title: Cartilage repair and subchondral bone remodeling in response to focal lesions in a mini-pig model: implications for tissue engineering.
abstract: OBJECTIVE
  Preclinical large animal models are essential for evaluating new tissue engineering (TE) technologies and refining surgical approaches for cartilage repair. Some preclinical animal studies, including the commonly used minipig model, have noted marked remodeling of the subchondral bone. However, the mechanisms underlying this response have not been well characterized. Thus, our objective was to compare in-vivo outcomes of chondral defects with varied injury depths and treatments.
  
  
  METHODS
  Trochlear chondral defects were created in 11 Yucatan minipigs (6 months old). Groups included an untreated partial-thickness defect (PTD), an untreated full-thickness defect (FTD), and FTDs treated with microfracture, autologous cartilage transfer (FTD-ACT), or an acellular hyaluronic acid hydrogel. Six weeks after surgery, micro-computed tomography (μCT) was used to quantitatively assess defect fill and subchondral bone remodeling. The quality of cartilage repair was assessed using the ICRS-II histological scoring system and immunohistochemistry for type II collagen. A finite element model (FEM) was developed to assess load transmission.
  
  
  RESULTS
  Using μCT, substantial bone remodeling was observed for all FTDs, but not for the PTD group. The best overall histological scores and greatest type II collagen staining was found for the FTD-ACT and PTD groups. The FEM confirmed that only the FTD-ACT group could initially restore appropriate transfer of compressive loads to the underlying bone.
  
  
  CONCLUSIONS
  The bony remodeling observed in this model system appears to be a biological phenomena and not a result of altered mechanical loading, with the depth of the focal chondral defect (partial vs. full thickness) dictating the bony remodeling response. The type of cartilage injury should be carefully controlled in studies utilizing this model to evaluate TE approaches for cartilage repair.
authors.affiliation: 1 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Fisher
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Belkin
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Milby
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Henning
authors.forename: Marc
authors.initials: M
authors.lastname: Bostrom
authors.forename: Minwook
authors.initials: M
authors.lastname: Kim
authors.forename: Christian
authors.initials: C
authors.lastname: Pfeifer
authors.forename: Gregory
authors.initials: G
authors.lastname: Meloni
authors.forename: George R
authors.initials: GR
authors.lastname: Dodge
authors.forename: Jason A
authors.initials: JA
authors.lastname: Burdick
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Schaer
authors.forename: David R
authors.initials: DR
authors.lastname: Steinberg
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mauck
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D002356:Cartilage / Q000637:transplantation*; D017102:Fracture Healing / Q000502:physiology*; D050724:Fractures, Cartilage / Q000000981:diagnostic imaging / Q000628:therapy*; D011859:Radiography; D013552:Swine; D013556:Swine, Miniature; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D016896:Treatment Outcome