A hyaluronic acid binding peptide-polymer system for treating osteoarthritis

Heather J Faust; Sven D Sommerfeld; Sona Rathod; Andrew Rittenbach; Sangeeta Ray Banerjee; Benjamin M W Tsui; Martin Pomper; Mario L Amzel; Anirudha Singh; Jennifer H Elisseeff

doi:10.1016/j.biomaterials.2018.08.045

A hyaluronic acid binding peptide-polymer system for treating osteoarthritis

Biomaterials. 2018 Nov:183:93-101. doi: 10.1016/j.biomaterials.2018.08.045. Epub 2018 Aug 21.

Affiliations

¹ Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21287, USA.
² Information Sciences Institute, University of Southern California, Arlington, VA 22203, USA.
³ Department of Radiology, Johns Hopkins University, Baltimore, MD, 21287, USA.
⁴ Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, MD, 21218, USA.
⁵ Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21287, USA; Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
⁶ Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21287, USA. Electronic address: jhe@jhu.edu.

PMID: 30149233
DOI: 10.1016/j.biomaterials.2018.08.045

Abstract

Hyaluronic acid (HA) is found naturally in synovial fluid and is utilized therapeutically to treat osteoarthritis (OA). Here, we employed a peptide-polymer cartilage coating platform to localize HA to the cartilage surface for the purpose of treating post traumatic osteoarthritis. The objective of this study was to increase efficacy of the peptide-polymer platform in reducing OA progression in a mouse model of post-traumatic OA without exogenous HA supplementation. The peptide-polymer is composed of an HA-binding peptide (HABP) conjugated to a heterobifunctional poly (ethylene glycol) (PEG) chain and a collagen binding peptide (COLBP). We created a library of different peptide-polymers and characterized their HA binding properties in vitro using quartz crystal microbalance (QCM-D) and isothermal calorimetry (ITC). The peptide polymers were further tested in vivo in an anterior cruciate ligament transection (ACLT) murine model of post traumatic OA. The peptide-polymer with the highest affinity to HA as tested by QCM-D (∼4-fold greater binding compared to other peptides tested) and by ITC (∼3.8-fold) was HABP2-8-arm PEG-COLBP. Biotin tagging demonstrated that HABP2-8-arm PEG-COLBP localizes to both cartilage defects and synovium. In vivo, HABP2-8-arm PEG-COLBP treatment and the clinical HA comparator Orthovisc lowered levels of inflammatory genes including IL-6, IL-1B, and MMP13 compared to saline treated animals and increased aggrecan expression in young mice. HABP2-8-arm PEG-COLBP and Orthovisc also reduced pain as measured by incapacitance and hotplate testing. Cartilage degeneration as measured by OARSI scoring was also reduced by HABP2-8-arm PEG-COLBP and Orthovisc. In aged mice, HABP2-8-arm PEG-COLBP therapeutic efficacy was similar to its efficacy in young mice, but Orthovisc was less efficacious and did not significantly improve OARSI scoring. These results demonstrate that HABP2-8-arm PEG-COLBP is effective at reducing PTOA progression.

Keywords: Anterior cruciate ligament; Cartilage; Hyaluronic acid; Hyaluronic acid binding peptide; Osteoarthritis; Peptide-polymer.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Anterior Cruciate Ligament / drug effects
Anterior Cruciate Ligament / pathology
Cartilage, Articular / drug effects
Cartilage, Articular / metabolism
Cartilage, Articular / pathology
Collagen / chemistry
Drug Carriers / chemistry*
Hyaluronic Acid / analogs & derivatives
Hyaluronic Acid / chemistry
Hyaluronic Acid / metabolism
Hyaluronic Acid / pharmacology*
Interleukins / metabolism
Matrix Metalloproteinase 13 / metabolism
Mice
Nanoparticles / chemistry
Oligopeptides / chemistry*
Osteoarthritis / drug therapy*
Osteoarthritis / pathology
Polyethylene Glycols / chemistry*
Small Molecule Libraries
Synovial Membrane / metabolism

Substances

Drug Carriers
Interleukins
Oligopeptides
Small Molecule Libraries
orthovisc
Polyethylene Glycols
Hyaluronic Acid
Collagen
Matrix Metalloproteinase 13