Engineering New Bone via a Minimally Invasive Route Using Human Bone Marrow-Derived Stromal Cell Aggregates, Microceramic Particles, and Human Platelet-Rich Plasma Gel

Abstract

Tissue Engineering Part A eering new bone via a minimally invasive route using human bone marrow derived stromal cell aggregates, micro ceramic particles and human platelet rich plasma gel (doi: 10.1089(doi: 10. /ten.TEA.2012 This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. 2 AbstractThere is a rise in the popularity of arthroscopic procedures in orthopedics. However, the majority of cell based bone tissue engineered constructs rely on solid pre-formed scaffolding materials, which require large incisions and extensive dissections for placement at the defect site. Thus, they are not suitable for minimally invasive techniques.The aim of this study was to develop a clinically relevant, easily moldable, bone tissue engineered construct (TEC), amenable to minimally invasive techniques, using human mesenchymal stromal cells (hMSC) and calcium phosphate micro particles in combination with an in-situ forming platelet rich plasma (PRP) gel obtained from human platelets. Most conventional TECs rely on seeding and culturing single cell suspensions of hMSCs on scaffolds. However, for generating TECs amenable to the minimally invasive approach, it was essential to aggregate the hMSCs in vitro prior to seeding them on the scaffolds as unaggregated MSCs did not generate any bone. 24 hours of in vitro aggregation was determined to be optimal for maintaining cell viability in vitro and bone formation in vivo. Moreover, no statistically significant difference was observed in the amount of bone formed when the TECs were implanted via an open approach or a minimally invasive route. TECs generated using MSCs from three different human donors generated new bone through the minimally invasive route in a reproducible manner, suggesting that these TECs could be a viable alternative to pre-formed scaffoldsemployed through an open surgery for treating bone defects. Page 2 of 35Tissue Engineering Part A eering new bone via a minimally invasive route using human bone marrow derived stromal cell aggregates, micro ceramic particles and human platelet rich plasma gel

Cell aggregation enhances bone formation by human mesenchymal stromal cells

“…The PRP gel itself is also an especially strong candidate for tissue engineering because it is patient-derived, chemical-free, a source of a plethora of growth factors, and can gel at a physiological temperature. Indeed, we recently demonstrated that it could be injected and gelled in situ (Chatterjea et al, 2013), and this work shows its promise for implantable bone tissue engineering.…”

“…Numerous animal studies and clinical trials have been performed to optimise the use of mesenchymal stromal cells (MSCs) for bone tissue engineering, with both revealing that the degree of bone formation is frequently inadequate (Chatterjea et al, 2010;Griffin et al, 2011;Meijer et al, 2008). One challenge is that while MSCs can be easily isolated from a variety of adult tissues and differentiated into multiple adult cell types including bone cells, their low frequency and limited propensity for osteogenic differentiation often necessitates in vitro expansion and pre-differentiation (Bruder et al, 1998;Friedenstein et al, 1966).…”

Delivery of Mesenchymal Stem Cells in Chitosan/Collagen Microbeads for Orthopedic Tissue Repair

“…This approach has recently been applied to a variety of tissues, including bone (Chatterjea et al, 2013; Dormer et al, 2012), cartilage (Cheng et al, 2011) and vasculature (Chen et al, 2013; Chamberlain et al, 2012). In the area of bone tissue engineering, a number of materials have been used in the modular format, including alginate (Man et al, 2012; Grellier et al, 2009), calcium phosphate (Jin et al, 2012) and composites (Zhou et al, 2011).…”

Application of platelet-rich plasma with stem cells in bone and periodontal tissue engineering

“…79 PRP contains various important GFs that enable the growth of bone and even though the mechanism of the bone regeneration is not well understood presently, its ease of handling and application makes it a good agent in the orthopedic field. 85 In addition, it reduces inflammation, provides excellent tissue healing and being autologous reduces the risk of disease transmission and immunogenic reactions. 81 …”