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A hyaluronic acid binding peptide-polymer system for treating osteoarthritis.
Faust, Heather J; Sommerfeld, Sven D; Rathod, Sona; Rittenbach, Andrew; Ray Banerjee, Sangeeta; Tsui, Benjamin M W; Pomper, Martin; Amzel, Mario L; Singh, Anirudha; Elisseeff, Jennifer H.
Afiliación
  • Faust HJ; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21287, USA.
  • Sommerfeld SD; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21287, USA.
  • Rathod S; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21287, USA.
  • Rittenbach A; Information Sciences Institute, University of Southern California, Arlington, VA 22203, USA.
  • Ray Banerjee S; Department of Radiology, Johns Hopkins University, Baltimore, MD, 21287, USA.
  • Tsui BMW; Department of Radiology, Johns Hopkins University, Baltimore, MD, 21287, USA.
  • Pomper M; Department of Radiology, Johns Hopkins University, Baltimore, MD, 21287, USA.
  • Amzel ML; Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, MD, 21218, USA.
  • Singh A; 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; Departme
  • Elisseeff JH; Translational Tissue Engineering Center, Wilmer Eye Institute and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21287, USA. Electronic address: jhe@jhu.edu.
Biomaterials ; 183: 93-101, 2018 11.
Article en En | MEDLINE | ID: mdl-30149233
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligopéptidos / Osteoartritis / Polietilenglicoles / Portadores de Fármacos / Ácido Hialurónico Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biomaterials Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oligopéptidos / Osteoartritis / Polietilenglicoles / Portadores de Fármacos / Ácido Hialurónico Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Biomaterials Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos