title: Hydroxyapatite reinforced collagen scaffolds with improved architecture and mechanical properties.
abstract: Hydroxyapatite (HA) reinforced collagen scaffolds have shown promise for synthetic bone graft substitutes and tissue engineering scaffolds. Freeze-dried HA-collagen scaffolds are readily fabricated and have exhibited osteogenicity in vivo, but are limited by an inherent scaffold architecture that results in a relatively small pore size and weak mechanical properties. In order to overcome these limitations, HA-collagen scaffolds were prepared by compression molding HA reinforcements and paraffin microspheres within a suspension of concentrated collagen fibrils (∼ 180 mg/mL), cross-linking the collagen matrix, and leaching the paraffin porogen. HA-collagen scaffolds exhibited an architecture with high porosity (85-90%), interconnected pores ∼ 300-400 μm in size, and struts ∼ 3-100 μm in thickness containing 0-80 vol% HA whisker or powder reinforcements. HA reinforcement enabled a compressive modulus of up to ∼ 1 MPa, which was an order of magnitude greater than unreinforced collagen scaffolds. The compressive modulus was also at least one order of magnitude greater than comparable freeze-dried HA-collagen scaffolds and two orders of magnitude greater than absorbable collagen sponges used clinically. Moreover, scaffolds reinforced with up to 60 vol% HA exhibited fully recoverable elastic deformation upon loading to 50% compressive strain for at least 100,000 cycles. Thus, the scaffold mechanical properties were well-suited for surgical handling, fixation, and bearing osteogenic loads during bone regeneration. The scaffold architecture, permeability, and composition were shown to be conducive to the infiltration and differentiation of adipose-derive stromal cells in vitro. Acellular scaffolds were demonstrated to induce angiogenesis and osteogenesis after subcutaneous ectopic implantation by recruiting endogenous cell populations, suggesting that the scaffolds were osteoinductive.
authors: Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
authors: Robert J
authors: RJ
authors: Kane
authors: Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
authors: Holly E
authors: HE
authors: Weiss-Bilka
authors: Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
authors: Matthew J
authors: MJ
authors: Meagher
authors: Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
authors: Yongxing
authors: Y
authors: Liu
authors: Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
authors: Joshua A
authors: JA
authors: Gargac
authors: Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
authors: Glen L
authors: GL
authors: Niebur
authors: Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
authors: Diane R
authors: DR
authors: Wagner
authors: Department of Aerospace and Mechanical Engineering, Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: rroeder@nd.edu.
authors: Ryan K
authors: RK
authors: Roeder
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D016025:Bone Transplantation; D002417:Cattle; D003094:Collagen / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry*; D005615:Freezing; D006801:Humans; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D010232:Paraffin / Q000737:chemistry; D011208:Powders; D011312:Pressure; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D011208:Powders; D010232:Paraffin; D003094:Collagen; D017886:Durapatite
keywords: Bioactivity; Collagen; Hydroxyapatite; Osteoinduction; Scaffold