From fish skin to skin substitute

Kerecis intact fish-skin technology

Fish Skin Technology

Because no disease-transfer risk exists between cold-water fish and humans, the Kerecis patented fish skin is only gently processed and retains its similarity to human skin. Compared to mammalian-based skin substitutes, fish skin offers improved economics and clinical performance and no cultural constraints on usage.

Most tissue-transplant products are based on tissues of human and porcine origin. These are not ideal substitutes because heavy processing is needed to eliminate the risk of disease transmission. This harsh, anti-viral treatment removes most of the material’s natural components, making it dissimilar to human skin.

Listen to what leading authorities in the wound care field have to say about fish skin

Click on CC in the video for English captions

Dr. David Armstrong – DPM, MD, PhD

Dr. Windy Cole – DPM

Dr. Michael J. Lacqua – MD

Dr. John C. Lantis II – MD, FACS

Key technical advantages

  • No cultural or religious barriers to clinician/patient acceptance
  • Easier to use, with larger, thicker sheets (no need for multi-layer grafts)
  • Non allergenic and bio-compatible
  • No known risk of disease transfer
  • Enhanced cell proliferation and vascularization
  • Adjustable rate of absorption into the surrounding tissue

Fish skin has been shown to be more similar in structure to human skin than anti-viral–processed skin substitutes. Because there is no risk of disease transmission, fish skin is only minimally processed, preserving its structure and components. In a double-blind, comparative, randomized controlled clinical trial (N=162), fish skin favorably compared with mammalian skin substitutes.

Application include reconstructing the skin in burn, chronic wounds, and oral wounds, hernia repair, breast reconstruction, and dura mater reconstruction.

Other tissue-transplant products are based on tissues of human and porcine origin. Mammalian tissue carries the risk of disease transmission to humans that is nonexistent from the Atlantic cod to humans. The FDA has strict requirements on tissues from farm animals including viral inactivation methods involving treatment with detergents that remove lipids from the tissues and denature the native structure leaving behind only the most insoluble collagens. Products from human tissues like skin and dehydrated human amnion/chorion membrane call for extensive use of antibiotics to reduce bioburden. The acellular fish skin graft is not subject to this harsh treatment, leaving a more naturally intact product with its associated benefits.

The fish are caught in the pristine waters of North Atlantic Ocean off the township of Isafjordur, on the northwest coast of Iceland. Each and every batch of raw materials is tracked to ensure product quality. The fish skin is processed using a proprietary method that preserves its structure and lipid composition.

Kerecis has demonstrated its proficiency in creating lipid-containg tissue matrices from fish skin, and it has been shown that the material is safe, non-toxic and structurally sound. The company is focused on developing medical device applications with a predicated high return on investment and a low-to-medium cost of development.

Intellectual Property

Kerecis has been awarded multiple patents protecting the core technology in the U.S. and other countries, and several more applications are pending. Kerecis is committed to building a substantial patent portfolio protecting the company´s intellectual property so that revenue from manufacturing and licensing activities can be maximized over the invention’s lifetime.

Technical Basis

Our Omega3 rich fish skin contains lipids, glycans, elastin and proteins.

The lipids include sterols, fat-soluble vitamins, and phospholipids as well as polyunsaturated fatty acids (Omega3). The health benefits of polyunsaturated fatty acids have long been recognized and their positive impact on health is on sound scientific footing [1]. These favorable effects are in large part mediated by the Omega3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are found in high concentration in fish oil. One reason why wounds fail to heal is the shortage of lipids that are formed in the Golgi apparatus of the keratinocytes [2].

Fish Skin

The fish skin’s protein composition closely resembles that of human skin and the porous microstructure provides a scaffold for efficient ingrowth of dermal cells and capillaries. In addition, fish skin is uniquely rich in the polyunsaturated Omega3 fatty acids EPA and DHA, which are known for their anti-inflammatory properties. Significant biological activity has been demonstrated [3, 4].

Fish skin possesses many of the same features as mammalian skin, among them an appropriate surface chemistry and microstructures that facilitate cellular attachment, competent mechanical strength and biodegradation rate without undesirable by-products [6, 7, 8].

References
1. Harris WS, Mozaffarian D, Lefevre M, Toner CD, Colombo J, et al. Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids. J Nutr. 2009;139:804S-819S.
2. Feingold KR. Thematic review series: Skin lipids. The role of epidermal lipids in cutaneous Permeability barrier homeostasis. J Lipid Res. 2007;48:2531-2546.
3. Badylak SF, Freytes DO, Gilbert TW. Extracellular matrix as a biological scaffold material: Structure and function. Acta Biomater. 2009;5:1-13.
4. Reing JE, Zhang L, Myers-Irvin J, Cordero KE, Freytes DO, et al. Degradation products of extracellular matrix affect cell migration and proliferation. Tissue Eng Part A. 2009;15:605-614.
5. Lin CC, Ritch R, Lin SM, Ni MH, Chang YC, et al. A new fish-scale-derived scaffold for corneal regeneration. Eur Cell Mater. 2010;19:50-57.
6. Hawkes JW. The structure of fish skin. I. General Organization. Cell Tissue Res. 1974;149:147-158.
7. Le Guellec D, Morvan-Dubois G, Sire JY. Skin development in bony fish with particular emphasis on collagen deposition in the dermis of the zebrafish (Danio rerio). Int J Dev Biol. 2004;48:217-231.
8. Rakers S, Gebert M, Uppalapati S, Meyer W, Maderson P, et al. ‘Fish Matters’: the relevance of fish-skin biology to unvestigative dermatology. Exp Dermatol. 2010;19:313-324.