professor of surgery icahn school of medicine new york, ny ... · 85 healthy volunteers 170 wounds...
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Professor of SurgeryIcahn School of Medicine
New York, NY USAVice Chair of Surgery
Chief of Vascular/Endovascular SurgeryMt Sinai St Luke’s and West Hospitals
New York, NY USA
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I’m bi-vascular with a strong touch of the cutaneous –
ie: I do open and endovascular surgery – and a lot of wound care;
Approximately – 4-6 major vascular cases a week; 6-8 in patient “wound” cases a week… and 70 outpatient wound patients and 30 vascular patients a week…..
Paid Consultant◦ Acelity, Smith & Nephew, Integra, Pluristem, MediWound, Acton, e-Kare, Kerecis
Principal investigator◦ Acelity, Integra, Smith & Nephew, TissueTech, Pluristem
Grant Support◦ Smith & Nephew, Acelity, Integra
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Remember when to think of a CTP
Understand the characteristics of a (cod) fish skin derived extracellular matrix – where it fits with CTPs
Understand the translational implications of the basic science research to date
Understand the clinical results to date for the use of this fish skin product in treating wounds
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When to use a CTP
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Early adoption of advanced or appropriate care may be more cost-effective than traditional standard practices for decreasing the incidence of lower extremity amputation and may speed healing.2
1. Papanas N, et al. Drug Saf. 2010;33:455-461. 2. Kirsner RS. The standard of care for evaluation and treatment of diabetic foot ulcers.http://www.barry.edu/includes/docs/continuing-medical-education/diabetic.pdf.
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Nicolaides, A. N. Investigation of chronic venous insufficiency: A consensus statement (France, March 5-9, 1997). Circulation, 102: E126-E163, 2000.
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Regenerative Medicine and the Chronic Wound
Get back to the basics – what makes your wound chronic? Proper patient care AND wound bed preparation is vital for
healing success – all DFU’s must be offloaded for 4 weeks – all VLUs compressed
BUT - If DFU wounds haven’t decreased in size by >50% at 4 weeks consider CTP; if VLU haven’t decreased in size by >40% at 4 weeks consider CTP
Poor predictors of outcome: DFU > 4 sq cm; > 1 year in duration; over boney prominence VLU > 12 sq cm;> 1 year in duration; significant co-
morbidities
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• To boost growth factor populations within wounds
• To help convert the wound environment from chronic to acute
• To jump start wound healing in chronic wounds
• To fill soft tissue defects –“filling a pothole”
• To help get coverage over exposed deep structures
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Extracellular matrix (ECM) serves as supporting scaffold for invading cells
Cell adhesion to ECM is a prerequisite for maximal bioactivity of growth factors
ECM molecules and growth factors regulate together cellular processes during wound healing
Fish skin is a xenograft (acellular graft- ADG) that retains the natural ECM structure of the fish dermis
Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing. Briquez PS, Hubbell JA, Martino MM.Adv Wound Care (New Rochelle). 2015 Aug 1;4(8):479-489. Review.
https://www.ncbi.nlm.nih.gov/pubmed/26244104
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CTPEffectiveness
Ease of Use
Availability and Support
Insurance
Wound Parameters
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Fish skin for medical use patented; fish skin consists of cells embedded in a network of non-living tissue
Fish skin is CE Marked and FDA cleared
Proteins and lipids in their natural state
Decellularized and allergenic and bio compatible Source Icelandic Cod
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Unique Components- Living cell donation – with e ECM- Providing an ECM – multiple
potential mechanisms of action and types
- Cyto-attractant therapy
Mechanisms of Action- Provide signals – OR -- Provide ECM structure
Three classes of Cellular and Tissue Based Products (CTPs)
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Mechanisms of ActionProvide ECM structure –Template (less frequent applications)Incorporated into the wound, provide a structural template; while providing mechanical as well other signaling mechanisms
Ex: Fetal Bovine Collagen
Mechanisms of ActionProvide signals –Modulatory (more frequent applications)Not so much incorporated but may; decrease MMP, enhance signaling, “rebalance a wound”
Ex: Piscine skin; Ovine submucosa, Ovine bladder
Ex: Dermal regenerative template
Modulatory to Template
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Two prospective blinded controlled trials in acute wounds
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Acute 4 mm forearm punch biopsies; patients are their own controls
Over the 28-day study period, participants had a total of 7 visits.
On day three, participants were contacted by phone by the trial physician to collect information on the status of their wounds. The participants were seen on days, 7, 14, 18, 21, 25 and 28 for assessment of wound status.
If the treatment material was intact, it was left in the wound. If it had reabsorbed or if treatment material was not visible, new material was applied to the wound.
Standardized digital photographs were taken and healing assessment was performed by four wound healing professionals in an independent, blinded manner.
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Blinded Randomized Clinical Trial 81 Healthy voulunteers 162 wounds fish skin vs SIS
4 mm Forearm punch model Significantly (p=0.041) faster
healing No autoimmune reactions ELISA tests on RF, ANA, ENA,
anti ds-DNA, ANCA, anti-CCP, and anticollagen I and II.
Healing Rate and Autoimmune Safety of Full-Thickness Wounds Treated With Fish Skin Acellular Dermal Matrix Versus Porcine Small-Intestine Submucosa: A
Noninferiority StudyBaldur Tumi Baldursson, MD, PhDHilmar Kjartansson, MD, Fífa Konrádsdóttir, MSc, Palmar Gudnason, MSc,
Gudmundur F. Sigurjonsson, MEng Sigrún Helga Lund, PhD; The International Journal of Lower Extremity Wounds2015, Vol. 14(1) 37 –43
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85 healthy volunteers 170 Wounds85 treated with Fish Skin v. 85 treated with dHACMNo loss of follow up.Their average age was 24.1, with a standard deviation of 4.6 years.
66.7% of the cohort were women.
Primary end pointWounds treated with fish skin healed significantly
faster with a hazard ratio of 2.37 (95% CI: 1.75-3.21) at a p-value of 0.001 over dHACM allograft
treated wounds. JC Lantis II MD, FACS; K Petursdottir, MD; B Baldursson; RS. Kirsner, MD, PHD, FAAD; D Weir, RN, CWON; Double-Blind, Prospective, Randomized Clinical Trial on 170 Acute Wounds Shows Significantly Faster Healing Rate with Intact Fish Skin Compared to Human Amniotic Membrane; APWCA September 6-8, 2018. Baltimore MD
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JC Lantis II MD, FACS; K Petursdottir, MD; B Baldursson; RS. Kirsner, MD, PHD, FAAD; D Weir, RN, CWON; Double-Blind, Prospective, Randomized Clinical Trial on 170 Acute Wounds Shows Significantly Faster Healing Rate with Intact Fish Skin Compared to Human Amniotic Membrane; APWCA September 6-8, 2018. Baltimore MD
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However, the immediate question is: What is the applicability of a study on acute wounds on the treatment decision for chronic wounds?
The aggressive debridement (wound excision or ulcerectomy), which, along with offloading is the centerpiece of the care of diabetic foot ulcers is explicitly or implicitly attempts or is “meant” to return the wound dynamics from a chronic to an acute phase.
Therefore the results on acute wounds may have implications for debrided chronic wounds. Also advantageous in this controlled experiment is that removes some biases inherent with clinical wound studies
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Specifically the Hard to Heal Wounds
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German Case study on 7 patients Marine Omega3 wound matrix for the
treatment of complicated woundsPhlebologie – 2016
Pain reduction in all patients
Complete wound closure in all participantsComplicated wounds-exposed bony segments
Marine Omega3 wound matrix for the treatment of complicated wounds Experiences associated with amputations in the lower limb in diabetic patientsT. T. Trinh; F. Dünschede; C.-F. Vahl; B. Dorweiler; Phlebologie 2016; 45: 93–98
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Retrospective antimicrobial all comers wound study
54 non healing wounds were treated with fish skin grafts* for a period of four weeks and 2 applications on average.
Improvement is defined as >20% reduction of wound area.
Data was extracted from the patient records database at the Landspitali University Hospital in Reykjavik, Iceland.
Study was approved by the National Bioethics Committee of Iceland (VSN-15-137).
Antibiotics therapy was not a predetermined endpoint since this was a retrospective study.
Lantis J, Baldursson B, Magnusson S, Kjartansson, Sigurjonsson G. Acellular Fish Skin Graft for Surgical, Trauma, Venous and Arterial and Diabetic Wounds: A retrospective clinical study –– Oral session 17th Congress of the Asian Society for Vascular Surgery, October
20-23, 2016 Singapore
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• Treatment with fish skin grafts* showed a 38% reduction in antibiotics use.
• Overall, 87% of non healing wounds treated with fish skin grafts* either improved or healed after 4 weeks of treatment.
• No wound became worse in the course of the 4 week treatment with the acellular fish skin*.
Wounds that either improved or healed completely:
• 83% (10) of surgical or traumatic wounds • 92% (25) of venous leg ulcers • 71% (5) of arterial ulcers • 87% (7) of diabetic foot ulcers
Lantis J, Baldursson B, Magnusson S, Kjartansson, Sigurjonsson G. Acellular Fish Skin Graft for Surgical, Trauma, Venous and Arterial and Diabetic Wounds: A retrospective clinical study – Oral session 17th Congress of the Asian Society for Vascular Surgery, October 20-23, 2016 Singapore
Improved 62%
Healed13%
Not respondin
g25%
Arterial Ulcers
Improved 37%
Healed50%
Not responding
13%
Diabetic Foot Ulcers
Improved 70%
Healed22%
Not responding
8%
Venous or mixed venous/arterial
Improved 41%
Healed42%
Not responding
17%
Surgical/Trauma Wounds
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Antibiotics-Before Antibiotics-After
%RESULTSOmega3 Fish Skin* for Chronic Wounds
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Percentage of wound closure area from baseline after 5 weekly ECM applications in 18 patients with at least one “hard to heal” criteria.
Application of the ECM for 5 sequential weeks, followed by 3 weeks of standard of care;
Secondary wound dressings were applied per their underlying etiology. Wound area, signs of infection were collectedof infection and pain were assessed weekly visits.A Prospective, Postmarket, Compassionate Clinical Evaluation of a Novel Acellular Fish-skin Graft Which Contains Omega-3 Fatty Acids for the Closure of Hard-to-heal Lower Extremity Chronic Ulcers. Yang CK, Polanco TO, Lantis JC 2nd.Wounds. 2016 Apr;28(4):112-8
https://www.ncbi.nlm.nih.gov/pubmed/27071138
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18 patients40% decrease in wound surface area was seen with 5 weekly applications (P
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Table 1. Liklihood of healing by prognostic factors. The table shows the likelihood that a patient with a given prognostic factor or combination of prognostic factors will heal after 20 weeks.1
Table 2. Ulcer related health care cost per episode. Thetable displays the ulcer-related pharmacy, medical and totalcosts per week.2
A cost savings model –“more products should use“
The cost-simulation study was based on a prognostic model for identifying diabetic foot ulcers that are not likely to heal.
The model was generated by data from 27,630 patients with diabetic foot ulcers.1 The model predicts the likelihood of a wound not healing after 20 weeks based on some of all of the following parameters being met:
(1) Size > 2 cm2 (2) Previous duration of wound > 2 months (3) The ulcer grade ≥ 3
The cost per week was then assigned to the two scenarios2 with the additional cost of using the acellular fish skin graft product.
1. Margolis, D. J., Allen-Taylor, L., Hoffstad, O. & Berlin, J. A. Diabetic neuropathic foot ulcers: predicting which ones will not heal. Am. J. Med. 115, 627–631 (2003).
2. Stockl K. et al. Costs of Lower-Extremity Ulcers Among Patients With Diabetes. Diabetes Care. 2004 Sep;27(9):2129-34.
3. Lantis J, Magnusson S, Margolis D Baldursson BT, Kjartansson, G Sigurjonsson.GCost Saving Potential of Acellular Fish Skin Graft: A Cost Simulation Study on Diabetic Foot Ulcers. 17th Congress of the Asian Society for Vascular Surgery, October 20-23, 2016 Singapore
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DFU Treated with fish skin versus Predictive Model
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Acellular Fish Skin*Standard Care
Lantis J, Magnusson S, Margolis D Baldursson BT, Kjartansson, G Sigurjonsson.G Cost Saving Potential of Acellular Fish Skin Graft: A Cost Simulation Study on Diabetic Foot Ulcers. 17th
Congress of the Asian Society for Vascular Surgery, October 20-23, 2016 Singapore
Reduction in wounds with acellular fish skin* compared to modeled standard of care.
At 20 weeks, 24 of the acellular fish skin graft patients had healed compared to 11 patients with the modeled standard of care group.
27 DFU patients
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ost (
USD
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Acellular Fish Skin*Standard Care
Lantis J, Magnusson S, Margolis D Baldursson BT, Kjartansson, G Sigurjonsson.G Cost Saving Potential of Acellular Fish Skin Graft: A
Cost Simulation Study on Diabetic Foot Ulcers. 17th Congress of the Asian Society for Vascular Surgery, October 20-23, 2016 Singapore
Cost per week at 20 weeks was 28,576 USD for the fish skin* group compared to 93,575 USD for the modeled standard of care group. *ONLY CLOSED PATIENTS ANALYZED
Cost saved with the acellular fish skin graft* per healed wound was 62,5%
Model of Potential Cost SavingsOmega 3 Fish skin* vs Modeled Standard
of Care
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ECM – what and why
Histology – does it matter? Are looks enough?
What we know about composition
Omega 3 fatty acids – what we know so far; balancing inflammation?
Bacterial resistance
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Human dermis Fish dermisSEM pictures show the structure of human and fish dermis in high
magnification. Bar 1µm. Figures:
Regenerative and Antibacterial Properties of Acellular Fish Skin Grafts and Human Amnion/Chorion Membrane: Implications for Tissue Preservation in Combat Casualty Care Skuli Magnusson, BSc*†; Baldur Tumi Baldursson, MD, PhD*‡; Hilmar Kjartansson, MD*‡; Ottar Rolfsson, PhD†; Gudmundur Fertram Sigurjonsson, MEng* MILITARY MEDICINE, 182, 3/4:383, 2017
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Fish Skin and Human Skin Comparison
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Fish Skin Human skin
Regenerative and Antibacterial Properties of Acellular Fish Skin Grafts and Human Amnion/Chorion Membrane: Implications for Tissue Preservation in Combat Casualty Care Skuli Magnusson, BSc*†; Baldur Tumi Baldursson, MD, PhD*‡; Hilmar Kjartansson, MD*‡; Ottar Rolfsson, PhD†; Gudmundur Fertram Sigurjonsson, MEng* MILITARY MEDICINE, 182, 3/4:383, 2017
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The acellular fish skin has been compared to dehydrated human amnion/chorion membrane
(dHACM) allograft, with respect to structure and ability to sustain fibroblast ingrowth in culture
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Fibroblast seeding on Omega3 fish skin graft (left) and a human amnion/chorion membrane allograft (right).
Results show that cells infiltrate and proliferate in the Omega3 Fish graft but not into the human amnion/chorion membrane allograft.
Negative controls showed no cell staining.
Regenerative and Antibacterial Properties of Acellular Fish Skin Grafts and Human Amnion/Chorion Membrane: Implications for Tissue Preservation in Combat Casualty Care Skuli Magnusson, BSc*†; Baldur Tumi Baldursson, MD, PhD*‡; Hilmar Kjartansson, MD*‡; Ottar Rolfsson, PhD†; Gudmundur Fertram Sigurjonsson, MEng* MILITARY MEDICINE, 182, 3/4:383, 2017
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H&E images of cell infiltration into Fish Skin from in vitro experiments
From human implants –showing cell infiltration
Regenerative and Antibacterial Properties of Acellular Fish Skin Grafts and Human Amnion/Chorion Membrane: Implications for Tissue Preservation in Combat Casualty Care Skuli Magnusson, BSc*†; Baldur Tumi Baldursson, MD, PhD*‡; Hilmar Kjartansson, MD*‡; Ottar Rolfsson, PhD†; Gudmundur Fertram Sigurjonsson, MEng* MILITARY MEDICINE, 182, 3/4:383, 2017
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Cellular ingrowth Negative control
Regenerative and Antibacterial Properties of Acellular Fish Skin Grafts and Human Amnion/Chorion Membrane: Implications for Tissue Preservation in Combat Casualty Care Skuli Magnusson, BSc*†; Baldur Tumi Baldursson, MD, PhD*‡; Hilmar Kjartansson, MD*‡; OttarRolfsson, PhD†; Gudmundur Fertram Sigurjonsson, MEng* MILITARY MEDICINE, 182, 3/4:383, 2017
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Inflammation’s role in the chronic woundAnd does adding fatty acids to the wounds work
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http://www.thelancet.com/journals/langas/article/PIIS2468-1253(17)30031-6/fulltext
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Cell signaling for differentiation and migrationEnvironment for tissue regenerationAnti-inflammatory effectsMacrophage switch from M1 to M2Decreased NF-kB and COX expressionBacterial barrierCell membrane integrity
1, Adv Wound Care (New Rochelle). 2014 Nov 1; 3(11): 682–690. doi: 10.1089/wound.2013.0469 PMCID: PMC4217020 Role of Arginine and Omega-3 Fatty Acids in Wound Healing and Infection J. Wesley Alexander1,,2,*and Dorothy M. Supp1 2. Wound Repair Regen. 2008 May-Jun;16(3):337-45. doi: 10.1111/j.1524-475X.2008.00388.x. Omega-3 fatty acids effect on wound healing. McDaniel JC1, Belury M, Ahijevych K, Blakely W
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217020/https://dx.doi.org/10.1089/wound.2013.0469https://www.ncbi.nlm.nih.gov/pubmed/?term=Alexander%20JW%5BAuthor%5D&cauthor=true&cauthor_uid=25371851https://www.ncbi.nlm.nih.gov/pubmed/?term=Supp%20DM%5BAuthor%5D&cauthor=true&cauthor_uid=25371851https://www.ncbi.nlm.nih.gov/pubmed/18471252https://www.ncbi.nlm.nih.gov/pubmed/?term=McDaniel%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=18471252https://www.ncbi.nlm.nih.gov/pubmed/?term=Belury%20M%5BAuthor%5D&cauthor=true&cauthor_uid=18471252https://www.ncbi.nlm.nih.gov/pubmed/?term=Ahijevych%20K%5BAuthor%5D&cauthor=true&cauthor_uid=18471252https://www.ncbi.nlm.nih.gov/pubmed/?term=Blakely%20W%5BAuthor%5D&cauthor=true&cauthor_uid=18471252
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https://www.frontiersin.org/articles/10.3389/fimmu.2017.00071/full
1. Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease. Amaral JJ, Antunes LC, de Macedo CS, Mattos KA, Han J, Pan J, Candéa AL, Henriques Md, Ribeiro-Alves M, BorchersCH, Sarno EN, Bozza PT, Finlay BB, Pessolani MC.PLoS Negl Trop Dis. 2013 Aug 15;7(8 2. Biochem Soc Trans. 2017 Oct 15;45(5):1105-1115. doi: 10.1042/BST20160474. Epub 2017 Sep 12. Omega-3 fatty acids and inflammatory processes: from olecules to man. Calder PC
https://www.ncbi.nlm.nih.gov/pubmed/23967366https://www.ncbi.nlm.nih.gov/pubmed/28900017https://www.ncbi.nlm.nih.gov/pubmed/?term=Calder%20PC%5BAuthor%5D&cauthor=true&cauthor_uid=28900017
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Bone Marrow
concentrate
Whole Bone
MarrowMesenchymal
Stem CellsNegative Control
Fatty acid rich group
Fatty acid rich group
Rodriguez-Menocalet al. Stem Cell Res Ther. 2015; 6(1): 24.
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20% faster healing Wound model with lipid extractSpeeds up the migration of cells in
the wound bed
Lantis J,Magnusson S, Baldursson B, Kjartansson H, Rolfsson O, Sigurjonsson G. Fish skin omega-3 PUFAs induce cell migration and transcription of ALOX15, a specialized pro-resolving mediator forming lipoxygenase. SAWC Fall, October 20-22, 2017, Las Vegas NV
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Omega3 fatty acids activate specialized pro-resolvinpathways
End product is reduction of prostaglandins and less inflammation
Same downstream effects as NSAID drugs
In this study they measured the activation of the pathway with the ALOX-15 gene expression. Lantis J,Magnusson S, Baldursson B, Kjartansson H, Rolfsson O,
Sigurjonsson G. Fish skin omega-3 PUFAs induce cell migration and transcription of ALOX15, a specialized pro-resolving mediator forming lipoxygenase. SAWC Fall, October 20-22, 2017, Las Vegas NV
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Fatty acids
Omega 3 naturally distributed in the skin scaffolding
DHA and EPA types of Omega 3
Low in Omega 6O
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Bovine pericardiumFish SkinHuman SkinAmnion/Chorion
Lantis J,Magnusson S, Baldursson B, Kjartansson H, Rolfsson O, Sigurjonsson G. Fish skin omega-3 PUFAs induce cell migration and transcription of ALOX15, a specialized pro-resolving mediator forming lipoxygenase. SAWC Fall, October 20-22, 2017, Las Vegas NV
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In the two-chamber assay the fish skin graft performed as a bacterial barrier for close to 60 hours compared to 5–45 hours for human amnion/chorion membrane products and several collagen matrix products.
Spiking (>10%) the fish skin with more Omega3 fatty acids enhanced its bacterial barrier function by roughly 80%
Regenerative and Antibacterial Properties of Acellular Fish Skin Grafts and Human Amnion/Chorion Membrane: Implications for Tissue Preservation in Combat Casualty Care Skuli Magnusson, BSc*†; Baldur Tumi Baldursson, MD, PhD*‡; Hilmar Kjartansson, MD*‡; Ottar Rolfsson, PhD†; Gudmundur Fertram Sigurjonsson, MEng* MILITARY MEDICINE, 182, 3/4:383, 2017
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In this model mice were burned for 30 sec with brass blocks to create 3’ burn. The wounds were infected 5 minutes post burn with 400-480x106 of P. mirabilis strain ATCC51393.
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Supportive of use in the OR setting
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Evaluation of Omega-3 Acellular Fish Skin Dermis on Porcine Deep Partial
and Full Thickness Burn Wounds
U.S. Army Institute of Surgical ResearchCombat Trauma and Burn Injuries Research
Randolph Stone II, PhD
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Dr. Christy’s Lab
Office of ResearchAnthony Pusateri, PhDCPT Kottke, PhD
USAISR Veterinary Support BranchComparative Pathology BranchBattlefield Pain Research
Funding SourcesUS Army Medical Research and Materiel CommandOak Ridge Institute for Science and EducationMilitary Burn Research Program
Robert J. Christy, PhDShan Natesan, PhDChristine Kowalczewski, PhDNicholas Clay, PhDRyan Clohessy, PhDNicole Wrice, MSDavid Larson, MSJohn Wall, BSAndrew Kowalczewski, BSKyle Florell, BSSergio Garcia, BSHannah Dillon, BSSean Christy
Burn Injury Research Task Area
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The objective of this project is to evaluate decellularized fish skin graft on deep partial (DPT) and full thickness (FT) burn wounds in a preclinical porcine model.
Evaluate fish skin graft as an acellular dermal matrix and its ability to integrate and improve healing of DPT burn wounds.
Assess fish skin graft use as a temporary dressing prior to grafting and its ability to improve healing of highly meshed autografts on FT burn wounds.
U.S. Army Institute of Surgical ResearchCombat Trauma and Burn Injuries Research, Randolph Stone II, PhD
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Group number Burn Depth (Day -1)
Primary treatment after excision of dead tissue (Day 0) mSTSG Application (Day 7)
2nd Application of Kerecis (Day 7)
1 Full thickness Kerecis Yes (1.5:1) No2 Full thickness Kerecis Yes (3:1) Yes3 Full thickness Cadaver Skin Yes No4 Deep partial thickness Primatrix No No5 Deep partial thickness Kerecis No Yes
6 animals 12 wounds per treatment group
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Images of ModelDay 0 – Post - Debridement
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Kerecis product was easy to apply to wounds and not conducive to bacterial colonization
Kerecis allowed faster re-epithelialization of DPT burn wounds when compared to a commercial comparator (Primatrix)
The quicker re-epithelialization did not result in higher contraction rates as no treatment
Hydration levels correlate with the re-epithelialization with a quicker return to normal skin levels with the Kerecis treatment
Kerecis integrates quicker and a perfused wound bed is obvious at day 14 vs. Primatrix that takes ~21 days to fully integrate
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Upcoming papersLarge cohort of diabetic foot ulcers – Chris Winters, DPMAnalysis / comparison of Fish Skin to multiple other CTPs in a known
military burn animal model
Research needsComprehensive analysis of content – collagen, proteoglycan,
glycosaminoglycan components of Fish Skin
Tissue biopsies of human wounds at one week and one month post implantation – histology
Inflammatory marker analysis in wounds treated with Fish Skin and wounds not treated with Fish skin
Trial of dosing strategy – 2x week then 1 x week, then every other week versus 1x week (aka a leading amniotic)
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A very efficient ECMResistant to bacteriaReadily availableAnti-inflammatory Omega – 3; Potential added pain reductionCan be grafted early at 7 daysIn the OR / BurnResect the wound – apply and skin graft early
In the clinicApply to prep and then close the wound
������Omega 3 Rich Fish Skin:�Treating hard to heal wounds��John C. Lantis II, MD, FACS�Disclosure:Objectives:The When?Setting the Stage for HealingVenous Leg Ulcer Percent Healing Over TimeFirst StepsChoosing the right CTPAdvanced Treatment Strategies for Wounds –�Why?�Why is extracellular matrix (ECM) important? Structural and regulatory role of ECMHow to Choose a CTP to Manage Chronic WoundsThe What?Fish skin – Product overviewCTP Treatment Strategies for Wounds�Extracellular Matrices: A Closer LookClinical Research – The PresentAcute wound healing – � Blinded prospective studies�vs. SIS & dHACMTrial Schedule(s):Results: Fish skin vs SISResults: Fish skin vs dHACMProportional Hazard modelQuestions:Reviews and Prospective series:�All wound typesComplex wound case cohortSlide Number 30Slide Number 31Venous leg ulcersVLU – Prospective cohort studyVLU Prospective cohort studyDiabetic foot ulcersSlide Number 36Slide Number 37Slide Number 384 weeks laterBasic Science: Scanning electron microscopic (SEM) ��Scanning electron microscopic (SEM) �Histology- “It is like human skin”Three Dimensional Cell IngrowthsIn Vitro and In Vivo Histology��Ideal Pore size for early cellular population��Omega 3 Content – “Therefore anti-inflammatory”Balance of inflammationRole of fatty acids and Omega3 –� in tissue repairLipids and inflammationStem cells work significantly worse without their fatty acid environmentPossible translational benefit�Fish skin lipids promotes cell migrationActivates anti inflammatory pathwayFish skin provides Omega 3�Composition with other bioactive moleculesBacterial ResistanceTwo chamber – Staph Aureus ModelMouse Burn Infection Model Pig Burn ModelSlide Number 59AcknowledgementsObjectiveTreatment GroupsSlide Number 63Slide Number 64Slide Number 65Slide Number 66Re-epithelializationH&E - PrimatrixH&E - KerecisH&E - PrimatrixH&E - KerecisSummary of StudyNext steps in researchIn closing