title: Blocking collagen fibril formation in injured knees reduces flexion contracture in a rabbit model.
abstract: Post-traumatic joint contracture is a frequent orthopaedic complication that limits the movement of injured joints, thereby severely impairing affected patients. Non-surgical and surgical treatments for joint contracture often fail to improve the range of motion. In this study, we tested a hypothesis that limiting the formation of collagen-rich tissue in the capsules of injured joints would reduce the consequences of the fibrotic response and improve joint mobility. We targeted the formation of collagen fibrils, the main component of fibrotic deposits formed within the tissues of injured joints, by employing a relevant rabbit model to test the utility of a custom-engineered antibody. The antibody was delivered directly to the cavities of injured knees in order to block the formation of collagen fibrils produced in response to injury. In comparison to the non-treated control, mechanical tests of the antibody-treated knees demonstrated a significant reduction of flexion contracture. Detailed microscopic and biochemical studies verified that this reduction resulted from the antibody-mediated blocking of the assembly of collagen fibrils. These findings indicate that extracellular processes associated with excessive formation of fibrotic tissue represent a valid target for limiting post-traumatic joint stiffness. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1038-1046, 2017.
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Steplewski
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Fertala
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107.
authors.forename: Pedro K
authors.initials: PK
authors.lastname: Beredjiklian
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Abboud
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107.
authors.forename: Mark L Y
authors.initials: MLY
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107.
authors.forename: Surena
authors.initials: S
authors.lastname: Namdari
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barlow
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107.
authors.forename: Michael
authors.initials: M
authors.lastname: Rivlin
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.|Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19107.
authors.forename: William V
authors.initials: WV
authors.lastname: Arnold
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.
authors.forename: James
authors.initials: J
authors.lastname: Kostas
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Curtis Building, 1015 Walnut Street, Philadelphia, Pennsylvania 19107.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Fertala
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D024042:Collagen Type I / Q000037:antagonists & inhibitors; D024061:Collagen Type III / Q000378:metabolism; D003286:Contracture / Q000209:etiology / Q000517:prevention & control*; D005240:Feasibility Studies; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism*; D007718:Knee Injuries / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000906:Antibodies; D024042:Collagen Type I; D024061:Collagen Type III; D024022:Fibrillar Collagens; D011994:Recombinant Proteins
keywords: antibody; arthrofibrosis; collagen fibrils; joint contracture; posterior capsule collagen