title: Bone Morphogenetic Protein-2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels.
abstract: There is a substantial need to 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 BMP-2, reducing side effects and localizing materials at target sites. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular-sized bone defects, providing improved control over material degradation compared to ionically cross-linked hydrogels. It is hypothesized that the delivery of MSCs and BMP-2 from a PAH increases cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP-2. BMP-2 significantly decreases apoptosis and enhances survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging reveals increased MSC survival when implanted in BMP-2 PAHs. Bone defects treated with MSCs in BMP-2 PAHs demonstrate 100% union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC-entrapped PAHs alone do not fully bridge. This study demonstrates that transplantation of MSCs with BMP-2 in PAHs achieves robust bone healing, providing a promising platform for bone repair.
authors: Department of Biomedical Engineering, University of California, Davis 451 Health Sciences Drive, Davis, CA, 95616, USA.
authors: Steve S
authors: SS
authors: Ho
authors: Department of Biomedical Engineering, University of California, Davis 451 Health Sciences Drive, Davis, CA, 95616, USA.
authors: Nina L
authors: NL
authors: Vollmer
authors: Department of Orthopaedic Surgery, School of Medicine, University of California, Davis, Sacramento, CA, 95817, USA.
authors: Motasem I
authors: MI
authors: Refaat
authors: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors: Oju
authors: O
authors: Jeon
authors: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.|Department of Orthopaedic Surgery, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors: Eben
authors: E
authors: Alsberg
authors: Department of Orthopaedic Surgery, School of Medicine, University of California, Davis, Sacramento, CA, 95817, USA.
authors: Mark A
authors: MA
authors: Lee
authors: Department of Biomedical Engineering, University of California, Davis 451 Health Sciences Drive, Davis, CA, 95616, USA. jkleach@ucdavis.edu.|Department of Orthopaedic Surgery, School of Medicine, University of California, Davis, Sacramento, CA, 95817, USA. jkleach@ucdavis.edu.
authors: J Kent
authors: JK
authors: Leach
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011923:Rats, Nude; D023822:Tissue Engineering / Q000379:methods
chemical_list: D000464:Alginates; C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D006603:Hexuronic Acids; D020100:Hydrogels; D020723:Glucuronic Acid
keywords: bone morphogenetic protein-2; mesenchymal stem cell; osteogenesis; photocrosslinking; survival