Strontium Hydroxyapatite scaffolds engineered with stem cells aid osteointegration and osteogenesis in osteoporotic sheep model

Abstract Osteoporotic fracture healing is an orthopaedic challenge due to excessive bone resorption and impaired osteogenesis. Majority of current treatment strategies focus on regulating bone resorption and the potential application of Mesenchymal Stem Cells (MSCs) in promoting osteogenesis has not been explored much. Furthermore, the present study has put forth a novel approach, wherein the synergistic action of Strontium (Sr) and MSCs in a single implant may facilitate osteoporotic bone healing. Strontium Hydroxyapatite (SrHA) synthesized by wet precipitation was fabricated into tissue engineered Strontium incorporated Hydroxyapatite (cSrHA) using sheep adipose tissue derived MSCs (ADMSCs). Porosity, radiopacity and cytocompatibility of SrHA scaffolds were found appropriate for orthopaedic applications. cSrHA scaffolds exhibited an in vitro Alkaline Phosphatase activity of 20 μmol pnp/30 min comparable to that of Hydroxyapatite (HA) – control scaffold, proving its osteogenic efficacy. Implantation studies in sheep osteoporotic model depicted enhanced osteogenic ability with mature lamellar bone formation in cSrHA implanted group, compared to bare HA, SrHA and tissue engineered HA implanted groups. Histomorphometry data substantiated improved osteogenesis on par with material resorption, as cSrHA implanted group exhibited highest regeneration ratio of 0.38 ± 0.05. Density histograms from micro CT further signified the enhanced osteointegrative ability of cSrHA implants. Results of the study depicted the therapeutic potential of cSrHA in osteoporotic bone healing and proposes the use of allogenic ADMSCs for fabricating “Off the Shelf Tissue Engineered Products”.