title: Accelerated repair of cortical bone defects using a synthetic extracellular matrix to deliver human demineralized bone matrix.
abstract: Injectable hydrogel and porous sponge formulations of Carbylan-GSX, a crosslinked synthetic extracellular matrix (ECM), were used to deliver human demineralized bone matrix (DBM) in a rat femoral defect model. A cortical, full-thickness 5-mm defect was created in two femurs of each rat. Six rats were assigned to each of five experimental groups (thus, 12 defects per group). The defects were either untreated or filled with Carbylan-GSX hydrogel or sponges with or without 20% (w/v) DBM. Radiographs were obtained on day 1 and at weeks 2, 4, 6, and 8 postsurgery of each femur. Animals were sacrificed at week 8 postsurgery and each femur was fixed, embedded, sectioned, and processed for Masson's Trichrome staining. The bone defects were measured from radiographs and the fraction of bone healing was calculated. The average fractions of bone healing for each group were statistically different among all groups, and all treatment groups were significantly better than the control group. The Carbylan-GSX sponge with DBM was superior to the sponge without DBM and to the hydrogel with DBM. Histology showed that defects treated with the Carbylan-GSX sponge plus DBM were completely filled with newly generated bone tissue with a thickness comparable to native bone. Carbylan-GSX sponge was an optimal delivery vehicle for human DBM to accelerate bone healing.
authors.affiliation: Department of Medicinal Chemistry and Center for Therapeutic Biomaterials, The University of Utah, 419 Wakara Way Suite 205, Salt Lake City, Utah, 84108, USA.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Liu
authors.forename: Shama
authors.initials: S
authors.lastname: Ahmad
authors.forename: Xiao Zheng
authors.initials: XZ
authors.lastname: Shu
authors.forename: R Kent
authors.initials: RK
authors.lastname: Sanders
authors.forename: Sally Anne
authors.initials: SA
authors.lastname: Kopesec
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Prestwich
mesh_terms: D000818:Animals; D001857:Bone Matrix; D018786:Bone Substitutes / Q000008:administration & dosage / Q000494:pharmacology*; D005109:Extracellular Matrix; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D005780:Gelatin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D020100:Hydrogels; D008297:Male; D016348:Osseointegration / Q000187:drug effects*; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018786:Bone Substitutes; D020100:Hydrogels; C513409:carbylan-GSX; D005780:Gelatin; D006820:Hyaluronic Acid