Abstract
Bone morphogenetic protein-2 (BMP-2) has been demonstrated to be one of the most vital osteogenic factors for bone augmentation. However, its uncontrolled administration has been associated with catastrophic side effects, which compromised its clinical use. To overcome these limitations, we aimed at developing a safer controlled and sustained release of BMP-2, utilizing poly(lactic-co-glycolic acid)-multistage vector composite microspheres (PLGA-MSV). The loading and release of BMP-2 from PLGA-MSV and its osteogenic potential in vitro and in vivo was evaluated. BMP-2 in vitro release kinetics was assessed by ELISA assay. It was found that PLGA-MSV achieved a longer and sustained release of BMP-2. Cell cytotoxicity and differentiation were evaluated in vitro by MTT and alkaline phosphatase (ALP) activity assays, respectively, with rat mesenchymal stem cells. The MTT results confirmed that PLGA-MSVs were not toxic to cells. ALP test demonstrated that the bioactivity of BMP-2 released from the PLGA-MSV was preserved, as it allowed for the osteogenic differentiation of rat mesenchymal stem cells, in vitro. The biocompatible, biodegradable, and osteogenic PLGA-MSVs system could be an ideal candidate for the safe use of BMP-2 in orthopedic tissue engineering applications.
Highlights
Autologous bone grafting remains the gold standard for spinal fusion, traumatic non-union and total hip arthroplasty complicated by osteolysis [1,2,3], yet it comes with morbidity and might provide insufficient volumes of bone for complex or multilevel reconstruction [4]
We demonstrated that PLGA-multistage vector (MSV) is able to efficiently load a growth factor (i.e., PDGF-BB) and release it in a controlled fashion in vivo, with a significant reduction of the initial burst release, while preserving its functionality [17]
The Bone morphogenetic protein-2 (BMP-2) loaded PLGA-MSV microspheres (10% and 20% w/v) containing 8 × 107 of MSV particles were dispersed into 0.5 mL of 1% BSA solution at 37 ◦C
Summary
Autologous bone grafting remains the gold standard for spinal fusion, traumatic non-union and total hip arthroplasty complicated by osteolysis [1,2,3], yet it comes with morbidity (separate incision, graft site pain, potential infection, etc.) and might provide insufficient volumes of bone for complex or multilevel reconstruction [4]. Bone morphogenetic protein-2 (BMP-2) is a transforming growth factor known to play a key role in the development and repair of bone and cartilage [5] It appeared to provide an ideal solution [6,7,8] to enhance bone growth but as its clinical use has expanded, multiple complications associated with BMP-2 use have come to light including local wound problems, chemical radiculitis, bony overgrowth into the canal or foramen, osteoclast activation with associated bony resorption and device displacement, and, possibly, cancer when used at very high doses in an off-label manner [1,9,10,11]. A new carrier system capable of sustained, regulated, local release of small but effective doses that do not impact BMP-2 functionality are needed to allow the avoidance of the biological complications associated with burst supraphysiologic dosing [16]
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