title: Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats.
abstract: 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.
authors: 1 Orthopaedic Research Laboratory, Department of Orthopaedics, Erasmus University Rotterdam Medical Centre , Rotterdam, The Netherlands .
authors: Johan
authors: J
authors: van der Stok
authors: Daniel
authors: D
authors: Lozano
authors: Yoke Chin
authors: YC
authors: Chai
authors: Saber
authors: S
authors: Amin Yavari
authors: Angela P
authors: AP
authors: Bastidas Coral
authors: Jan A N
authors: JA
authors: Verhaar
authors: Enrique
authors: E
authors: Gómez-Barrena
authors: Jan
authors: J
authors: Schrooten
authors: Holger
authors: H
authors: Jahr
authors: Amir A
authors: AA
authors: Zadpoor
authors: Pedro
authors: P
authors: Esbrit
authors: Harrie
authors: H
authors: Weinans
mesh_terms: D000293:Adolescent; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D016062:Porosity; D017208:Rats, Wistar; D014025:Titanium / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D020099:Coated Materials, Biocompatible; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; C071784:parathyroid hormone-related protein (107-111); D014025:Titanium