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A Baicalin-Based Functional Polymer in Dynamic Reversible Networks Alleviates Osteoarthritis by Cellular

Yili Yang1,2, Qinxiao Hu1, Qingfeng Shao1

  • 1Department of Bone and Joint Surgery, the First Affiliated Hospital of Jinan University, Key Laboratory of Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, Guangdong, 510630, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|January 22, 2025
PubMed
Summary

This study introduces a novel flavonoid-based hydrogel for osteoarthritis treatment. The injectable hydrogel effectively reduces inflammation and cartilage degradation by regulating cell metabolism and targeting key signaling pathways.

Keywords:
Bai‐based polymerSchiff‐base hydrogelanti‐inflammationglycolysisosteoarthritis

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Area of Science:

  • Biomaterials Science
  • Rheumatology
  • Nanotechnology

Background:

  • Osteoarthritis (OA) is a degenerative joint disease affecting cartilage and bone, with current treatments offering limited resolution.
  • Synovial inflammation and altered cellular metabolism are key pathological features of OA.
  • There is a need for advanced therapeutic strategies to address the multi-faceted nature of OA.

Purpose of the Study:

  • To develop and evaluate a novel functional hydrogel incorporating baicalin (Bai) for osteoarthritis treatment.
  • To investigate the hydrogel's mechanism of action on fibroblast-like synoviocytes (FLSs) and inflammatory pathways.
  • To assess the therapeutic efficacy of the hydrogel in reducing OA-related symptoms and pathology.

Main Methods:

  • Synthesis of a baicalin-based polymer (Pm) via reversible addition-fragmentation chain transfer (RAFT) polymerization.
  • Incorporation of Pm into Schiff-base hydrogels with enhanced mechanical and self-healing properties.
  • In vitro assessment of hydrogel uptake by FLSs, regulation of glycolysis, and inflammatory factor secretion.
  • In vivo evaluation of the hydrogel's lubricity, nutrient delivery, cartilage protection, and pain alleviation in an OA model.

Main Results:

  • The developed hydrogel demonstrated excellent mechanical properties and self-healing capabilities.
  • The hydrogel formulation suppressed FLS glycolysis and reduced pro-inflammatory cytokine secretion (IL-1β, IL-6, IL-8) by inhibiting YAP1.
  • The functional hydrogel (AG-Pm)-OC prolonged joint retention of baicalin, reduced cartilage degradation, and alleviated joint pain.
  • The treatment effectively inhibited macrophage recruitment and polarization, contributing to reduced synovial inflammation.

Conclusions:

  • The baicalin-based injectable hydrogel represents a promising therapeutic strategy for osteoarthritis.
  • Targeting cellular metabolism and inflammatory signaling via YAP1 inhibition is a viable approach for OA treatment.
  • The hydrogel's properties enhance drug delivery and retention, leading to improved biocompatibility and efficacy against OA.