Background Reconstruction of a segmental fracture with massive bone loss is

Background Reconstruction of a segmental fracture with massive bone loss is still a challenge for orthopaedic surgeons. pH changes during hydrolytic degradation cell toxicity and the release profile of BMP-2 were also evaluated and/or were compared with those of a well-characterized mPEG-PLGA copolymer. In animal testing rabbits (n?=?36) that received critically sized (10?mm) femoral defects were divided into 6 groups. These experimental groups included an untreated group autograft and groups treated with the synthesized copolymer carrying different concentrations of BMP-2 (0 5 10 and 20?μg/ml). Bone repair was evaluated using X-ray radiography histological staining micro-computed tomography (μCT) biomarker examination and biomechanical testing in a 12-week treatment period. Results A new thermosensitive mPEG-PLGA/Box/mPEG-PLGA block copolymer or named as BOX copolymer was successfully prepared. Compared to the reported mPEG-PLGA in vitro the prepared BOX copolymer at the same weight percent concentrations exhibited wider temperature ranges of gelation slower degradation rates higher the pH values as MLN8237 well as less cytotoxicity. Furthermore the BMP-2 release from BOX hydrogel exhibited a near-linear release profile in vitro. In animal experiments treatment of critical-sized bony defects with 25?wt% BOX hydrogel carrying BMP-2 effectively promoted fracture healing during the 12-week trial period and higher concentrations of BMP-2 treatment correlated MLN8237 with better bone quality. Most importantly clinical outcome and bone healing in the BOX-hydrogel group with 20?μg/ml BMP-2 were nearly equivalent to those in the autograft group in a 12-week treatment course. Conclusion These data support that the use of BOX hydrogel (25?wt%) as a drug delivery system is a promising method in the treatment of large bone defects. HSPC150 class=”kwd-title”>Keywords: Biodegradable polymer Thermosensitive hydrogel mPEG-PLGA Fracture healing BMP-2 Background Reconstruction of massive segmental bone defects caused by MLN8237 trauma or tumor is still a significant clinical challenge. Unsatisfactory clinical outcomes occur in more than 30?% of patients with high-energy fracture after surgical treatment [1]. Thus far there are a variety of interventions available to orthopedic surgeons to manage extensive local bone loss including autograft allograft MLN8237 and transplantation with synthetic bone substitutes. Autograft also known as autologous bone graft is considered to be a gold standard for bone replacement. Although the use of autograft is considered as the gold standard some problems are encountered such as donor site morbidity and limited donor bone supply [2 3 Allograft is an alternative way MLN8237 for bone regeneration in which the graft bone is obtained from another individual. Several disadvantages have been reported for allograft transplantation including incomplete or delayed graft incorporation poor osteoinductivity the potential for eliciting a deleterious immune response and the risk of disease MLN8237 transmission [4 5 To circumvent these problems of autograft and allograft various synthetic bone substitutes such as hydroxyapatite calcium phosphate cements or biodegradable polymers have been developed [6-8]. These synthetic bone substitutes provide the benefits including availability sterility and reduced morbidity at the graft site. Theoretically an ideal bone graft material should include four characteristics: (i) osteointegration the ability to directly bond to the surface of host bone; (ii) osteoconduction the ability to serve as a scaffold to guide the growth of bone; (iii) osteoinduction the ability to stimulate differentiation of osteoprogenitor cells into osteoblasts; (iv) osteogenesis the formation of new bone by osteoblasts present within the graft material [9]. Based on criteria in the list only autograft matches all of these requirements while allograft possesses osteointegrative osteoconductive and osteoinductive potentials. Currently synthetic bone substitutes possess only osteointegrative and osteoconductive properties. Due to the lack of osteoinductive and osteogenic abilities one possible approach to improving synthetic bone substitutes is to incorporate bone morphogenetic protein 2 (BMP-2) the most common cellular osteoinductive mediator that has received FDA approval for the use in treating acute tibial fractures [10]. In addition to exogenous BMP-2 treatment stem.