Hydrogel Delivery of Mesenchymal Stem Cell-Expressing Bone Morphogenetic Protein-2 Enhances Bone Defect Repair.
BACKGROUND
The application of bone tissue engineering for repairing bone defects has gradually shown some satisfactory progress. One of the concerns raising scientific attention is the poor supply of growth factors. A number of growth factor delivery approaches have been developed for promoting bone formation. However, there is no systematic comparison of those approaches on efficiency of neobone formation. In this study, the approaches using periosteum, direct supply of growth factors, or gene transfection of growth factors were evaluated to determine the osteogenic capacity on the repair of bone defect.


METHODS
In total, 42 male 21-week-old Sprague-Dawley rats weighing 250 to 400 g were used as the bone defect model to evaluate the bone repair efficiency. Various tissue engineered constructs of poly(ethylene glycol)-poly(l-lactic acid) (PEG-PLLA) copolymer hydrogel with periosteum, with external supply of bone morphogenetic protein-2 (BMP2), or with BMP2-transfected bone marrow-derived mesenchymal stem cells (BMMSCs) were filled in a 7-mm bone defect region. Animals were euthanized at 3 months, and the hydrogel constructs were harvested. The evaluation with histological staining and radiography analysis were performed for the volume of new bone formation.


RESULTS
The PEG-PLLA scaffold with BMMSCs promotes bone regeneration with the addition of periosteum. The group with BMP2-transfected BMMSCs demonstrated the largest volume of new bone among all the testing groups.


CONCLUSIONS
Altogether, the results of this study provide the evidence that the combination of PEG-PLLA hydrogels with BMMSCs and sustained delivery of BMP2 resulted in the maximal bone regeneration.
Division of Microsurgery Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Ill.; and Research Service, Hines Veterans Administration Hospital, Hines, Ill.
Hui-Yi
HY
Hsiao
Division of Microsurgery Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Ill.; and Research Service, Hines Veterans Administration Hospital, Hines, Ill.
Shu-Rui
SR
Yang
Division of Microsurgery Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Ill.; and Research Service, Hines Veterans Administration Hospital, Hines, Ill.
Eric M
EM
Brey
Division of Microsurgery Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Ill.; and Research Service, Hines Veterans Administration Hospital, Hines, Ill.
I-Ming
IM
Chu
Division of Microsurgery Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Ill.; and Research Service, Hines Veterans Administration Hospital, Hines, Ill.
Ming-Huei
MH
Cheng