title: Nanophase bone substitute for craniofacial load bearing application: Pilot study in the rodent.
abstract: An exploratory pilot study shows that a rodent mandibular defect model is useful in determining the biological response to a nanophase collagen/apatite composite designed as a biomimetic load-bearing bone substitute. Using a critical size defect, eight groups of rats (n = 3) were implanted with four renditions of the nanophase bone substitute (NBS) biomaterial. Each rendition was tested with and without recombinant human bone morphogenetic protein 2 (BMP2). NBS biomaterial renditions were: baseline, hyper-densified, d-ribose crosslinked, and d-ribose crosslinked and hyper-densified. Biological outcomes were assessed surgically, radiologically, and histologically. With the limited power available due to the small N's involved, some interesting hypotheses were generated that will be more fully investigated in future studies. BMP2 loaded NBS, when uncrosslinked, resulted in robust bone formation in the entire defect volume (regardless of porosity). Unloaded NBS were well tolerated but did not cause significant new bone formation in the defect volume. Densification alone had little effect on in vivo performance. Crosslinking thwarted implant uptake of BMP2 and resulted in fibrous encapsulation. It is concluded that the nanophase bone substitute is well tolerated in this bone defect model. When loaded with BMP2, implantation resulted in complete bony healing and defect closure with implant density (porosity) having little effect on bone healing or remodeling. Without BMP2 the biomaterial did not result in defect closure. Crosslinking, necessary to increase mechanical properties in an aqueous environment, disrupts osteointegration and BMP2 uptake. Alternate implant fabrication strategies will be necessary to achieve an improved balance between material strength and osteointegration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 520-532, 2018.
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Case Western Reserve University, Cleveland, OH, USA.|Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Jonathan Z
authors.initials: JZ
authors.lastname: Baskin
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Soenjaya
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: James
authors.initials: J
authors.lastname: McMasters
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Henry Ford Hospital, Cleveland, OH, USA.
authors.forename: Alvin
authors.initials: A
authors.lastname: Ko
authors.affiliation: Image IQ, A Cleveland Clinic Innovation Company, Solon, OH, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Vasanji
authors.affiliation: Case Western Reserve University, Center for Clinical Investigations, Statistical Science Core, Cleveland, OH, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Morris
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Case Western Reserve University, Cleveland, OH, USA.|Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.|Department of Otolaryngology-Head and Neck Surgery and Facial Plastic and Reconstructive Surgery, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Eppell
mesh_terms: D000818:Animals; D001031:Apatites / Q000737:chemistry / Q000494:pharmacology; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000378:metabolism; D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology*; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D008334:Mandible; D008338:Mandibular Injuries; D053758:Nanoparticles; D010012:Osteogenesis / Q000187:drug effects; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012266:Ribose / Q000737:chemistry / Q000494:pharmacology; D016474:Weight-Bearing
chemical_list: D001031:Apatites; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D012266:Ribose; D003094:Collagen
keywords: animal model; bone substitute; collagen; craniofacial; pilot study