Abstract
Current clinical therapies for critical-sized bone defects (CSBDs) remain far from ideal. Previous studies have demonstrated that engineering bone tissue using mesenchymal stem cells (MSCs) is feasible. However, this approach is not effective for CSBDs due to inadequate vascularization. In our previous study, we have developed an injectable and porous nano calcium sulfate/alginate (nCS/A) scaffold and demonstrated that nCS/A composition is biocompatible and has proper biodegradability for bone regeneration. Here, we hypothesized that the combination of an injectable and porous nCS/A with bone morphogenetic protein 2 (BMP2) gene-modified MSCs and endothelial progenitor cells (EPCs) could significantly enhance vascularized bone regeneration. Our results demonstrated that delivery of MSCs and EPCs with the injectable nCS/A scaffold did not affect cell viability. Moreover, co-culture of BMP2 gene-modified MSCs and EPCs dramatically increased osteoblast differentiation of MSCs and endothelial differentiation of EPCs in vitro. We further tested the multifunctional bone reconstruction system consisting of an injectable and porous nCS/A scaffold (mimicking the nano-calcium matrix of bone) and BMP2 genetically-engineered MSCs and EPCs in a rat critical-sized (8 mm) caviarial bone defect model. Our in vivo results showed that, compared to the groups of nCS/A, nCS/A+MSCs, nCS/A+MSCs+EPCs and nCS/A+BMP2 gene-modified MSCs, the combination of BMP2 gene -modified MSCs and EPCs in nCS/A dramatically increased the new bone and vascular formation. These results demonstrated that EPCs increase new vascular growth, and that BMP2 gene modification for MSCs and EPCs dramatically promotes bone regeneration. This system could ultimately enable clinicians to better reconstruct the craniofacial bone and avoid donor site morbidity for CSBDs.
Highlights
Critical-sized bone defects (CSBDs) are the defects with the minimum length that cannot be spontaneously bridged and that should result in the formation of fibrous connective tissue rather than bone when left untreated [1]
Our results demonstrated that endothelial progenitor cells (EPCs) increase new vascular growth, and that bone morphogenetic protein 2 (BMP2) gene modification for mesenchymal stem cells (MSCs) and EPCs dramatically promotes vascularized bone regeneration
The results showed no significant differences in cell viability among those four groups, demonstrating that mixing and injecting MSCs and EPCs with the injectable nano calcium sulfate/alginate (nCS/A) scaffold does not affect cell viability and proliferation (Figure 2A)
Summary
Critical-sized bone defects (CSBDs) are the defects with the minimum length that cannot be spontaneously bridged and that should result in the formation of fibrous connective tissue rather than bone when left untreated [1]. Clinical therapies of CSBDs represent a great challenge for orthopedic and craniomaxillofacial surgeons, because current treatments rely on grafting materials such as autografts, allografts, xenografts, and alloplasts, while all those materials have specific limitations. Allografts are commonlyused grafting materials and are well documented in experimental and clinical studies [3]. Improved healing has been reported [4], clinical studies show limited new bone formation [5]. Allografts and xenografts carry the risk of pathogen transmission and immune rejection [6]. The life-long immune suppression required following their use is inconvenient to the patients and prone to complications. Alloplastic materials (alloplasts) are not biologically functional and carry the risk of long term foreign body reaction and associated complications [7]. Various other disadvantages such as multiple surgeries, facial scar formation, and non-union, significantly limit the repair of CSBDs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
