Effect of rhBMP‐2 and VEGF in a vascularized bone allotransplant experimental model based on surgical neoangiogenesis

Abstract

We have demonstrated survival of living allogeneic bone without long-term immunosuppression using short-term immunosuppression and simultaneous creation of an autogenous neoagiogenic circulation. In this study bone morphogenic protein-2 (rhBMP-2), and/or vascular endothelial growth factor (VEGF), were used to augment this process. Femoral diaphyseal bone was transplanted heterotopically from 46 Dark Agouti to 46 Lewis rats. Microvascular repair of the allotransplant nutrient pedicle was combined with intra-medullary implantation of an autogenous saphenous arteriovenous (AV) bundle and biodegradable microspheres containing buffer (control), rhBMP-2 or rhBMP-2 + VEGF. FK-506 given daily for 14 days maintained nutrient pedicle flow during angiogenesis. After an 18 weeks survival period, we measured angiogenesis (capillary density) from the AV bundle and cortical bone blood flow. Both measures were greater in the combined (rhBMP-2 + VEGF) group than rhBMP-2 and control groups (p<0.05). Osteoblast counts were also higher in the rhBMP-2 + VEGF group (p<0.05). A trend towards greater bone formation was seen in both rhBMP2 + VGF and rhBMP2 groups as compared to controls (p=0.059). Local administration of VEGF and rhBMP-2 augments angiogenesis, osteoblastic activity and bone blood flow from implanted blood vessels of donor origin in vascularized bone allografts.

Emulating native periosteum cell population and subsequent paracrine factor production to promote tissue engineered periosteum-mediated allograft healing

“…periosteum modified allografts was investigated within the context of a murine femur segmental defect model [4, 10–12]. Vascularization was examined as it is critical in the initiation of graft healing, and has been shown to be influenced by periosteal VEGF and BMP2 signaling, as well as other paracrine factors [24, 47, 74, 75]. To investigate the efficacy of transplanted MSCs on initiating this healing cascade, host-mediated vascular infiltration was assessed 6 and 9 weeks following implantation using contrast enhanced vascular perfusion and subsequent μCT-based reconstruction techniques (Fig.…”

Effects of Surgical Angiogenesis on Segmental Bone Reconstruction With Cryopreserved Massive‐Structural Allografts in a Porcine Tibia Model

“…Others have reported similar remodeling when a periosteal sleeve was left behind to envelop an orthotopically placed allograft . The angiogeneic effect has been demonstrated to be amplified with the use of growth factors when delivered by osmotic pumps, biodegradable microspheres or endothelial cell transfection (gene therapy) . Such surgical angiogenesis may prove of value in improving outcomes for many patients in whom cryopreserved bone segments are used to span large segmental gaps resulting from limb‐sparing tumor surgery, trauma, congenital deformity or osteomyelitis.…”

Polymeric microspheres: a delivery system for osteogenic differentiation

“…[35] Co-delivery of BMP-2 and VEGF GFs in PLGA MSs resulted in higher bone formation due to the presence of VEGF, which was found efficient for angiogenesis and bone blood flow. [36] Similarly, VEGF-encapsulated PLGA MS enhanced angiogenesis and osteogenesis at 4 weeks postadministration, which increased cortical bone flow as well as bone turnover compared with FGF2 and combination of VEGF and FGF2. [37,38] TGF and BMP-2-encapsulated MSs of PLGA and PLGA/HA showed different release behavior with the treatment of ethylene oxide (EO), ethanol (EtOH), EO with carbon dioxide, and EO with EtOH separately.…”

“…Therefore, the formation of bone and cartilage is more in silk scaffold . Co‐delivery of BMP‐2 and VEGF GFs in PLGA MSs resulted in higher bone formation due to the presence of VEGF, which was found efficient for angiogenesis and bone blood flow . Similarly, VEGF‐encapsulated PLGA MS enhanced angiogenesis and osteogenesis at 4 weeks postadministration, which increased cortical bone flow as well as bone turnover compared with FGF2 and combination of VEGF and FGF2 .…”