title: Repair of a critical size defect in the rat mandible using allogenic type I collagen.
abstract: Mandibular fractures, resulting from either trauma or reconstructive surgery, can be challenging craniofacial problems. The morbidity of failed fracture healing is significant and may require bone grafting. Donor site morbidity and finite amounts of autogenous bone are major drawbacks of autogenous bone grafting. Similarly, the use of allografts and xenografts may be associated with an increased risk of rejection, infection, and nonunion. To circumvent the limitations of bone grafting, research efforts have focused on formulating a suitable bone substitute. The purpose of our study was to evaluate the efficacy of type I collagen implants in repairing critical sized mandibular defects in rats. Twelve male Sprague-Dawley rats (200-300g) were divided equally into control and experimental groups. Full thickness, round, four millimeter in diameter defects were created in the ramus of the right mandible of all rats using an electrical burr at low speed. The defects were irrigated of all bone chips, and either filled with a precisely fitted disk of allogenic collagen type I gel (experimental animals) or left empty (control animals). Animals were killed 6 weeks after surgery and healing of the bone defects was assessed in a blinded fashion using radiologic and histologic analysis. Radiologic analysis of the control group revealed a clear circular right mandibular defect in all animals, whereas the collagen disk implant group revealed an indistinct to nonexistent right mandibular defect in all animals. Densitometric analysis revealed a significant difference between these groups (* P = 0.01). Similarly, gross analysis of control mandibles revealed a 4mm round, soft-tissue filled defect, while implanted defects demonstrated gross bone spanning the defect. Finally, histologic analysis of all control mandibles revealed clearly demarcated bony edges at the defect border with connective tissue spanning the defect. In contrast, histological analysis of all implanted mandibles revealed indistinct bony edges at the defect border with a thin layer of osteoblasts and viable bone spanning the defects. We have demonstrated the ability of type I collagen to promote healing of a membranous bony defect that would not otherwise heal at 6 weeks. The suitability of type I collagen as a carrier matrix provides ample opportunity for tissue-engineered approaches to further facilitate bony defect healing. Promoting bone formation through tissue engineering matrices offers great promise for skeletal healing and reconstruction.
authors.affiliation: Department of Surgery, University of Connecticut, Farmington, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Saadeh
authors.forename: R K
authors.initials: RK
authors.lastname: Khosla
authors.forename: B J
authors.initials: BJ
authors.lastname: Mehrara
authors.forename: D S
authors.initials: DS
authors.lastname: Steinbrech
authors.forename: S A
authors.initials: SA
authors.lastname: McCormick
authors.forename: D P
authors.initials: DP
authors.lastname: DeVore
authors.forename: M T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D015502:Absorptiometry, Photon; D000704:Analysis of Variance; D000818:Animals; D018786:Bone Substitutes / Q000627:therapeutic use*; D024042:Collagen Type I / Q000627:therapeutic use*; D004396:Coloring Agents; D003238:Connective Tissue / Q000473:pathology; D004195:Disease Models, Animal; D004337:Drug Carriers; D005456:Fluorescent Dyes; D005782:Gels; D008297:Male; D008336:Mandibular Diseases / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D010006:Osteoblasts / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology; D010027:Osteotomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D016037:Single-Blind Method; D013223:Statistics as Topic; D023822:Tissue Engineering; D016896:Treatment Outcome; D014945:Wound Healing
chemical_list: D018786:Bone Substitutes; D024042:Collagen Type I; D004396:Coloring Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D005782:Gels