title: Surgical membranes as directional delivery devices to generate tissue: testing in an ovine critical sized defect model.
abstract: OBJECTIVE
  Pluripotent cells residing in the periosteum, a bi-layered membrane enveloping all bones, exhibit a remarkable regenerative capacity to fill in critical sized defects of the ovine femur within two weeks of treatment. Harnessing the regenerative power of the periosteum appears to be limited only by the amount of healthy periosteum available. Here we use a substitute periosteum, a delivery device cum implant, to test the hypothesis that directional delivery of endogenous periosteal factors enhances bone defect healing.
  
  
  METHODS
  Newly adapted surgical protocols were used to create critical sized, middiaphyseal femur defects in four groups of five skeletally mature Swiss alpine sheep. Each group was treated using a periosteum substitute for the controlled addition of periosteal factors including the presence of collagen in the periosteum (Group 1), periosteum derived cells (Group 2), and autogenic periosteal strips (Group 3). Control group animals were treated with an isotropic elastomer membrane alone. We hypothesized that periosteal substitute membranes incorporating the most periosteal factors would show superior defect infilling compared to substitute membranes integrating fewer factors (i.e. Group 3>Group 2>Group 1>Control).
  
  
  RESULTS
  Based on micro-computed tomography data, bone defects enveloped by substitute periosteum enabling directional delivery of periosteal factors exhibit superior bony bridging compared to those sheathed with isotropic membrane controls (Group 3>Group 2>Group 1, Control). Quantitative histological analysis shows significantly increased de novo tissue generation with delivery of periosteal factors, compared to the substitute periosteum containing a collagen membrane alone (Group 1) as well as compared to the isotropic control membrane. Greatest tissue generation and maximal defect bridging was observed when autologous periosteal transplant strips were included in the periosteum substitute.
  
  
  CONCLUSIONS
  Periosteum-derived cells as well as other factors intrinsic to periosteum play a key role for infilling of critical sized defects.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States of America. knothetate@case.edu
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Knothe Tate
authors.forename: Hana
authors.initials: H
authors.lastname: Chang
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Moore
authors.forename: Ulf R
authors.initials: UR
authors.lastname: Knothe
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery*; D007432:Intraoperative Period; D010521:Periosteum / Q000473:pathology; D012756:Sheep; D013194:Staining and Labeling; D023822:Tissue Engineering / Q000379:methods*; D055114:X-Ray Microtomography