Engineered insulin-like growth factor-1 for improved smooth muscle regeneration

Area of Science:

• Biomaterials Engineering
• Regenerative Medicine
• Molecular Biology

Background:

• Sustained local delivery of insulin-like growth factor-1 (IGF-1) remains a clinical challenge.
• IGF-1 is a potent mitogen crucial for cell proliferation and tissue repair.

Purpose of the Study:

• To develop an engineered IGF-1 variant for sustained local delivery via fibrin matrices.
• To assess the bioactivity and efficacy of the engineered IGF-1 in promoting smooth muscle cell (SMC) regeneration.

Main Methods:

• Recombinant fusion of IGF-1 with an alpha(2)-plasmin inhibitor (α(2)PI(1-8)) tag for fibrin incorporation.
• In vitro bioactivity assays using urinary tract-derived cells and 2D/3D cell culture models.
• In vivo studies in rat bladder lesion models to evaluate SMC proliferation and tissue response.

Main Results:

• The engineered α(2)PI(1-8)-IGF-1 variant demonstrated equivalent bioactivity to wild-type (WT) IGF-1 in 2D cell studies.
• In 3D fibrin matrices, α(2)PI(1-8)-IGF-1 significantly enhanced SMC proliferation compared to WT IGF-1.
• In vivo, sustained delivery of α(2)PI(1-8)-IGF-1 promoted substantial SMC proliferation and favorable tissue response at 28 days.

Conclusions:

• Engineered IGF-1 covalently incorporated into fibrin matrices allows for sustained local delivery.
• This approach significantly enhances smooth muscle regeneration and host tissue response compared to WT IGF-1.
• The developed method offers a promising strategy for improving regenerative therapies requiring localized growth factor delivery.