
photocrosslinking
Development of treatments and therapeutic interventions
0210 nano-technology
Materials science
Alginates
Cell Survival
Cells
Biomedical Engineering
Bioengineering
Bone healing
Bone morphogenetic protein 2
survival
Bone and Bones
Article
osteogenesis
Biomaterials
03 medical and health sciences
Medicinal and Biomolecular Chemistry
Rats
Nude

medicine
Bioluminescence imaging
Animals
Humans
Transplantation
5.2 Cellular and gene therapies
Tissue Engineering
Mesenchymal stem cell
Mesenchymal Stem Cells
Stem Cell Research
Rats
030104 developmental biology
Musculoskeletal
bone morphogenetic protein-2
Biomedical engineering
Zdroj: Advanced healthcare materials, vol 5, iss 19
ISSN: 2192-2659
Popis: There is a substantial need for methods that prolong cell persistence and enhance functionality in situ to enhance cell-based tissue repair. Bone morphogenetic protein-2 (BMP-2) is often used at high concentrations for osteogenic differentiation of mesenchymal stem cells (MSCs) but can induce apoptosis. Biomaterials facilitate the delivery of lower doses of inductive molecules, potentially reducing side effects and localizing materials at the target site. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular-sized bone defects, providing improved control over material degradation compared to ionically-crosslinked hydrogels. We hypothesized that the delivery of human MSCs and BMP-2 from a PAH would increase cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP-2. BMP-2 significantly decreased apoptosis and enhanced survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging revealed increased MSC survival when implanted in BMP-2 PAHs over 4 weeks. Bone defects treated with MSCs in BMP-2 PAHs demonstrated 100% union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC-entrapped PAHs alone did not fully bridge. This study demonstrates that transplantation of MSCs with BMP-2 in PAHs achieves robust bone healing, providing a promising platform for use in bone repair.
Databáze: OpenAIRE