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Clinical Orthopaedics and Related Research®

Published in:

01-10-2011 | Symposium: Clinically Relevant Strategies for Treating Cartilage and Meniscal Pathology

Growth Factor Delivery Through Self-assembling Peptide Scaffolds

Authors: Rachel E. Miller, PhD, Paul W. Kopesky, PhD, Alan J. Grodzinsky, ScD

Published in: Clinical Orthopaedics and Related Research® | Issue 10/2011

Abstract

Background

The best strategy for delivering growth factors to cells for the purpose of cartilage tissue engineering remains an unmet challenge. Tethering biotinylated insulin-like growth factor-1 (bIGF-1) to the self-assembling peptide scaffold (RADA)₄ effectively delivers bioactive bIGF-1 to cardiac tissue.

Questions/purposes

We therefore asked whether: (1) soluble bIGF-1 could stimulate proteoglycan production by chondrocytes; (2) bIGF-1 could be adsorbed or tethered to the self-assembling peptide scaffold (KLDL)₃; (3) adsorbed or tethered bIGF-1 could stimulate proteoglycan production; and (4) transforming growth factor-β1 (TGF-β1) could be adsorbed or tethered and stimulate proteoglycan production by bone marrow stromal cells (BMSCs).

Methods

Chondrocytes or BMSCs were encapsulated in (KLDL)₃. The growth factors were (1) delivered solubly in the medium; (2) adsorbed to (KLDL)₃; or (3) tethered to (KLDL)₃ through biotin-streptavidin bonds. Fluorescently tagged streptavidin was used to determine IGF-1 kinetics; sGAG and DNA content was measured.

Results

Soluble bIGF-1 stimulated comparable sGAG accumulation as soluble IGF-1. Tethering IGF-1 to (KLDL)₃ increased retention of IGF-1 in (KLDL)₃ compared with adsorption, but neither method increased sGAG or DNA accumulation above control. Adsorbing TGF-β1 increased proteoglycan accumulation above control, but tethering did not affect sGAG levels.

Conclusions

Although TGF-β1 can be effectively delivered by adsorption to (KLDL)₃, IGF-1 cannot. Additionally, although tethering these factors provided long-term sequestration, tethering did not stimulate proteoglycan production.

Clinical Relevance

Tethering growth factors to (KLDL)₃ results in long-term delivery, but tethering does not necessarily result in the same bioactivity as soluble delivery, indicating presentation of proteins is vital when considering a delivery strategy.

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Title: Growth Factor Delivery Through Self-assembling Peptide Scaffolds
Authors: Rachel E. Miller, PhD
Paul W. Kopesky, PhD
Alan J. Grodzinsky, ScD
Publication date: 01-10-2011
Publisher: Springer-Verlag
Published in: Clinical Orthopaedics and Related Research® / Issue 10/2011
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI: https://doi.org/10.1007/s11999-011-1891-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Growth Factor Delivery Through Self-assembling Peptide Scaffolds

Abstract

Background

Questions/purposes

Methods

Results

Conclusions

Clinical Relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Questions/purposes

Methods

Results

Conclusions

Clinical Relevance

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