IGF-1 Potently Enhances Collagen Deposition and Mechanical Strength in Dermal Tissues, Even from Older Donors

Tissue engineering offers a promising avenue for repairing damaged tissues, but age-related declines in extracellular matrix (ECM) deposition by stromal cells often compromise the mechanical integrity of reconstructed tissues. This is particularly critical for conditions like stress urinary incontinence (SUI), which predominantly affects women over 50 years of age. Current treatments often involve synthetic midurethral slings, which have raised concerns regarding safety and long-term tolerance. There's a clear need for strategies to enhance the robustness of biological tissue constructs, and insulin-like growth factor 1 (IGF-1) is a known regulator of cell growth and tissue repair.

Researchers investigated biochemical modulation to enhance collagen deposition and mechanical properties in self-assembled dermal tissues. They utilized dermal fibroblasts derived from female donors of different ages, culturing them in the presence of ascorbic acid. The study evaluated the effects of hormonal supplementation (β-estradiol, progesterone), metabolic and hypoxia-related stimuli, and insulin-like growth factor 1 (IGF-1) signaling activation. Primary endpoints included collagen quantification, histological analyses, and mechanical testing to assess tissue robustness.

Fibroblasts from younger donors inherently deposited significantly more collagen than those from older female donors. Among all tested conditions, IGF-1 emerged as a potent enhancer, markedly increasing collagen deposition in a dose-dependent manner. This effect was observed even in fibroblasts from women over 50 years of age. In contrast, β-estradiol and progesterone had no significant effect on collagen content. While β-estradiol did slightly increase tissue thickness, only IGF-1 supplementation led to substantial improvements across multiple mechanical parameters.

IGF-1 supplementation resulted in substantial improvements in perforation strength, stiffness, displacement at break, and toughness of the reconstructed tissues.