Fish Skin Grafts Omega3 Fatty Acids are Precursors for the Specialized Pro-Resolving Mediators that Drive Inflammation Resolution

Background:

Most cellular and tissue based products (CTPs) are derived from livestock or human amniotic membranes# and require heavy processing due to disease transmission risk. This removes bioactive components and denatures microstructure, leaving behind only a matrix of the most insoluble collagens.(1,2)

Fish skin grafts* CTPs undergo far gentler processing methods since they (Gadus morhua) do not pose a disease transmission risk to humans,(3) preserving bioactive components and skin-for-skin microstructure.(4,5)

Fish skin grafts* are rich in omega-3 EPA and DHA fatty acids, necessary for biosynthesis of the specialized pro-resolving lipid mediators (SPMs) that orchestrate inflammation resolution and are lacking in chronic wounds.(6,7)

Aim: 1) To compare the lipid content and profile in fish skin grafts* with human skin and amnion membrane# and collagen matrix CTP. 2) Study the effects of fish skin* lipids on HaCat migration SPMs pathways.

Methods: Lipids were extracted using liquid-liquid extraction. Fatty acid analysis was done with gas chromatography and lipid analysis with liquid chromatography-mass spectrometry.

Wound healing assay was done with the Culture Insert 2 well (Ibidi GmbH) and carried out using HaCaT keratinocytes (ATCC® PCS-200-010™). The qPCR was done with PrimeTime® Assay

Kit.

Results: Fish skin grafts contain >30 times higher ratio of Omega-3/total fatty acids and distinctively different lipid profile compared to the other CTPs. Fish skin lipids induce the migration of HaCat keratinocytes and the transcription of ALOX-15 SPMs forming lioxygenase.

Conclusion: Clinical evidence for the use of fish skin grafts is growing and has shown faster healing in a comparative RCT,(3) chronic wounds,(8,9) reduction in bacterial infiltration(4) and pain.(9)

The results here along with other pre-clinical data(4,5) show that the clinical efficacy of the fish skin grafts can be attributed to the unique combination of preserved skin-for-skin microstructure and its naturally occurring omega-3 fatty acids.