CHP Staining: Unlocking a New Therapeutic Strategy for Fibrosis
Fibrosis, the pathological accumulation of collagen and other ECM components, is a major health concern implicated in an estimated ⅓ of all natural deaths. While current anti-fibrotic drugs aim to slow progression, advanced fibrosis is often left untreated, leaving transplantation the only remaining option in many cases.
A new therapeutic approach is focusing on collagen denaturation to restore tissue flexibility. This strategy relies on heat: when collagen is heated above about ~65 C, its stable triple-helix structure unwinds, denaturing into a random molecular structure with significantly less tensile strength.
To develop this therapy and confirm its viability, researchers need a precise and minimally invasive heat source, and a way to confirm that they are denaturing scar tissue without causing excessive damage, which in itself could contribute to fibrotic remodeling. Recently, researchers in Japan have examined using a 450nm fractional laser as their heat source, and used Collagen Hybridizing Peptides (CHPs) to visually detect molecular evidence of thermal collagen denaturation post-laser irradiation.
Collagen Hybridizing Peptides are synthetic probes that mimic the Gly-X-Y sequence of collagen molecules to exclusively bind to denatured collagen strands (via heat, mechanical damage, enzymatic degradation, etc.)
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The unique abilities of CHPs were essential for two main reasons. First, the researchers needed to identify ideal energy levels and spot densities for their laser. Collagen Hybridizing Peptide staining helped them achieve this by providing a clear, visual readout of where denaturation occurred. This enabled researchers to quantitatively compare the thermal denaturation ratio of various laser settings & optimize their parameters to induce sufficient thermal denaturation while minimizing tissue loss.
Second, CHP staining provided the molecular evidence necessary to correlate the mechanism of their therapy (collagen denaturation) with their proposed outcome (tissue compliance) measured by a drop in Young’s modulus via tensile testing. The researchers confirmed that fractional laser irradiation successfully enhanced the flexibility of fibrotic tissue models (bovine achilles tendon):
The use of CHP staining was crucial for providing the molecular-level validation that the fractional laser’s thermal effect did cause targeted collagen denaturation, solidifying this study as a significant step towards developing new, localized, minimally invasive treatments for fibrotic scar tissue.
- 22.1% for a 3 dots/mm^2 pattern at 110mJ/dot
- 23% for a 6 dot/mm^2 pattern at 99mJ/dot
- 32% for a 12 dots/mm^2 pattern at 84mJ/dot
Want to learn more about how Collagen Hybridizing Peptides can advance your research on tissue remodeling? Explore our full range of CHP probes here, or reach out to us directly to schedule an introductory call!
