Inspired by lubricin: a tailored cartilage-armor with durable lubricity and autophagy-activated antioxidation for targeted therapy of osteoarthritis

Mater Horiz. 2024 Oct 28;11(21):5352-5365. doi: 10.1039/d4mh00812j.

Abstract

Osteoarthritis (OA), which disables articular cartilage, affects millions of people. The self-healing capacity is inhibited by internal oxidative stress and external lubrication deficiency and enzymatic degradation. To overcome these challenges, a tailored cartilage-armor is designed to ameliorate the inflamed cartilage, which is implemented by a novel collagen type II (Col II)-binding peptide conjugated zwitterionic polymer (PSB-b-PColBP, PSP). By mimicking natural lubricin, PSP specifically targets the cartilage surface and forms an in situ hydration armor. This engineered cartilage-armor can prevent enzymatic cartilage degradation (nearly 100% resistance to catabolic enzymes) and provide durable lubrication properties (COF < 0.013 for 500 cycles). An autophagy-activation process, absent in previous biomimetic lubricants, enhances the enzymatic activity of the tailored cartilage-armor, offering effective anti-oxidant properties to suppress oxidative stress. By inhibiting the PI3K-Akt/NF-κB signaling pathway, chondrocytes protected by the tailored armor can secrete a cartilage matrix even in inflammatory microenvironments. In OA rat models, osteophyte formation and the inflammatory response have been inhibited by the cartilage-armor, demonstrating a therapeutic effect comparable to most drug-loaded systems. This study underscores the potential of tailoring cartilage-armor with the cartilage targeting and autophagy-activating properties in integrating offensive-defensive mechanisms for cartilage remodeling. This represents an alternative strategy for clinical OA therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants* / pharmacology
  • Antioxidants* / therapeutic use
  • Autophagy* / drug effects
  • Autophagy* / physiology
  • Cartilage, Articular* / drug effects
  • Cartilage, Articular* / metabolism
  • Cartilage, Articular* / pathology
  • Chondrocytes* / drug effects
  • Chondrocytes* / metabolism
  • Collagen Type II / metabolism
  • Disease Models, Animal
  • Glycoproteins* / metabolism
  • Glycoproteins* / pharmacology
  • Glycoproteins* / therapeutic use
  • Humans
  • Lubricants / pharmacology
  • Lubricants / therapeutic use
  • Lubrication
  • Male
  • Osteoarthritis* / drug therapy
  • Osteoarthritis* / pathology
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects

Substances

  • lubricin
  • Glycoproteins
  • Antioxidants
  • Collagen Type II
  • Lubricants