title: Multi-layered collagen-based scaffolds for osteochondral defect repair in rabbits.
abstract: BACKGROUND
  Identification of a suitable treatment for osteochondral repair presents a major challenge due to existing limitations and an urgent clinical need remains for an off-the-shelf, low cost, one-step approach. A biomimetic approach, where the biomaterial itself encourages cellular infiltration from the underlying bone marrow and provides physical and chemical cues to direct these cells to regenerate the damaged tissue, provides a potential solution. To meet this need, a multi-layer collagen-based osteochondral defect repair scaffold has been developed in our group.
  
  
  OBJECTIVE
  The objective of this study was to assess the in vivo response to this scaffold and determine its ability to direct regenerative responses in each layer in order to repair osteochondral tissue in a critical-sized defect in a rabbit knee.
  
  
  METHODS
  Multi-layer scaffolds, consisting of a bone layer composed of type I collagen (bovine source) and hydroxyapatite (HA), an intermediate layer composed of type I and type II collagen and HA; and a superficial layer composed of type I and type II collagen (porcine source) and hyaluronic acid (HyA), were implanted into critical size (3 × 5 mm) osteochondral defects created in the medial femoral condyle of the knee joint of New Zealand white rabbits and compared to an empty control group. Repair was assessed macroscopically, histologically and using micro-CT analysis at 12 weeks post implantation.
  
  
  RESULTS
  Analysis of repair tissue demonstrated an enhanced macroscopic appearance in the multi-layer scaffold group compared to the empty group. In addition, diffuse host cellular infiltration in the scaffold group resulted in tissue regeneration with a zonal organisation, with repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark.
  
  
  CONCLUSIONS
  These results demonstrate the potential of this biomimetic multi-layered scaffold to support and guide the host reparative response in the treatment of osteochondral defects.
  
  
  CONCLUSIONS
  Osteochondral defects, involving cartilage and the underlying subchondral bone, frequently occur in young active patients due to disease or injury. While some treatment options are available, success is limited and patients often eventually require joint replacement. To address this clinical need, a multi-layer collagen-based osteochondral defect repair scaffold designed to direct host-stem cell mediated tissue formation within each region, has been developed in our group. The present study investigates the in vivo response to this scaffold in a critical-sized defect in a rabbit knee. Results shows the scaffolds ability to guide the host reparative response leading to tissue regeneration with a zonal organisation, repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark.
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland.
authors.forename: Tanya J
authors.initials: TJ
authors.lastname: Levingstone
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland.
authors.forename: Emmet
authors.initials: E
authors.lastname: Thompson
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland.
authors.forename: Amos
authors.initials: A
authors.lastname: Matsiko
authors.affiliation: Department of Orthopaedic Surgery, AZ Sint-Lucas Hospital, Ghent, Belgium.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schepens
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland; SurgaColl Technologies Ltd., Invent Centre, Dublin City University, Dublin, Ireland.
authors.forename: John P
authors.initials: JP
authors.lastname: Gleeson
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland. Electronic address: fjobrien@rcsi.ie.
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D002417:Cattle; D003094:Collagen / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology* / Q000601:surgery; D007150:Immunohistochemistry; D011817:Rabbits; D034421:Sus scrofa; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D003094:Collagen
keywords: Cartilage; Collagen; In vivo; Osteochondral; Tissue engineering