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Engineering endostatin-expressing cartilaginous constructs using injectable biopolymer hydrogels.

Lily Jeng1, Bjorn R Olsen, Myron Spector

  • 1Tissue Engineering, VA Boston Healthcare System, Boston, MA 02130, USA.

Acta Biomaterialia
|February 29, 2012
PubMed
Summary

Injectable hydrogels with mesenchymal stem cells (MSCs) can deliver endostatin for cartilage repair. While endostatin release was high, engineered constructs showed potential for articular cartilage regeneration.

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Tissue Engineering

Background:

  • Articular cartilage repair presents challenges, with anti-angiogenic agents like endostatin showing therapeutic potential.
  • Developing injectable, in vivo cross-linking scaffolds for cell delivery and protein expression is crucial for cartilage regeneration.

Purpose of the Study:

  • To engineer an injectable, mesenchymal stem cell (MSC)-laden collagen hydrogel for in vivo endostatin overexpression and investigate endostatin retention methods.
  • To evaluate the efficacy of different cross-linking agents and binding molecules for enhancing endostatin retention within the scaffold.

Main Methods:

  • Development of an injectable collagen-based hydrogel incorporating MSCs.
  • Nonviral transfection of MSCs for endostatin overexpression.

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  • Evaluation of cross-linking agents (genipin, transglutaminase-2, microbial transglutaminase) and binding molecules (heparin, heparan sulfate, chondroitin sulfate) for endostatin retention.
  • Engineering of cartilaginous constructs overexpressing endostatin for 3 weeks.

    • Main Results:

    • Successfully engineered endostatin-overexpressing cartilaginous constructs.
    • Significant endostatin release into surrounding media, indicating limited retention within constructs.
    • Detection of laminin and type IV collagen within engineered constructs, mirroring native cartilage basement membranes.

    Conclusions:

    • Endostatin-producing cartilaginous constructs can be formulated using nonvirally transfected MSCs in covalently cross-linked collagen gels.
    • These constructs show promise for cartilage repair, warranting further investigation.
    • The presence of laminin and type IV collagen in engineered constructs offers novel insights into chondrogenesis and cartilage physiology.