Customized biomaterials to augment chondrocyte gene therapy

Izath Nizeet Aguilar, Stephen Trippel, Shuiliang Shi, Lawrence J. Bonassar

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

A persistent challenge in enhancing gene therapy is the transient availability of the target gene product. This is particularly true in tissue engineering applications. The transient exposure of cells to the product could be insufficient to promote tissue regeneration. Here we report the development of a new material engineered to have a high affinity for a therapeutic gene product. We focus on insulin-like growth factor-I (IGF-I) for its highly anabolic effects on many tissues such as spinal cord, heart, brain and cartilage. One of the ways that tissues store IGF-I is through a group of insulin like growth factor binding proteins (IGFBPs), such as IGFBP-5. We grafted the IGF-I binding peptide sequence from IGFBP-5 onto alginate in order to retain the endogenous IGF-I produced by transfected chondrocytes. This novel material bound IGF-I and released the growth factor for at least 30. days in culture. We found that this binding enhanced the biosynthesis of transfected cells up to 19-fold. These data demonstrate the coordinated engineering of cell behavior and material chemistry to greatly enhance extracellular matrix synthesis and tissue assembly, and can serve as a template for the enhanced performance of other therapeutic proteins. Statement of Significance: The present manuscript focuses on the enhancement of chondrocyte gene therapy through the modification of scaffold materials to enhance the retention of targeted gene products. This study combined tissue engineering and gene therapy, where customized biomaterials augmented the action of IGF-I by enhancing the retention of protein produced by transfection of the IGF-I gene. This approach enabled tuning of binding of IGF-I to alginate, which increased GAG and HYPRO production by transfected chondrocytes. To our knowledge, peptide-based modification of materials to augment growth factor-targeted gene therapy has not been reported previously.

Original languageEnglish (US)
JournalActa Biomaterialia
DOIs
StateAccepted/In press - Oct 5 2016

Fingerprint

Gene therapy
Biocompatible Materials
Chondrocytes
Insulin-Like Growth Factor I
Biomaterials
Insulin
Genetic Therapy
Genes
Insulin-Like Growth Factor Binding Protein 5
Tissue Engineering
Tissue
Tissue engineering
Intercellular Signaling Peptides and Proteins
Alginate
Cell Engineering
Anabolic Agents
Insulin-Like Growth Factor Binding Proteins
Tissue regeneration
Peptides
Manuscripts

Keywords

  • Binding peptide
  • Growth factor
  • IGF-I
  • Osteoarthritis

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering
  • Molecular Biology

Cite this

Aguilar, I. N., Trippel, S., Shi, S., & Bonassar, L. J. (Accepted/In press). Customized biomaterials to augment chondrocyte gene therapy. Acta Biomaterialia. https://doi.org/10.1016/j.actbio.2017.02.008

Customized biomaterials to augment chondrocyte gene therapy. / Aguilar, Izath Nizeet; Trippel, Stephen; Shi, Shuiliang; Bonassar, Lawrence J.

In: Acta Biomaterialia, 05.10.2016.

Research output: Contribution to journalArticle

Aguilar, Izath Nizeet ; Trippel, Stephen ; Shi, Shuiliang ; Bonassar, Lawrence J. / Customized biomaterials to augment chondrocyte gene therapy. In: Acta Biomaterialia. 2016.
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