An alginate-poly(acrylamide) hydrogel with TGF-β3 loaded nanoparticles for cartilage repair: Biodegradability, biocompatibility and protein adsorption

Int J Biol Macromol. 2021 Mar 1:172:381-393. doi: 10.1016/j.ijbiomac.2021.01.069. Epub 2021 Jan 18.

Abstract

Current implantable materials are limited in terms of function as native tissue, and there is still no effective clinical treatment to restore articular impairments. Hereby, a functionalized polyacrylamide (PAAm)-alginate (Alg) Double Network (DN) hydrogel acting as an articular-like tissue is developed. These hydrogels sustain their mechanical stability under different temperature (+4 °C, 25 °C, 40 °C) and humidity conditions (60% and 75%) over 3 months. As for the functionalization, transforming growth factor beta-3 (TGF-β3) encapsulated (NPTGF-β3) and empty poly(lactide-co-glycolide) (PLGA) nanoparticles (PLGA NPs) are synthesized by using microfluidic platform, wherein the mean particle sizes are determined as 81.44 ± 9.2 nm and 126 ± 4.52 nm with very low polydispersity indexes (PDI) of 0.194 and 0.137, respectively. Functionalization process of PAAm-Alg hydrogels with ester-end PLGA NPs is confirmed by FTIR analysis, and higher viscoelasticity is obtained for functionalized hydrogels. Moreover, cartilage regeneration capability of these hydrogels is evaluated with in vitro and in vivo experiments. Compared with the PAAm-Alg hydrogels, functionalized formulations exhibit a better cell viability. Histological staining, and score distribution confirmed that proposed hydrogels significantly enhance regeneration of cartilage in rats due to stable hydrogel matrix and controlled release of TGF-β3. These findings demonstrated that PAAm-Alg hydrogels showed potential for cartilage repair and clinical application.

Keywords: Alginate; Articular cartilage; Double network hydrogels; Growth factor; Nanoparticles.

MeSH terms

  • Absorbable Implants
  • Acrylic Resins / chemistry*
  • Alginates / chemistry*
  • Animals
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / pharmacology
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / growth & development
  • Cartilage, Articular / injuries
  • Cell Survival / drug effects
  • Chondrocytes / cytology
  • Chondrocytes / drug effects
  • Chondrocytes / physiology
  • Drug Compounding / methods
  • Hindlimb / drug effects
  • Hydrogels / chemistry*
  • Male
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta3 / chemistry
  • Transforming Growth Factor beta3 / metabolism
  • Transforming Growth Factor beta3 / pharmacokinetics*
  • Treatment Outcome

Substances

  • Acrylic Resins
  • Alginates
  • Biocompatible Materials
  • Hydrogels
  • Tgfb3 protein, rat
  • Transforming Growth Factor beta3
  • polyacrylamide