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Dual Delivery of BMP2 and IGF1 Through Injectable Hydrogel Promotes Cranial Bone Defect Healing

 YoungBum Park  ;  Sien Lin  ;  Yan Bai  ;  Seyedsina Moeinzadeh  ;  Sungwoo Kim  ;  Jianping Huang  ;  Uilyong Lee  ;  Ngan Fong Huang  ;  Yunzhi Peter Yang 
 TISSUE ENGINEERING PART A, Vol.28(17-18) : 760-769, 2022-09 
Journal Title
Issue Date
Alginates / pharmacology ; Animals ; Bone Morphogenetic Protein 2* / pharmacology ; Bone Regeneration ; Hydrogels* / chemistry ; Hydrogels* / pharmacology ; Insulin-Like Growth Factor I / pharmacology ; Polyethylene Glycols / chemistry ; Polyethylene Glycols / pharmacology ; Rats ; Rats, Sprague-Dawley ; Skull / pathology ; X-Ray Microtomography
bone formation ; bone morphogenetic protein ; craniomaxillofacial bone defect ; hydrogel ; insulin-like growth factor
Critical-sized cranial bone defect remains a great clinical challenge. With advantages in regenerative medicine, injectable hydrogels incorporated with bioactive molecules show great potential in promoting cranial bone repair. Recently, we developed a dual delivery system by sequential release of bone morphogenetic protein 2 (BMP2) followed by insulin-like growth factor 1 (IGF1) in microparticles (MPs), and an injectable alginate/collagen (alg/col)-based hydrogel. In this study, we aim to evaluate the effect of dual delivery of BMP2 and IGF1 in MPs through the injectable hydrogel in critical-sized cranial bone defect healing. The gelatin MPs loaded with BMP2 and poly(lactic-co-glycolic acid)-poly(ethylene glycol)-carboxyl (PLGA-PEG-COOH) MPs loaded with IGF1 were prepared, respectively. The encapsulation efficiency and release profile of growth factors in MPs were measured. A cranial defect model was applied to evaluate the efficacy of the dual delivery system in bone regeneration. Adult Sprague Dawley rats were subjected to osteotomy to make an ⌀8-mm cranial defect. The injectable hydrogel containing MPs loaded with BMP2 (2 μg), IGF1 (2 μg), or a combination of BMP2 (1 μg) and IGF1 (1 μg) were injected to the defect site. New bone formation was evaluated by microcomputed tomography, histological analysis, and immunohistochemistry after 4 or 8 weeks. Data showed that dual delivery of the low-dose BMP2 and IGF1 in MPs through alg/col-based hydrogel successfully restored cranial bone as early as 4 weeks after implantation, whose effect was comparable to the single delivery of high-dose BMP2 in MPs. In conclusion, this study suggests that dual delivery of BMP2 and IGF1 in MPs in alg/col-based hydrogel achieves early bone regeneration in critical-sized bone defect, with advantage in reducing the dose of BMP2. Impact Statement Sequential release of bone morphogenetic protein 2 (BMP2) followed by insulin-like growth factor 1 (IGF1) in two different microparticles promotes critical-sized bone defect healing. This dual delivery system reduces the dose of BMP2 by supplementing IGF1, which may diminish the potential side effects of BMP2.
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2. College of Dentistry (치과대학) > Dept. of Prosthodontics (보철과학교실) > 1. Journal Papers
Yonsei Authors
Park, Young Bum(박영범)
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