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Nanoparticle-Mediated TGF-β Release from Microribbon-Based Hydrogels Accelerates Stem Cell-Based Cartilage Formation

Danial Barati1, Courtney Gegg2, Fan Yang3

  • 1Department of Orthopedic Surgery, Stanford University Schools of Engineering and Medicine, 300 Pasteur Drive, Edwards R105, Stanford, CA, 94305, USA.

Annals of Biomedical Engineering
|May 8, 2020
PubMed
Summary

This study developed polydopamine-coated mesoporous silica nanoparticles (MSNs) for controlled release of transforming growth factor-β3 (TGF-β3). These nanoparticles enhance stem cell-based cartilage regeneration in vitro and in vivo within macroporous hydrogel scaffolds.

Keywords:
CartilageControlled releaseMesenchymal stem cellsMesoporous silica nanoparticleTransforming growth factor beta3

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Area of Science:

  • Biomaterials Science
  • Tissue Engineering
  • Nanotechnology

Background:

  • Conventional hydrogels show limitations in supporting mesenchymal stem cell (MSC) chondrogenesis due to physical constraints and degradation.
  • Macroporous gelatin microribbon (μRB) hydrogels accelerate MSC-based cartilage formation but require improved drug delivery for in vivo translation.
  • Controlled delivery of growth factors like transforming growth factor-β3 (TGF-β3) is crucial for effective cartilage regeneration.

Purpose of the Study:

  • To develop a customizable drug delivery system using polydopamine-coated mesoporous silica nanoparticles (MSNs) for incorporation into μRB hydrogel scaffolds.
  • To investigate the effect of polydopamine coating concentration on TGF-β3 release kinetics from MSNs.
  • To evaluate the efficacy of MSN-mediated TGF-β3 delivery in enhancing MSC-based cartilage formation in vitro and in vivo.

Main Methods:

  • Synthesis and characterization of polydopamine-coated MSNs loaded with TGF-β3.
  • Incorporation of coated MSNs into macroporous μRB hydrogel scaffolds.
  • In vitro assessment of TGF-β3 release, MSC proliferation, and chondrogenesis using biochemical assays, mechanical testing, and histology.
  • In vivo evaluation in a mouse subcutaneous model to assess cartilage formation and tissue integration.

Main Results:

  • Polydopamine coating on MSNs enabled tunable release of TGF-β3, with increased coating slowing down release.
  • MSN-mediated TGF-β3 delivery significantly enhanced MSC-based cartilage regeneration in vitro, achieving levels comparable to free TGF-β3.
  • In vivo studies demonstrated sustained cartilage formation with MSN-mediated TGF-β3 release, preventing matrix loss and endochondral ossification.

Conclusions:

  • Polydopamine-coated MSNs provide a modular and customizable drug delivery system for μRB hydrogel scaffolds.
  • This system effectively enhances MSC-based cartilage regeneration both in vitro and in vivo.
  • The developed platform holds potential for regenerating other tissue types by enabling controlled delivery of multiple therapeutic agents.