title: Templated repair of long bone defects in rats with bioactive spiral-wrapped electrospun amphiphilic polymer/hydroxyapatite scaffolds.
abstract: Effective repair of critical-size long bone defects presents a significant clinical challenge. Electrospun scaffolds can be exploited to deliver protein therapeutics and progenitor cells, but their standalone application for long bone repair has not been explored. We have previously shown that electrospun composites of amphiphilic poly(d,l-lactic acid)-co-poly(ethylene glycol)-co-poly(d,l-lactic acid) (PELA) and hydroxyapatite (HA) guide the osteogenic differentiation of bone marrow stromal cells (MSCs), making these scaffolds uniquely suited for evaluating cell-based bone regeneration approaches. Here we examine whether the in vitro bioactivity of these electrospun scaffolds can be exploited for long bone defect repair, either through the participation of exogenous MSCs or through the activation of endogenous cells by a low dose of recombinant human bone morphogenetic protein-2 (rhBMP-2). In critical-size rat femoral segmental defects, spiral-wrapped electrospun HA-PELA with preseeded MSCs resulted in laminated endochondral ossification templated by the scaffold across the longitudinal span of the defect. Using GFP labeling, we confirmed that the exogenous MSCs adhered to HA-PELA survived at least 7 days postimplantation, suggesting direct participation of these exogenous cells in templated bone formation. When loaded with 500 ng of rhBMP-2, HA-PELA spirals led to more robust but less clearly templated bone formation than MSC-bearing scaffolds. Both treatment groups resulted in new bone bridging over the majority of the defect by 12 weeks. This study is the first demonstration of a standalone bioactive electrospun scaffold for templated bone formation in critical-size long bone defects.
authors.affiliation: Department of Orthopedics and Physical Rehabilitation and ‡Department of Cell and Developmental Biology, University of Massachusetts Medical School , 55 Lake Avenue North, Worcester, Massachusetts 01655, United States.
authors.forename: Artem B
authors.initials: AB
authors.lastname: Kutikov
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Skelly
authors.forename: David C
authors.initials: DC
authors.lastname: Ayers
authors.forename: Jie
authors.initials: J
authors.lastname: Song
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology; D001861:Bone Regeneration; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017886:Durapatite / Q000737:chemistry* / Q000494:pharmacology; D005264:Femoral Fractures / Q000628:therapy; D007773:Lactates / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D007773:Lactates; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C058523:polyethylene oxide-polylactic acid block copolymer; D011092:Polyethylene Glycols; D017886:Durapatite
keywords: BMP (bone morphogenetic protein); amphiphilic polymer; bone marrow derived stromal cells; bone tissue engineering; electrospinning; hydroxyapatite