title: Repair of large cranial defects by hBMP-2 expressing bone marrow stromal cells: comparison between alginate and collagen type I systems.
abstract: Despite a wide range of available sources for bone repair, significant limitations persist. To bioengineer bone, we have previously transferred adenovirus-mediated human BMP-2 gene into autologous bone marrow stromal cells (MSC). We have successfully repaired large, full thickness, cranial defects using this approach. We report now the effectiveness of various hydrogels as the scaffold for this type of bone regeneration, comparing specifically alginate with Type I collagen. Cultured MSC of miniature swine were infected with BMP-2 or beta-gal adenovirus 7 days before implantation. These cells were mixed with alginate, ultrapure alginate, alginate-RGD, or type I collagen to fabricate the MSC/biomaterial constructs. The results of cranial bone regeneration were assessed by gross examination, histology, 3D CT, and biomechanical tests at 6 weeks and 3 months after implantation. We found that the BMP-2 MSC/collagen type I construct, but not the beta-gal control, effectively achieved nearly complete repair of the cranial defects. No bone regeneration was observed with the other hydrogels. Biomechanical testing showed that the new bone strength was very close and only slightly inferior to that of normal cranial bone. Controlling for the integration of stem cells and ex vivo gene transfer, the alginate scaffolds has a significant negative impact on the success of the construct. Our study demonstrates better bone regeneration by collagen type I over alginate. This may have therapeutic implications for tissue engineered bone repair.
authors.affiliation: Department of Plastic Surgery, China Medical University Hospital, Taichung 404, Taiwan.
authors.forename: Sophia Chia Ning
authors.initials: SC
authors.lastname: Chang
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Chung
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Tai
authors.forename: Philips Kuo Ting
authors.initials: PK
authors.lastname: Chen
authors.forename: Tsung-Min
authors.initials: TM
authors.lastname: Lin
authors.forename: Long-Bin
authors.initials: LB
authors.lastname: Jeng
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000464:Alginates / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D001861:Bone Regeneration / Q000502:physiology*; D017690:Cell Transplantation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism*; D019245:Compressive Strength; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020007:Implants, Experimental; D008422:Materials Testing; D012886:Skull / Q000473:pathology / Q000502:physiology / Q000601:surgery; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*; D013552:Swine; D023822:Tissue Engineering / Q000379:methods; D014945:Wound Healing
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D006603:Hexuronic Acids; D020723:Glucuronic Acid