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Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats.

Tissue engineering. Part A (2015-01-30)
Johan van der Stok, Daniel Lozano, Yoke Chin Chai, Saber Amin Yavari, Angela P Bastidas Coral, Jan A N Verhaar, Enrique Gómez-Barrena, Jan Schrooten, Holger Jahr, Amir A Zadpoor, Pedro Esbrit, Harrie Weinans

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 (PTH)-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 100 nM solution for 24 h or left uncoated. Osteostatin-coated scaffolds contained ∼0.1 μg peptide/g titanium, and in vitro 81% was released within 24 h. Human periosteum-derived osteoprogenitor cells cultured on osteostatin-coated scaffolds did not induce significant changes in osteogenic (alkaline phosphatase [ALP], collagen type 1 [Col1], osteocalcin [OCN], runt-related transcription factor 2 [Runx2]), or angiogenic (vascular endothelial growth factor [VEGF]) gene expression; however, it resulted in an upregulation of osteoprotegerin (OPG) gene expression after 24 h and a lower receptor activator of nuclear factor kappa-B ligand (RankL):OPG mRNA ratio. In vivo, osteostatin-coated, porous titanium implants increased bone regeneration in 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±31 and 77±53 N·mm, not significant). 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.

Product Number
Product Description

Calcein-AM, BioReagent, suitable for fluorescence, ≥95.0% (HPLC)
Calcein AM solution, 4 mM in DMSO, ≥90% (HPLC), solution
Diethyl azodicarboxylate solution, 40 wt. % in toluene
Calcein-AM, Small Package (20 X 50 μg ), ≥95.0% (HPLC)
Ethidium homodimer, suitable for fluorescence, ~90% (HPCE)