title: Principles of tissue engineering applied to programmable osteogenesis.
abstract: This article presents a strategy for design, engineering, and fabrication of a bioresorbable, manufactured bone graft substitute (BGS) device. The approach is based on established precepts of osteogenesis, molecular biology of hyaluronic acid and osteoinductive proteins, and theoretical preformance criteria for such a device collated from the literature of 1991 to 1996. Application of this design and engineering strategy results in a composite device consisting of a D,D-L,L-polylactic acid macrostructure optimized to the architecture of cancellous bone, a microstructure composed of a filamentous velour of hyaluronan and a recombinant human bone morphogenetic protein 2 (rhBMP-2). The performance of this construct was tested in vivo in the dog, intertransverse process, spinal fusion model and in a critical sized defect of the rabbit radius. Data from these studies are used to illustrate principle points of the design and engineering concept.
authors.affiliation: THM Biomedical, Inc., Duluth, Minnesota 55802, USA. jhbdlh@cpinternet.com
authors.forename: J H
authors.initials: JH
authors.lastname: Brekke
authors.forename: J M
authors.initials: JM
authors.lastname: Toth
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D018786:Bone Substitutes; D001842:Bone and Bones / Q000033:anatomy & histology / Q000166:cytology; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004738:Engineering; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000502:physiology; D019344:Lactic Acid / Q000494:pharmacology; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D010641:Phenotype; D011091:Polyesters; D011108:Polymers / Q000494:pharmacology; D011817:Rabbits; D013123:Spinal Fusion; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D006820:Hyaluronic Acid