<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">MPS</journal-id><journal-title-group><journal-title>Modern Plastic Surgery</journal-title></journal-title-group><issn pub-type="epub">2164-5213</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/mps.2023.131005</article-id><article-id pub-id-type="publisher-id">MPS-122531</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine&amp;Healthcare</subject></subj-group></article-categories><title-group><article-title>
 
 
  Hypertrophic Scar Formation and Wound Healing Modulation Fatty Acids as Modulators of Severe Scars
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Bárbara</surname><given-names>Díaz</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Valerie</surname><given-names>Nu&amp;#241;ez</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib></contrib-group><aff id="aff1"><addr-line>Department of General Surgery, Burn Unit Care Dr. Ricardo Gutiérrez Children’s Hospital, Buenos Aires, Argentina</addr-line></aff><pub-date pub-type="epub"><day>13</day><month>12</month><year>2022</year></pub-date><volume>13</volume><issue>01</issue><fpage>41</fpage><lpage>51</lpage><history><date date-type="received"><day>1,</day>	<month>November</month>	<year>2022</year></date><date date-type="rev-recd"><day>16,</day>	<month>January</month>	<year>2023</year>	</date><date date-type="accepted"><day>19,</day>	<month>January</month>	<year>2023</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  Scar tissue usually generates severe discomfort in the short and long term. Common symptoms include anesthetics sequelae, pruritus, joint malfunction, new wounds on the scar surface, and pain. There are several treatments for scars, like compression, topical or intralesional steroid infiltration, 5-fluorouracil, dermabrasion, and surgeries with new scar tissue. For adult patients, it is easier to choose the treatment. However, compression is commonly applied in children to prevent treatments that have adverse effects. This study reports the outcomes of 15 patients submitted to abdominoplasty, traumatic wounds and post-burn scar treatments, which showed significant changes after the continuous use of an ointment composed of petrolatum, cod liver oil, BHT, 
  Chamomilla recutita (chamomile) oil, 
  Helianthus annuus (sunflower) oil, and 
  Prunus amygdalus dulcis (sweet almond) oil. As components of the stratum corneum, unsaturated fatty acids influence the cutaneous structural and immune status and permeability. They also interfere with the maturation and differentiation of the stratum corneum and inhibit the production of proinflammatory eicosanoids, reactive species (ROS and RNS), and cytokines, thereby influencing the inflammatory response and possibly wound healing. This article aims to share our experience with the regular use of an ointment in adult and pediatric patients for three months. The increase in proinflammatory cytokine production at wound sites, resulting in a noninvasive, therapeutical, and effective cutaneous wound healing and scarring modulation, may provide a physiopathological explanation for the fast improvement of scars.
 
</p></abstract><kwd-group><kwd>Scarring</kwd><kwd> Burn Scar</kwd><kwd> Inflammatory Modulation</kwd><kwd> Cytokine</kwd><kwd> Sequelae</kwd><kwd> Fatty Acids</kwd><kwd> Eicosanoids</kwd><kwd> Non-Adverse Effects</kwd><kwd> Aesthetics</kwd><kwd> Hypertrophic</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>Burn surgeons observe daily that, immediately after the acute treatment, burn patients experience an undetermined evolution stage. That stage is challenging to manage, as it requires long rehabilitation times, particularly in flexion-extension areas, and surgical revisions.</p><p>In developing countries, scar treatment is usually challenging due to long distances to specialized centers, treatment costs, difficult access to medical technology, and insufficient recognition of these pathologies by the public health systems.</p><p>In Latin America and our practice, phototypes IV to VI of the Fitzpatrick scale are prevalent as brown skin tends to scar pigmentation and has a greater risk of forming hypertrophic or keloid scars [<xref ref-type="bibr" rid="scirp.122531-ref1">1</xref>] [<xref ref-type="bibr" rid="scirp.122531-ref2">2</xref>].</p><p>In cosmetic surgery, hypertrophic scars and keloids pose an aesthetic and functional problem. One study found that 60% of the patients were unsatisfied with the cosmetic results of their scars after dermatologic and cosmetic surgery procedures, and up to 90% wanted to improve their appearance [<xref ref-type="bibr" rid="scirp.122531-ref3">3</xref>].</p><p>Curefini was initially, and it is currently used as a topical treatment for epidermolysis bullosa and chronic wound healing. No adverse effects and good wound-healing outcomes have been reported. Our team has a long experience in surgical treatments, and we started using the product to treat small, ulcerated lesions that remain in the final stage of burn healing. We observed that healed areas improved faster, showing more elasticity, better texture, less itching, and reduced post-inflammatory vascularity and pigmentation.</p><p>Therefore, planning scars is just as important as planning flaps. An efficient topical medication, combined with usual therapies, may aid the modulation of healing stages.</p></sec><sec id="s2"><title>2. Objectives</title><p>This article aims to demonstrate that the use of Curefini<sup>&#174;</sup>, associated with traditional scar modulation therapies, is more efficient in producing better scar cosmetic and functional outcomes than only moisturizing creams associated with those treatments.</p><p>The evaluated treatment complied with the specifications for the clinical use of the drugs. In this regard, all clinical research should safeguard the dignity of participating subjects, ensuring their rights, particularly their autonomy and physical, mental, and oral integrity. [<xref ref-type="bibr" rid="scirp.122531-ref4">4</xref>]</p></sec><sec id="s3"><title>3. Material and Methods</title><p>This study included 15 patients under acute stage resolution, treated or not with grafts, presenting hypertrophic scars with erythema or pigmented scars up to six months from the start of healing.</p><p>Patients with scars older than two years and stable were excluded because they presented no measurable differences suitable for this study, keloid scars that could not be partially resected or submitted to z-plasty, or keloids requiring immunomodulatory treatment.</p><p>Both adult patients and pediatric patient surrogates granted their consent to participate in this study, per the ethical-legal regulations.</p><p>The topical medication used was Curefini<sup>&#174;</sup>, an ointment composed of sunflower oil, cod liver oil, beeswax, sweet almond oil, petroleum jelly (Vaseline<sup>&#174;</sup>), and butylated hydroxytoluene (BHT). [<xref ref-type="bibr" rid="scirp.122531-ref5">5</xref>]</p><p>The protocol was applied for three months. Curefini<sup>&#174;</sup> was applied to hypertrophic scars resulting from burns or cosmetic surgeries. Photographic records were made at 30, 60, and 90 days of treatment to evaluate scar evolution in terms of scar pigmentation, itching reduction, and elasticity improvement. The Vancouver Scar Scale [<xref ref-type="bibr" rid="scirp.122531-ref6">6</xref>] [<xref ref-type="bibr" rid="scirp.122531-ref7">7</xref>] [<xref ref-type="bibr" rid="scirp.122531-ref8">8</xref>] (<xref ref-type="table" rid="table1">Table 1</xref>) and photographic records of the parameters specified in the protocol were used as a reference for scar evolution.</p><table-wrap id="table1" ><label><xref ref-type="table" rid="table1">Table 1</xref></label><caption><title> Vancouver scar scale</title></caption><table><tbody><thead><tr><th align="center" valign="middle"  colspan="2"  >Scar characteristic</th></tr></thead><tr><td align="center" valign="middle" >Vascularity</td><td align="center" valign="middle" >Score</td></tr><tr><td align="center" valign="middle" >Normal</td><td align="center" valign="middle" >0</td></tr><tr><td align="center" valign="middle" >Pink</td><td align="center" valign="middle" >1</td></tr><tr><td align="center" valign="middle" >Red</td><td align="center" valign="middle" >2</td></tr><tr><td align="center" valign="middle" >Purple</td><td align="center" valign="middle" >3</td></tr><tr><td align="center" valign="middle" >Pigmentation</td><td align="center" valign="middle" ></td></tr><tr><td align="center" valign="middle" >Normal</td><td align="center" valign="middle" >0</td></tr><tr><td align="center" valign="middle" >Hypopigmentation</td><td align="center" valign="middle" >1</td></tr><tr><td align="center" valign="middle" >Hyperpigmentation</td><td align="center" valign="middle" >2</td></tr><tr><td align="center" valign="middle" >Pliability</td><td align="center" valign="middle" ></td></tr><tr><td align="center" valign="middle" >Normal</td><td align="center" valign="middle" >0</td></tr><tr><td align="center" valign="middle" >Supple</td><td align="center" valign="middle" >1</td></tr><tr><td align="center" valign="middle" >Yielding</td><td align="center" valign="middle" >2</td></tr><tr><td align="center" valign="middle" >Firm</td><td align="center" valign="middle" >3</td></tr><tr><td align="center" valign="middle" >Ropes</td><td align="center" valign="middle" >4</td></tr><tr><td align="center" valign="middle" >Contracture</td><td align="center" valign="middle" >5</td></tr><tr><td align="center" valign="middle" >Height (mm)</td><td align="center" valign="middle" ></td></tr><tr><td align="center" valign="middle" >Flat</td><td align="center" valign="middle" >0</td></tr><tr><td align="center" valign="middle" >&lt;2</td><td align="center" valign="middle" >1</td></tr><tr><td align="center" valign="middle" >2 - 5</td><td align="center" valign="middle" >2</td></tr><tr><td align="center" valign="middle" >&gt;5</td><td align="center" valign="middle" >3</td></tr><tr><td align="center" valign="middle" >Total score</td><td align="center" valign="middle" >13</td></tr></tbody></table></table-wrap><p>Despite being a subjective clinical assessment tool designed to describe scars in general—not hypertrophic scars—we chose the Vancouver Scar Scale in this study because it is simple, easy to apply in low-technology settings, and possibly the most recognized burn scar assessment method. The VSS remains widely applicable to evaluate therapy and as a measure of outcome in burn studies. [<xref ref-type="bibr" rid="scirp.122531-ref9">9</xref>]</p><sec id="s3_1"><title>3.1. Pathophysiology of Healing and Role of Polyunsaturated Fatty Acids</title><p>Pathological scars are caused by an excessive response to the activity of TGF-β1. Connective tissue growth factors are overexpressed 100- to 150-fold in hypertrophic and keloid scars, respectively, in response to this cytokine compared with normal fibroblasts. [<xref ref-type="bibr" rid="scirp.122531-ref10">10</xref>] [<xref ref-type="bibr" rid="scirp.122531-ref11">11</xref>]</p><p>Our treatment was based on studies that showed that the concentration of polyunsaturated fatty acids (PUFA, EPA, DHA) influences the synthesis and activity of proinflammatory cytokines and inhibits the expression of the gene induced by TGF-β1, inhibiting pro-fibrogenesis. [<xref ref-type="bibr" rid="scirp.122531-ref12">12</xref>] [<xref ref-type="bibr" rid="scirp.122531-ref13">13</xref>]</p><p>Those fatty acids may partially inhibit some inflammation processes, such as leukocyte chemotaxis, adhesion expression molecules and leukocyte interactions with the endothelium, the production of eicosanoids, such as prostaglandins and leukotrienes, from arachidonic n-6 PUFA, and T-cell inflammatory cytokine production and reactivity. Eicosapentaenoic acid (EPA) stimulates the biological activity of arachidonic acid (AA) derivatives and the synthesis of active mediators of inflammation resolution, such as resolvins and protectins. [<xref ref-type="bibr" rid="scirp.122531-ref14">14</xref>]</p><p>Those mediators compete with cyclooxygenases and lipoxygenases and reduce the expression of COX-2 and 5-lipoxygenase, with a beneficial anti-inflammatory effect of n-3 PUFAs. [<xref ref-type="bibr" rid="scirp.122531-ref15">15</xref>] [<xref ref-type="bibr" rid="scirp.122531-ref16">16</xref>]</p></sec><sec id="s3_2"><title>3.2. The Role of Vitamin D in Inflammation</title><p>Supplied by sunflower, sweet almond oil, and cod liver oil, vitamin D significantly reduces IL-6 and TNF-α levels. Using cholecalciferol receptors, it directly binds to leukocyte DNA, activating the MKP-1 gene and thereby interfering in the inflammatory cascade. [<xref ref-type="bibr" rid="scirp.122531-ref17">17</xref>] [<xref ref-type="bibr" rid="scirp.122531-ref18">18</xref>]</p></sec><sec id="s3_3"><title>3.3. Virgin Beeswax</title><p>It contains long-chain polysaccharides, long-chain free fatty acids, palmitic acid, and exogenous compounds. It is associated with other components as a skin protector, as it is highly hydrophobic. Studies carried out in 2016 report that it has antibacterial activity against S. aureus and antifungal activity against C. albicans. [<xref ref-type="bibr" rid="scirp.122531-ref5">5</xref>]</p></sec><sec id="s3_4"><title>3.4. Study Description</title><p>Our experience with Curefini<sup>&#174;</sup> in the combined treatment for burn sequelae began in 2019.</p><p>Our “patient 0” was an adolescent female admitted on 08/20/2019 due to an extensive burn by direct fire. She remained hospitalized for a long time due to Pseudomonas A infection acquired in the hospital. She was submitted to grafting and discharged on 10/25/2019 (<xref ref-type="fig" rid="fig1">Figure 1</xref>). On 03/12/2020, she started elastic bandage compression and Curefini<sup>&#174;</sup> treatment (<xref ref-type="fig" rid="fig2">Figure 2</xref>).</p><p>The patient discontinued compressive treatment three months after the start and revisited the hospital on 04/19/2021, showing an elastic, hypopigmented scar with some hypertrophic nuclei under regression (<xref ref-type="fig" rid="fig3">Figure 3</xref>).</p><p>The patient was maintained under the ointment treatment only.</p><p>We then decided to apply an evaluation protocol of the topical treatment without interrupting the usual therapies.</p></sec></sec><sec id="s4"><title>4. Results</title><p>Healing is an active process that lasts 12 - 18 months.</p><p>Although between the first 15 to 30 days the patients without compressive treatment showed an increase in purplish-red scar pigmentation, after 90 days the scars showed less erythema due to a decrease in the vascular scar component.</p><p>A notable decrease was observed in the Vancouver Scar Scale score in the treated patients during that period. (<xref ref-type="table" rid="table2">Table 2</xref>)</p><p>Although some scars initially showed severe pliability scores, the firmness, pigmentation, itching, and superficial lesions commonly observed in hypertrophic scars were reduced.</p><p>Patients who started topical treatment with Curefini<sup>&#174;</sup> and required surgical treatment (surgical skin flaps, z-plasty, new grafts) showed better post-surgical healing of the new scars.</p><p>One of the adult patients presented wound dehiscence due to infection with Staphylococcus A (MRSA) and was submitted to surgical debridement and secondary intention wound healing, showing a rapid regression of the initial surgical wound.</p><p>It was not possible to evaluate one of the abdominoplasties at 60 days, but at 90 days post-surgery, the wound already had the characteristics of a mature scar.</p><p>Only one patient showed no changes between 60 to 90 days, but at 120 days, the wound remained stable.</p><p>No patient presented any irritation, pruritus, or allergy signs to the ointment used.</p>Photographic Record<p>Wound evolution between 30 and 90 days is shown below. Due to the vast number of records, only the most significant are shown. (Figures 4-18)</p><table-wrap id="table2" ><label><xref ref-type="table" rid="table2">Table 2</xref></label><caption><title> Vancouver scar scale results</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Patient</th><th align="center" valign="middle" >Age (yrs.)</th><th align="center" valign="middle" >Start treat.</th><th align="center" valign="middle" >30 D</th><th align="center" valign="middle" >60 D</th><th align="center" valign="middle" >90 D</th><th align="center" valign="middle" >Scar</th><th align="center" valign="middle" >Compression</th><th align="center" valign="middle" >Graft</th></tr></thead><tr><td align="center" valign="middle" >AL</td><td align="center" valign="middle" >46</td><td align="center" valign="middle" >6</td><td align="center" valign="middle" >2</td><td align="center" valign="middle" >0</td><td align="center" valign="middle" >0</td><td align="center" valign="middle" >Abdominoplasty</td><td align="center" valign="middle" >No</td><td align="center" valign="middle" >No</td></tr><tr><td align="center" valign="middle" >SS</td><td align="center" valign="middle" >43</td><td align="center" valign="middle" >9</td><td align="center" valign="middle" >10</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >2</td><td align="center" valign="middle" >Abdominoplasty</td><td align="center" valign="middle" >No</td><td align="center" valign="middle" >No</td></tr><tr><td align="center" valign="middle" >FA</td><td align="center" valign="middle" >49</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >0</td><td align="center" valign="middle" >Abdominoplasty</td><td align="center" valign="middle" >No</td><td align="center" valign="middle" >No</td></tr><tr><td align="center" valign="middle" >ID</td><td align="center" valign="middle" >2</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >6</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >3</td><td align="center" valign="middle" >Ant. Thorax burn</td><td align="center" valign="middle" >Yes</td><td align="center" valign="middle" >No</td></tr><tr><td align="center" valign="middle" >MM</td><td align="center" valign="middle" >10</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >7</td><td align="center" valign="middle" >7</td><td align="center" valign="middle" >Abdomen burn</td><td align="center" valign="middle" >Yes</td><td align="center" valign="middle" >No</td></tr><tr><td align="center" valign="middle" >CM</td><td align="center" valign="middle" >2</td><td align="center" valign="middle" >12</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >6</td><td align="center" valign="middle" >6</td><td align="center" valign="middle" >Neck burn</td><td align="center" valign="middle" >No</td><td align="center" valign="middle" >Yes</td></tr><tr><td align="center" valign="middle" >AL</td><td align="center" valign="middle" >18</td><td align="center" valign="middle" >12</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >6</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >Neck burn</td><td align="center" valign="middle" >No</td><td align="center" valign="middle" >Yes</td></tr><tr><td align="center" valign="middle" >FJ</td><td align="center" valign="middle" >6</td><td align="center" valign="middle" >13</td><td align="center" valign="middle" >11</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >Hand burn</td><td align="center" valign="middle" >Yes</td><td align="center" valign="middle" >Yes</td></tr><tr><td align="center" valign="middle" >CS</td><td align="center" valign="middle" >12</td><td align="center" valign="middle" >7</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >Hand burn</td><td align="center" valign="middle" >No</td><td align="center" valign="middle" >No</td></tr><tr><td align="center" valign="middle" >SV</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >9</td><td align="center" valign="middle" >7</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >3</td><td align="center" valign="middle" >Forearm burn</td><td align="center" valign="middle" >Yes</td><td align="center" valign="middle" >Yes</td></tr><tr><td align="center" valign="middle" >FA</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >12</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >6</td><td align="center" valign="middle" >6</td><td align="center" valign="middle" >Ankle burn</td><td align="center" valign="middle" >No</td><td align="center" valign="middle" >Yes</td></tr><tr><td align="center" valign="middle" >LB</td><td align="center" valign="middle" >16</td><td align="center" valign="middle" >9</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >?</td><td align="center" valign="middle" >Foot burn</td><td align="center" valign="middle" >No</td><td align="center" valign="middle" >Yes</td></tr><tr><td align="center" valign="middle" >MO</td><td align="center" valign="middle" >20</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >1</td><td align="center" valign="middle" >0</td><td align="center" valign="middle" >0</td><td align="center" valign="middle" >Ciliary burn</td><td align="center" valign="middle" >No</td><td align="center" valign="middle" >No</td></tr><tr><td align="center" valign="middle" >SM</td><td align="center" valign="middle" >45</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >3</td><td align="center" valign="middle" >2</td><td align="center" valign="middle" >0</td><td align="center" valign="middle" >Lower eyelid tumor</td><td align="center" valign="middle" >No</td><td align="center" valign="middle" >Yes</td></tr><tr><td align="center" valign="middle" >PS</td><td align="center" valign="middle" >82</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >2</td><td align="center" valign="middle" >0</td><td align="center" valign="middle" >Lower limb wound</td><td align="center" valign="middle" >No</td><td align="center" valign="middle" >No</td></tr></tbody></table></table-wrap></sec><sec id="s5"><title>5. Conclusions</title><p>Using a topical treatment with minimal risk of adverse effects as a complementary therapy to inhibit chronic inflammation significantly reduces the number and complexity of scar revision surgeries, provides better comfort for patients requiring compressive dressings, and produces more elastic and less visible scars in a shorter time.</p><p>Based on our experience, surgery planning may be now different, as the use of Curefini<sup>&#174;</sup> before surgery allowed for obtaining more elastic scars and planning flaps with the same grafted skin as the new scars are easier to conceal.</p><p>In cosmetic surgery, the use of Curefini<sup>&#174;</sup> immediately post-op shortens healing time and provides satisfying scar results.</p></sec><sec id="s6"><title>Conflicts of Interest</title><p>The authors declare no conflicts of interest regarding the publication of this paper.</p></sec><sec id="s7"><title>Cite this paper</title><p>D&#237;az, B. and Nu&#241;ez, V. (2023) Hypertrophic Scar Formation and Wound Healing Modulation Fatty Acids as Modulators of Severe Scars. Modern Plastic Surgery, 13, 41-51. https://doi.org/10.4236/mps.2023.131005</p></sec></body><back><ref-list><title>References</title><ref id="scirp.122531-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Berardesca, E. and Maibach, H. (1996) Racial Differences in Skin Pathology. Journal of the American Academy of Dermatology, 34, 667-672. https://doi.org/10.1016/S0190-9622(96)80070-3</mixed-citation></ref><ref id="scirp.122531-ref2"><label>2</label><mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Ribera</surname><given-names> N.M. </given-names></name>,<etal>et al</etal>. 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