A Platelet-Rich Plasma-Based Membrane as a Periosteal Substitute with Enhanced Osteogenic and Angiogenic Properties: A New Concept for Bone Repair

Abstract

The periosteum plays a pivotal role during bone development and repair contributing to bone vascularization and osteoprogenitor cells source. We propose a periosteal substitute engineered using a platelet-rich plasma (PRP) membrane incorporating autologous bone marrow-derived mesenchymal stem cells (PRP/BMSC gel membrane) to be wrapped around an osteoconductive scaffold for regeneration of compromised bone defects. The PRP/BMSC gel membrane was optimized using different compositions for optimal release of vascular endothelial growth factor (VEGF) and platelet derived growth factor-BB (PDGF-BB). Survival and proliferation of cells in the PRP gel membrane with time were confirmed in addition to their osteogenic capacity. Furthermore, to evaluate the possible effects of the PRP/BMSC gel membrane on surrounding progenitor cells in the injury area, we found that the PRP gel membrane products could significantly induce the migration of human endothelial cells in vitro, and increased the expression of bone morphogenetic protein 2 in cultured BMSC. These cells also secreted significant amounts of soluble proangiogenic factors, such as PDGF-BB, VEGF, and interleukin-8 (IL-8). Finally, the functionality of the PRP/BMSC gel membrane periosteal substitute for bone regeneration was tested in vivo both in an ectopic mouse model as well as in a rabbit segmental bone defect model providing evidence of its capacity to biomimic a periosteal response enhancing bone regeneration.

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…Mouse: [223] (hVEGF/hMPC), [224] (hVEGF/hBMP2/hMPC) Rat: [225] (hBMP2/hMPC), [226] (hBMP7/hMPC) Rabbit: [227], [228] (PRP/rbMPC),…”

Tissue engineered bone using select growth factors: A comprehensive review of animal studies and clinical translation studies in man

“…A number of studies have investigated combination treatment with PDGF and several other growth factors including bFGF (Meraw et al, 2000), BMP-2 (Martino et al, 2011), BMP-7 (Zhang et al, 2009b, IGF-1 (Nociti Junior et al, 2000), osteogenin (Marden et al, 1993), TGF-β1 and VEGF (El Backly et al, 2013). Bone formation was reported to increase between 1.4 and 2.3 fold (Zhang et al, 2009b) within large animals (dog (Zhang et al, 2009b)) following PDGF dosages around 5 µg/mL for direct administration (Nociti Junior et al, 2000), or 2 x 10 10 / mL viral particles for indirect administration (Zhang et al, 2009b).…”

“…Bone formation was reported to increase between 1.4 and 2.3 fold (Zhang et al, 2009b) within large animals (dog (Zhang et al, 2009b)) following PDGF dosages around 5 µg/mL for direct administration (Nociti Junior et al, 2000), or 2 x 10 10 / mL viral particles for indirect administration (Zhang et al, 2009b). Combination treatments within small animal (mouse (El Backly et al, 2013), rabbit and rat (Park et al, 2013)) studies reported increased bone formation between 2.5 (Xu D Gothard et al Tissue engineered bone and clinical translation et al, 2012) and 10 fold following PDGF dosages ranging between 0.05 (Martino et al, 2011) and 200 µg (Marden et al, 1993).…”

Transplanted Umbilical Cord Mesenchymal Stem Cells Modify the In Vivo Microenvironment Enhancing Angiogenesis and Leading to Bone Regeneration

“…These scaffolds have been shown to support orthotopic bone formation in a rabbit model [2]. Immediately before surgery, 2.5 · 10 6 UC-MSCs were loaded onto the scaffolds and embedded in a fibrin glue (Tissucol; Baxter).…”

“…The implantation of these cells combined with ceramic-based biomaterials in bone defects gives the best results in terms of bone formation both in animal models [2,3] and in patients [4]. Although BM-MSCs are a feasible and autologous source of MSCs, their painful and invasive collection method has limited their use.…”