title: Short-term immunosuppression and surgical neoangiogenesis with host vessels maintains long-term viability of vascularized bone allografts.
abstract: Currently available methods to reconstruct large skeletal defects have limitations. These include nonunion and stress fractures in structural allografts, and inability to match the size, shape, and/or strength of most recipient sites using vascularized fibular autografts. Prosthetic diaphyseal replacements may loosen or produce periprosthetic fractures. Transplantation of living allogenic bone would enable matching donor bone to the recipient site, combined with the desirable healing and remodeling properties of living bone. We propose a novel method by which the transplantation of such tissue might be done without the risks of life-long immunosuppression, using surgical neoangiogenesis to develop a new host-derived osseous blood supply. We performed vascularized femoral allografts from 86 female Dark Agouti donor rats to male Piebald Virol Glaxo recipients across a major histocompatibility (MHC) barrier. In addition to microvascular reconstruction of the nutrient vessel, we surgically implanted a host arteriovenous (AV) bundle into the medullary canal to promote host vessel neoangiogenesis. Independent variables included patency of the implanted AV bundle, and use of 2 weeks' FK-506 immunosuppression. After 18 weeks, bone blood flow was measured, and neoangiogenic capillary density quantified. Bone blood flow and capillary density were significantly greater in transiently immunosuppressed recipients with a patent AV pedicle. We conclude that neoangiogenesis from implanted host-derived AV-bundles, combined with short-term immunosuppression maintains blood flow in vascularized bone allografts, and offers potential for clinical application.
authors.affiliation: Department of Orthopedic Surgery, Microvascular Research Laboratory, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Pelzer
authors.forename: Mikko
authors.initials: M
authors.lastname: Larsen
authors.forename: Yang-Guk
authors.initials: YG
authors.lastname: Chung
authors.forename: Teruyasu
authors.initials: T
authors.lastname: Ohno
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Platt
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Friedrich
authors.forename: Allen T
authors.initials: AT
authors.lastname: Bishop
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D016025:Bone Transplantation / Q000379:methods*; D005260:Female; D005269:Femur / Q000098:blood supply* / Q000473:pathology / Q000601:surgery*; D007165:Immunosuppression Therapy / Q000379:methods; D018919:Neovascularization, Physiologic; D051381:Rats; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014654:Vascular Patency; D014656:Vascular Surgical Procedures / Q000009:adverse effects / Q000379:methods*; D014945:Wound Healing