CUSTOMIZED BIOMATERIALS TO AUGMENT CHONDROCYTE GENE THERAPY

Acta Biomater, 2017 · DOI: 10.1016/j.actbio.2017.02.008 · Published: April 15, 2017

Simple Explanation

The study focuses on engineering a material with high affinity for a therapeutic gene product, specifically insulin-like growth factor–I (IGF-I), to enhance gene therapy. The researchers grafted an IGF-I binding peptide sequence from IGFBP-5 onto alginate to retain the IGF-I produced by transfected chondrocytes. The novel material bound IGF-I and released it for at least 30 days, enhancing the biosynthesis of transfected cells significantly.

Study Duration

30 days

Participants

Articular cartilage from stifle (knee) condyles of 1–3 day old bovids (Bos taurus)

Evidence Level

Not specified

Key Findings

1
A novel material was created by grafting the IGF-I binding peptide sequence from IGFBP-5 onto alginate.
2
This material bound IGF-I and released the growth factor for at least 30 days in culture.
3
The binding enhanced the biosynthesis of transfected cells up to 19-fold.

Research Summary

This study demonstrates the coordinated engineering of cell behavior and material chemistry to greatly enhance extracellular matrix synthesis and tissue assembly. The new material with high affinity for IGF-I by grafting a binding peptide sequence from IGFBP-5 onto alginate, greatly extends the availability of the growth factor during chondrocyte culture. The modified alginate with the peptide KPLHALL from the binding pocket of IGFBP-5 enhanced binding affinity more than 10-fold, extended IGF-I availability over 30 days and increased GAG and HYPRO synthesis 7 and 20 fold respectively.

Practical Implications

Enhanced Cartilage Repair

The modified alginate shows great promise to further improve chondrocyte matrix production and cartilage repair in vivo.

Broader Applications

These studies suggest the possibility of using such modified biomaterial not only with chondrocytes, but with other cell types.

New Approaches to Drug Delivery

The approach of controlling growth factor binding, by the grafting of small peptides for biomaterials represents an important new approach to drug delivery and tissue engineering.

Study Limitations

1
The affinity for IGF-I was lower than that for full length of IGFBP-5.
2
The significant enhancement of IGF-I binding by the addition of a short peptide may provide a template for targeted modification of biomaterials for growth factor binding.
3
Charge based interaction may play a role in aiding binding.

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