The repair of large bone defects such as segmental defects in the long bones of the limbs is a challenging clinical problem. enhanced new bone formation to 46% 57 and 45% respectively. New bone formation in scaffolds pretreated for 1 3 and 6 days and loaded with bone morphogenetic protein-2 (BMP-2) (1 μg/defect) was 65% 61 and 64% respectively. The results show that converting a surface layer of the glass to hydroxyapatite or loading the surface-treated scaffolds with BMP-2 can significantly improve the capacity of 13-93 bioactive glass scaffolds to regenerate bone in an osseous defect. Based on their mechanical properties evaluated previously and their capacity to regenerate bone found in this study these CPI-203 13-93 bioactive glass scaffolds pretreated or loaded with BMP-2 are promising in structural bone repair. Keywords: bone regeneration bioactive glass scaffold surface modification bone morphogenetic protein-2 rat calvarial defect model 1 Introduction The repair of large bone defects is a challenging clinical problem . While contained bone defects are repairable with commercially-available osteoconductive and osteoinductive filler materials [2 3 there is no ideal biological solution to reconstitute structural bone loss such as segmental defects in the long bones of the limbs. Available treatments such as bone allografts autografts porous metals and bone cement have limitations related to costs availability longevity donor site morbidity and uncertain healing to host bone. Consequently there is a great need for porous biocompatible implants that can replicate the structure and function of bone and have the requisite mechanical properties for reliable long-term cyclical loading during weight bearing. As described previously [4-6] bioactive glasses have several attractive properties as a scaffold material for bone repair such as their biocompatibility ability to convert in vivo to hydroxyapatite (the mineral constituent of bone) and ability to bond strongly to hard CPI-203 tissue. Some bioactive glasses such as the silicate glass designated 45S5 also have the ability to bond to soft tissue [5 6 Most previous studies have targeted bioactive glass scaffolds with relatively low strength three-dimensional (3D) architectures such as strengths in the range of human trabecular bone (2-12 MPa) . Recent studies have shown that silicate bioactive glass scaffolds (13-93 and 6P53B) created by solid freeform fabrication techniques such as freeze extrusion fabrication  and robocasting [9 10 have compressive strengths (~140 MPa) comparable to human cortical bone (100-150 MPa) . Our recent work showed that strong porous bioactive glass (13-93) scaffolds created using robocasting had excellent mechanical reliability (Weibull modulus = 12) and promising fatigue resistance under cyclic CPI-203 stresses far greater than normal physiological stresses  but the capacity of those strong porous bioactive glass (13-93) scaffolds to regenerate bone has not yet been studied. Our recent studies also showed that the elastic (brittle) mechanical response of the 13-93 bioactive glass scaffolds in vitro changed to an “elasto-plastic” response after implantation for longer than 2-4 weeks in vivo as a result of soft and hard tissue growth into the pores of the scaffolds [11 12 However concerns still remain about the low fracture toughness flexural strength and torsional strength of the as-fabricated bioactive glass scaffolds. In addition to material composition and microstructure  scaffold healing to bone in vivo can be markedly affected by other variables such as surface composition and structure the release of osteoinductive growth factors and the presence (or absence) of living cells. Interconnected pores of size 100 μm are recognized as the minimum requirement for supporting Rabbit Polyclonal to GPR132. tissue ingrowth  but pores of size 300 μm or larger may be required for enhanced bone ingrowth and capillary formation . Surface modification of macroporous bioactive glass scaffolds have targeted the creation of fine pores (nanometers to a few microns in size) to modify the surface roughness and increase the surface area of the scaffolds [16-18]. Conversion of a surface layer to HA by reaction in an aqueous phosphate solution has been shown to improve the capacity of borate and silicate CPI-203 bioactive glass to support cell.