Injectable recombinant block polymer gel for sustained delivery of therapeutic protein in post traumatic osteoarthritis

Priya Katyal, Aubryanna Hettinghouse, Michael Meleties, Sadaf Hasan, Changhong Chen, Min Cui, Guodong Sun, Rajiv Menon, Bonnie Lin, Ravinder Regatte, Jin Kim Montclare, Chuan ju Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Protein-based biomaterials offer several advantages over synthetic materials, owing to their unique stimuli-responsive properties, biocompatibility and modular nature. Here, we demonstrate that E5C, a recombinant protein block polymer, consisting of five repeats of elastin like polypeptide (E) and a coiled-coil domain of cartilage oligomeric matrix protein (C), is capable of forming a porous networked gel at physiological temperature, making it an excellent candidate for injectable biomaterials. Combination of E5C with Atsttrin, a chondroprotective engineered derivative of anti-inflammatory growth factor progranulin, provides a unique biochemical and biomechanical environment to protect against post-traumatic osteoarthritis (PTOA) onset and progression. E5C gel was demonstrated to provide prolonged release of Atsttrin and inhibit chondrocyte catabolism while facilitating anabolic signaling in vitro. We also provide in vivo evidence that prophylactic and therapeutic application of Atsttrin-loaded E5C gels protected against PTOA onset and progression in a rabbit anterior cruciate ligament transection model. Collectively, we have developed a unique protein-based gel capable of minimally invasive, sustained delivery of prospective therapeutics, particularly the progranulin-derivative Atsttrin, for therapeutic application in OA.

Original languageEnglish (US)
Article number121370
JournalBiomaterials
Volume281
DOIs
StatePublished - Feb 2022

Keywords

  • Atsttrin
  • Injectable protein engineered gels
  • Post traumatic osteoarthritis
  • Progranulin
  • Rabbit anterior cruciate ligament transection model
  • Recombinant block polymer gels
  • Sustained delivery

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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