Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats
van der Stok, Johan × Lozano, Daniel Chai, Yoke Chin Amin Yavari, Saber Bastidas Coral, Angela P Verhaar, Jan Gomez-Barrena, Enrique Schrooten, Jan Jahr, Holger Zadpoor, Amir A Esbrit, Pedro Weinans, Harrie #
Mary Ann Liebert Inc
Tissue Engineering Part A vol:21 issue:9-10 pages:1495-506
A promising bone graft substitute is porous titanium. Porous titanium, produced by selective laser melting (SLM), can be made as a completely open porous and load-bearing scaffold that facilitates bone regeneration through osteoconduction. In this study, the bone regenerative capacity of porous titanium is improved with a coating of osteostatin, an osteoinductive peptide that consists of the 107-111 domain of the parathyroid hormone-related protein (PTHrP) and the effects of this osteostatin-coating on bone regeneration were evaluated in vitro and in vivo. SLM-produced porous titanium received an alkali-acid-heat treatment and was coated with osteostatin through soaking in a 100nM solution for 24h or left uncoated. Osteostatin-coated scaffolds contained ~0.1µg peptide/g titanium, and in vitro 81% was released within 24h. Human periosteum-derived osteoprogenitor cells cultured on osteostatin coated scaffolds did not induce significant changes in osteogenic (ALP, Col1, OCN, Runx2) or angiogenic (VEGF) gene expression, however it resulted in an upregulation of OPG gene expression after 24h and a lower RankL:OPG mRNA ratio. In vivo, osteostatin-coated porous titanium implants increased bone regeneration critical-sized cortical bone defects (p=0.005). . Bone regeneration proceeded until 12 weeks and femurs grafted with osteostatin-coated implants and uncoated implants recovered respectively 66% and 53% of the original femur torque strength (97±31N.mm and 77±53N.mm, NS). In conclusion, the osteostatin-coating improved bone regeneration of porous titanium. This effect was initiated after a short burst-release, and might be related to the observed in vitro upregulation of OPG gene expression by osteostatin in osteoprogenitor cells. Long-term beneficial effects of osteostatin-coated porous titanium implants on bone regeneration or mechanical strength were not established here and may require optimization of the pace and dose of osteostatin release.