Omega-3 Acellular Fish Skin Grafts for Chronic and Complicated Wounds: A Systematic Review of Efficacy and Safety

Mohd. Ashif Khan; Sonali Karhana

doi:10.5826/dpc.1502a4945

Omega-3 Acellular Fish Skin Grafts for Chronic and Complicated Wounds: A Systematic Review of Efficacy and Safety

Authors

Mohd. Ashif Khan Jamia Hamdard
Sonali Karhana Jamia Hamdard

Keywords:

dermatology, Wound healing, chronic wounds, diabetic foot ulcer

Abstract

Introduction: A systematic review was conducted to investigate the efficacy of acellular fish skin grafts (AFSGs), for the treatment of complicated wounds. AFSGs can be used as a regenerative and antimicrobial tool for healing complicated wounds but clinical evidence remains unclear.

Objective: This systematic review aims to summarize the efficacy of AFSGs on complicated wounds using evidence from existing published studies.

Methods: Electronic databases like PubMed, ScienceDirect, Google Scholar and Clinicaltrials.gov were searched for relevant literature reporting on the efficacy of AFSGs for wound healing. Based on the inclusion and exclusion criteria, nine studies were selected for data extraction. The quality of the articles was evaluated using the RoB 2 and ROBINS-I tools.

Results: Existing evidence shows that AFSGs accelerate wound healing, reduce pain, prevent antibiotic administration and cause no autoimmune reactions. The total reepithelialisation time for diabetic foot ulcers (DFUs) was observed between 15 ± 8 weeks, depending on the severity of the ulcers. Acute biopsy wounds were healed within 3.75 ± 0.25 weeks. AFSGs showed significantly better effects than standard-of-care therapies. However, instances of rashes, erythema, pain, and hypergranulation were reported when AFSGs were applied to biopsy wounds.

Conclusion: Overall, the evidence obtained in this systematic review indicates that AFSGs represent a clinically and financially effective option for the treatment of wounds when compared with conventional alternatives.

Author Biography

Sonali Karhana, Jamia Hamdard

Department of Translational and Clinical Research, School of Chemical and Life Sciences

References

R. Thakur, N. Jain, R. Pathak, and S. S. Sandhu, “Practices in wound healing studies of plants,” Evid Based Complement Alternat Med, vol. 2011, 2011, DOI: 10.1155/2011/438056.

C. K. Sen, “Human Wound and Its Burden: Updated 2020 Compendium of Estimates,” https://home.liebertpub.com/wound, vol. 10, no. 5, pp. 281–292, Mar. 2021, DOI: 10.1089/WOUND.2021.0026.

M. Baba, W. A. Davis, P. E. Norman, and T. M. E. Davis, “Temporal changes in the prevalence and associates of foot ulceration in type 2 diabetes: The Fremantle Diabetes Study,” J Diabetes Complications, vol. 29, no. 3, pp. 356–361, Apr. 2015, DOI: 10.1016/J.JDIACOMP.2015.01.008.

D. G. ARMSTRONG, null D.P.M., and L. A. LAVERY, “Diabetic Foot Ulcers: Prevention, Diagnosis and Classification,” Am Fam Physician, vol. 57, no. 6, pp. 1325–1332, Mar. 1998, Accessed: Nov. 17, 2022. [Online]. Available: https://www.aafp.org/pubs/afp/issues/1998/0315/p1325.html

M. Á. Tresierra-Ayala and A. García Rojas, “Association between peripheral arterial disease and diabetic foot ulcers in patients with diabetes mellitus type 2,” Medicina Universitaria, vol. 19, no. 76, pp. 123–126, Jul. 2017, DOI: 10.1016/J.RMU.2017.07.002.

M. Asaf, N. Salim, M. Tuffaha, and N. A. Salim, “Challenging the Use of Bandage Compression as the Baseline for Evaluating the Healing Outcomes of Venous Leg Ulcer-Related Compression Therapies in the Community and Outpatient Setting: An Integrative Review,” Dubai Medical Journal, vol. 1, no. 1–4, pp. 19–25, Nov. 2018, DOI: 10.1159/000494217.

J. Spiliotis et al., “Wound dehiscence: is still a problem in the 21th century: a retrospective study,” World Journal of Emergency Surgery, vol. 4, no. 1, p. 12, 2009, DOI: 10.1186/1749-7922-4-12.

V. K. Shukla, M. A. Ansari, and S. K. Gupta, “Wound healing research: A perspective from India,” International Journal of Lower Extremity Wounds, vol. 4, no. 1, pp. 7–8, Mar. 2005, DOI: 10.1177/1534734604273660.

A. P. Veith, K. Henderson, A. Spencer, A. D. Sligar, and A. B. Baker, “Therapeutic strategies for enhancing angiogenesis in wound healing,” Adv Drug Deliv Rev, vol. 146, pp. 97–125, Jun. 2019, DOI: 10.1016/j.addr.2018.09.010.

Y. Niu, Q. Li, Y. Ding, L. Dong, and C. Wang, “Engineered delivery strategies for enhanced control of growth factor activities in wound healing,” Adv Drug Deliv Rev, vol. 146, pp. 190–208, Jun. 2019, DOI: 10.1016/j.addr.2018.06.002.

E. M. Tottoli, R. Dorati, I. Genta, E. Chiesa, S. Pisani, and B. Conti, “Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration,” Pharmaceutics, vol. 12, no. 8, p. 735, Aug. 2020, DOI: 10.3390/pharmaceutics12080735.

S. Jacobsen, “Topical Wound Treatments and Wound‐Care Products,” in Equine Wound Management, Wiley, 2016, pp. 75–103. DOI: 10.1002/9781118999219.ch5.

K. Barrigah-Benissan, J. Ory, A. Sotto, F. Salipante, J.-P. Lavigne, and P. Loubet, “Antiseptic Agents for Chronic Wounds: A Systematic Review,” Antibiotics, vol. 11, no. 3, p. 350, Mar. 2022, DOI: 10.3390/antibiotics11030350.

M. Abd Elhakeem, N. Zaher, A. Ezzat, A. Ashraf, and O. Seif, “Methacrylate Powder Dressing in Traumatic, Pressure sore, Venous ulcers and Burn Wounds Healing,” Benha Medical Journal, vol. 0, no. 0, pp. 0–0, Aug. 2022, DOI: 10.21608/bmfj.2022.128226.1560.

S. A. Chowdhry, “Use of oxidized regenerated cellulose (ORC)/collagen/silver-ORC dressings to help manage skin graft donor site wounds,” JPRAS Open, vol. 22, pp. 33–40, Dec. 2019, DOI: 10.1016/j.jpra.2019.08.001.

E. B. Jude, J. Apelqvist, M. Spraul, and J. Martini, “Prospective randomized controlled study of Hydrofiber® dressing containing ionic silver or calcium alginate dressings in non‐ischaemic diabetic foot ulcers,” Diabetic Medicine, vol. 24, no. 3, pp. 280–288, Mar. 2007, DOI: 10.1111/j.1464-5491.2007.02079.x.

P. Muangman, C. Pundee, S. Opasanon, and S. Muangman, “A prospective, randomized trial of silver containing hydrofiber dressing versus 1% silver sulfadiazine for the treatment of partial thickness burns,” Int Wound J, vol. 7, no. 4, pp. 271–276, Aug. 2010, DOI: 10.1111/j.1742-481X.2010.00690.x.

R. G. Frykberg and J. Banks, “Challenges in the Treatment of Chronic Wounds,” Adv Wound Care (New Rochelle), vol. 4, no. 9, pp. 560–582, Sep. 2015, DOI: 10.1089/wound.2015.0635.

D.-C. Ding, Y.-H. Chang, W.-C. Shyu, and S.-Z. Lin, “Human Umbilical Cord Mesenchymal Stem Cells: A New Era for Stem Cell Therapy,” Cell Transplant, vol. 24, no. 3, pp. 339–347, Mar. 2015, DOI: 10.3727/096368915X686841.

N. Kosaric, H. Kiwanuka, and G. C. Gurtner, “Stem cell therapies for wound healing,” Expert Opin Biol Ther, vol. 19, no. 6, pp. 575–585, Jun. 2019, DOI: 10.1080/14712598.2019.1596257.

“Acellular Dermal Matrix (ADM) Products Used in Implant-Based Breast Reconstruction Differ in Complication Rates: FDA Safety Communication | FDA.” Accessed: Nov. 18, 2022. [Online]. Available: https://www.fda.gov/medical-devices/safety-communications/acellular-dermal-matrix-adm-products-used-implant-based-breast-reconstruction-differ-complication

C. V. Ellis and D. A. Kulber, “Acellular Dermal Matrices in Hand Reconstruction,” Plast Reconstr Surg, vol. 130, pp. 256S-269S, Nov. 2012, DOI: 10.1097/PRS.0b013e318265a5cf.

A. Pabst et al., “Biomechanical Characterization of a New Acellular Dermal Matrix for Oral Soft Tissue Regeneration,” Journal of Investigative Surgery, vol. 35, no. 6, pp. 1296–1303, Jun. 2022, DOI: 10.1080/08941939.2022.2047245.

T. H. Kim, J. H. Park, H. G. Jeong, and S. Y. Wee, “The Utility of Novel Fish-Skin Derived Acellular Dermal Matrix (Kerecis) as a Wound Dressing Material,” Journal of Wound Management and Research, vol. 17, no. 1, pp. 39–47, Feb. 2021, DOI: 10.22467/JWMR.2020.01228.

T. O’Donnell, M. Passman, … W. M.-J. of vascular, and undefined 2014, “Management of venous leg ulcers: clinical practice guidelines of the Society for Vascular Surgery® and the American Venous Forum,” jvascsurg.org, Accessed: Nov. 18, 2022. [Online]. Available: https://www.jvascsurg.org/article/S0741-5214(14)00851-9/abstract

S. Rakers et al., “‘Fish matters’: the relevance of fish skin biology to investigative dermatology,” Exp Dermatol, vol. 19, no. 4, pp. 313–324, Apr. 2010, DOI: 10.1111/j.1600-0625.2009.01059.x.

M. Sun, J. Dong, Y. Xia, and R. Shu, “Antibacterial activities of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against planktonic and biofilm growing Streptococcus mutans,” Microb Pathog, vol. 107, pp. 212–218, Jun. 2017, DOI: 10.1016/j.micpath.2017.03.040.

M. Sun, Z. Zhou, J. Dong, J. Zhang, Y. Xia, and R. Shu, “Antibacterial and antibiofilm activities of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against periodontopathic bacteria,” Microb Pathog, vol. 99, pp. 196–203, Oct. 2016, DOI: 10.1016/j.micpath.2016.08.025.

F. Bassetto, C. Scarpa, and F. Facchin, “Complicated Wounds,” in Textbook of Plastic and Reconstructive Surgery, Cham: Springer International Publishing, 2022, pp. 27–38. DOI: 10.1007/978-3-030-82335-1_3.

M. L. B. Sørensen, R. B. Jansen, T. Wilbek Fabricius, B. Jørgensen, and O. L. Svendsen, “Healing of Diabetic Foot Ulcers in Patients Treated at the Copenhagen Wound Healing Center in 1999/2000 and in 2011/2012,” J Diabetes Res, vol. 2019, pp. 1–9, Sep. 2019, DOI: 10.1155/2019/6429575.

A. C. Yelland et al., “Impact of case‐mix adjustment on observed variation in the healing of diabetic foot ulcers at 12 weeks using data from the National Diabetes Foot Care Audit of England and Wales: A cohort study,” Diabetic Medicine, vol. 40, no. 1, Jan. 2023, DOI: 10.1111/dme.14959.

T. Zehnder and M. Blatti, “Faster Than Projected Healing in Chronic Venous and Diabetic Foot Ulcers When Treated with Intact Fish Skin Grafts Compared to Expected Healing Times for Standard of Care: An Outcome-Based Model from a Swiss Hospital,” International Journal of Lower Extremity Wounds, 2022, DOI: 10.1177/15347346221096205.

B. Dorweiler et al., “The marine Omega3 wound matrix for treatment of complicated wounds: A multicenter experience report,” Gefasschirurgie, vol. 23, pp. 46–55, Aug. 2018, DOI: 10.1007/S00772-018-0428-2.

A. E. Rivera and J. M. Spencer, “Clinical aspects of full-thickness wound healing,” Clin Dermatol, vol. 25, no. 1, pp. 39–48, Jan. 2007, DOI: 10.1016/j.clindermatol.2006.10.001.

T. Woodrow, T. Chant, and H. Chant, “Treatment of diabetic foot wounds with acellular fish skin graft rich in omega-3: a prospective evaluation,” https://DOI.org/10.12968/jowc.2019.28.2.76, vol. 28, no. 2, pp. 76–80, Feb. 2019, DOI: 10.12968/JOWC.2019.28.2.76.

E. Lullove, B. Liden, … P. M.-… : a C. of, and undefined 2022, “Evaluating the effect of omega-3-rich fish skin in the treatment of chronic, nonresponsive diabetic foot ulcers: penultimate analysis of a multicenter, prospective,” europepmc.org, Accessed: Nov. 29, 2022. [Online]. Available: https://europepmc.org/article/med/35797557

R. S. Kirsner et al., “Fish skin grafts compared to human amnion/chorion membrane allografts: A double‐blind, prospective, randomized clinical trial of acute wound healing,” Wiley Online Library, vol. 28, no. 1, pp. 75–80, Jan. 2019, DOI: 10.1111/wrr.12761.

B. T. Baldursson, H. Kjartansson, F. Konrádsdóttir, P. Gudnason, G. F. Sigurjonsson, and S. H. Lund, “Healing rate and autoimmune safety of full-thickness wounds treated with fish skin acellular dermal matrix versus porcine small-intestine submucosa: A noninferiority study,” International Journal of Lower Extremity Wounds, vol. 14, no. 1, pp. 37–43, Mar. 2015, DOI: 10.1177/1534734615573661.

J. Yoon et al., “Wound healing ability of acellular fish skin and bovine collagen grafts for split-thickness donor sites in burn patients: Characterization of acellular grafts and clinical,” Elsevier, Accessed: Nov. 29, 2022. [Online]. Available: https://www.sciencedirect.com/science/article/pii/S0141813022002914

H. Luze, S. P. Nischwitz, C. Smolle, R. Zrim, and L.-P. Kamolz, “The Use of Acellular Fish Skin Grafts in Burn Wound Management—A Systematic Review,” Medicina (B Aires), vol. 58, no. 7, p. 912, Jul. 2022, DOI: 10.3390/medicina58070912.

S. Magnusson et al., “Acellular Fish Skin Grafts and Pig Urinary Bladder Matrix Assessed in the Collagen-Induced Arthritis Mouse Model,” Int J Low Extrem Wounds, vol. 17, no. 4, pp. 275–281, Dec. 2018, DOI: 10.1177/1534734618802899.

E. S. Mauer, E. A. Maxwell, C. J. Cocca, J. Ganjei, and D. Spector, “Acellular fish skin grafts for the management of wounds in dogs and cats: 17 cases (2019–2021),” Am J Vet Res, vol. 83, no. 2, pp. 188–192, Feb. 2022, DOI: 10.2460/ajvr.21.09.0140.

A. de Souza et al., “Fish collagen for skin wound healing: a systematic review in experimental animal studies,” Cell Tissue Res, vol. 388, no. 3, pp. 489–502, Jun. 2022, DOI: 10.1007/s00441-022-03625-w.

D. Li et al., “Evaluation of a novel tilapia-skin acellular dermis matrix rationally processed for enhanced wound healing,” Materials Science and Engineering: C, vol. 127, p. 112202, Aug. 2021, DOI: 10.1016/j.msec.2021.112202.

K. Lv, L. Wang, X. He, W. Li, L. Han, and S. Qin, “Application of Tilapia Skin Acellular Dermal Matrix to Induce Acute Skin Wound Repair in Rats,” Front Bioeng Biotechnol, vol. 9, Feb. 2022, DOI: 10.3389/fbioe.2021.792344.

C. Winters, C. is P.-D. F. J, and undefined 2018, “Wound dehiscence on a diabetic patient with hemophilia and high risk of further amputation successfully healed with omega 3 rich fish skin: a case report,” diabetesonthenet.com, vol. 21, no. 3, 2018, Accessed: Dec. 01, 2022. [Online]. Available: https://diabetesonthenet.com/wp-content/uploads/pdf/dotn5af79c6d5de192c212a36c077c19189a.pdf

K. Alam and S. L. A. Jeffery, “Acellular Fish Skin Grafts for Management of Split Thickness Donor Sites and Partial Thickness Burns: A Case Series,” Mil Med, vol. 184, no. Supplement_1, pp. 16–20, Mar. 2019, DOI: 10.1093/MILMED/USY280.

C. Daidone, N. Salim, L. Smith, and A. Raza, “The Role of Fish Skin Xenografts in Healing Complex Wounds: A Brief Case Report,” Cureus, Mar. 2024, DOI: 10.7759/cureus.56156.

latifi Rifat and Abbas Smiley, “acellelar fish skin garft use in open abdomen management,” Surgical Technology Internationsl, vol. 42, 2023.

D. le Guellec, G. Morvan-Dubois, J. S.-I. J. of, and undefined 2003, “Skin development in bony fish with particular emphasis on collagen deposition in the dermis of the zebrafish (Danio rerio).,” ijdb.ehu.es, vol. 48, pp. 217–231, 2004, Accessed: Dec. 01, 2022. [Online]. Available: http://www.ijdb.ehu.es/web/paper/15272388/skin-development-in-bony-fish-with-particular-emphasis-on-collagen-deposition-in-the-dermis-of-the-zebrafish-danio-rerio

S. R. Van Doren, “Matrix metalloproteinase interactions with collagen and elastin,” Matrix Biology, vol. 44–46, pp. 224–231, May 2015, DOI: 10.1016/j.matbio.2015.01.005.

J. C. McDaniel, K. Massey, and A. Nicolaou, “Fish oil supplementation alters levels of lipid mediators of inflammation in microenvironment of acute human wounds,” Wound Repair and Regeneration, vol. 19, no. 2, pp. 189–200, Mar. 2011, DOI: 10.1111/j.1524-475X.2010.00659.x.

S. Magnusson, B. Baldursson, … H. K.-M., and undefined 2017, “Regenerative and antibacterial properties of acellular fish skin grafts and human amnion/chorion membrane: implications for tissue preservation in combat casualty,” academic.oup.com, Accessed: Dec. 01, 2022. [Online]. Available: https://academic.oup.com/milmed/article-abstract/182/suppl_1/383/4209412

E. Lima-Junior, N. Picollo, and M. Miranda, “Uso da pele de tilápia (Oreochromis niloticus), como curativo biológico oclusivo, no tratamento de queimaduras,” Rev Bras Queimaduras, vol. 16, no. 1, pp. 10–17, 2017, Accessed: Dec. 01, 2022. [Online]. Available: https://repositorio.ufc.br/handle/riufc/28917

P. Brown, R. G. Will, R. Bradley, D. M. Asher, and L. Detwiler, “Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: background, evolution, and current concerns.,” Emerg Infect Dis, vol. 7, no. 1, p. 6, 2001, DOI: 10.3201/EID0701.010102.

H. Kjartansson, I. Olafsson, … S. K.-O. J. of M., and undefined 2015, “Use of acellular fish skin for dura repair in an ovine model: a pilot study,” scirp.org, Accessed: Dec. 01, 2022. [Online]. Available: https://www.scirp.org/html/4-2080131_60730.htm

C. Winters, R. S. Kirsner, D. J. Margolis, and J. C. Lantis, “Cost Effectiveness of Fish Skin Grafts Versus Standard of Care on Wound Healing of Chronic Diabetic Foot Ulcers: A Retrospective Comparative Cohort Study.,” Wounds, vol. 32, no. 10, pp. 283–290, Oct. 2020.

S. Karhana, S. Dabral, A. Garg, A. Bano, N. Agarwal, and Mohd. A. Khan, “Network pharmacology and molecular docking analysis on potential molecular targets and mechanism of action of BRAF inhibitors for application in wound healing,” J Cell Biochem, vol. 124, no. 7, pp. 1023–1039, Jul. 2023, DOI: 10.1002/jcb.30430.

A. Garg et al., “Network pharmacology and molecular docking study-based approach to explore mechanism of benzimidazole-based anthelmintics for the treatment of lung cancer,” J Biomol Struct Dyn, pp. 1–22, Sep. 2023, DOI: 10.1080/07391102.2023.2258419.

X. Zhang et al., “Current Progress and Outlook of Nano-Based Hydrogel Dressings for Wound Healing,” Pharmaceutics, vol. 15, no. 1, p. 68, Dec. 2022, DOI: 10.3390/pharmaceutics15010068.

N. Kosaric, H. Kiwanuka, and G. C. Gurtner, “Stem cell therapies for wound healing,” Expert Opin Biol Ther, vol. 19, no. 6, pp. 575–585, Jun. 2019, DOI: 10.1080/14712598.2019.1596257.