<p><strong>Diabetic foot ulcer</strong> is one of the major complications of <font color="#002bb8000000">the major complications of Diabetes mellitus</font>. It occurs in 15% of all patients with diabetes and precedes 84% of all lower leg <font color="#002bb8">amputations</font>.<sup id="cite_ref-Harold_0-0" class="reference"><font size="2"><font color="#002bb8"><span>[</span>1<span>]</span></font></font></sup>. Major increase in mortality among diabetic patients, observed over the past 20 years is considered to be due to the development of macro and micro vascular complications, including failure of the <font color="#002bb8">wound healing</font> process. <font color="#002bb8">Wound healing</font> is a &lsquo;make-up&rsquo; phenomenon for the portion of tissue that gets destroyed in any open or closed injury to the skin. Being a natural phenomenon, wound healing is usually taken care of by the body&rsquo;s innate mechanism of action that works reliably most of the time. Key feature of <font color="#002bb8">wound healing</font> is stepwise repair of lost <font color="#002bb8">extracellular matrix</font> (ECM) that forms largest component of dermal skin layer.<sup id="cite_ref-Iakovos_1-0" class="reference"><font size="2"><font color="#002bb8"><span>[</span>2<span>]</span></font></font></sup> Therefore controlled and accurate rebuilding becomes essential to avoid under or over healing that may lead to various abnormalities. But in some cases, certain disorders or physiological insult disturbs <font color="#002bb8">wound healing</font> process that otherwise goes very smoothly in an orderly manner. <font color="#002bb8">Diabetes mellitus</font> is one such metabolic disorder that impedes normal steps of wound healing process. Many histopathological studies show prolonged inflammatory phase in diabetic wounds, which causes delay in the formation of mature <font color="#002bb8">granulation tissue</font> and a parallel reduction in <font color="#002bb8">wound</font> <font color="#002bb8">tensile strength</font>.<sup id="cite_ref-McLennan_2-0" class="reference"><font size="2"><font color="#002bb8"><span>[</span>3<span>]</span></font></fontsup></supfont></p><p><font color="#000000">Non-healing chronic diabetic ulcers are often treated with <font color="#002bb8">extracellular matrix</font> replacement therapy. So far, it is a common trend in diabetic foot care domain to use advanced moist wound therapy, bio-engineered tissue or skin substitute, <font color="#002bb8">growth factors</font> and <font color="#002bb8">negative pressure wound therapy</font>.<sup id="cite_ref-Blume_3-0" class="reference"><font size="2"><font color="#002bb8"><span>[</span>4<span>]</span></font></font></sup> No therapy is completely perfect as each type suffers from its own disadvantages. Moist wound therapy is known to promote <font color="#002bb8">fibroblast</font> and <font color="#002bb8">keratinocyte</font> proliferation and migration, collagen synthesis, early <font color="#002bb8">angiogenesis</font> and wound contraction. At present, there are various categories of moist dressings available such as <font color="#002bb8">adhesive</font> backing film, <font color="#002bb8">silicone</font> coated foam, hydrogels, hydrocolloids etc. Unfortunately, all moist dressings cause fluid retention; most of them require secondary dressing and hence are not the best choice for exudative wounds.<sup id="cite_ref-Sharman_4-0" class="reference"><font size="2"><font color="#002bb8"><span>[</span>5<span>]</span></font></font></sup> To address the physiological deficiencies underlying diabetic ulcer, various <font color="#002bb8">tissue engineering</font> technologies have come up with cellular as well as acellular skin replacement products.</p><table id="toc" class="toc"> <tbody> <tr> <td> <div id="toctitle"> <h2>Contents</h2> <span class="toctoggle"><font size="2">[</font><font color="#002bb8" size="2">hide</font><font size="2">]</font></span></divp> <ul> <li class="toclevel-1 tocsection-1"><font color="#002bb8"h2><span classid="tocnumber">1</span> <span class="toctext">Prevention</span></font> </li> <li class="toclevel-1 tocsection-2"><font color="#002bb8"><span class="tocnumber">2</span> <span class="toctext">Risk factors</span></font> </li> <li class="toclevelmw-1 tocsection-3headline"><font color="#002bb8000000"><span class="tocnumber">3</span> <span class="toctext">Pathophysiology</span>Prevention</font> <ul> <li class="toclevel-2 tocsection-4"><font color="#002bb8"><span class="tocnumber">3.1</span> <span class="toctext">Role of Extracellular matrix (ECM) in wound healing</span></font> </lih2> <li class="toclevel-2 tocsection-5"><font color="#002bb8"><span class="tocnumber">3.2</span> <span class="toctext">Altered metabolism</span></font> </li> </ul> </li> <li class="toclevel-1 tocsection-6"p><font color="#002bb8"><span class="tocnumber">4</span> <span class="toctext">Treatment</span></font> </li> <li class="toclevel-1 tocsection-7"><font color="#002bb8"><span class="tocnumber">5</span> <span class="toctext">Future directions</span></font> </li> <li class="toclevel-1 tocsection-8"><font color="#002bb8"><span class="tocnumber">6</span> <span class="toctext">References</span></font> </li> <li class="toclevel-1 tocsection-9"><font color="#002bb8"><span class="tocnumber">7</span> <span class="toctext">See also</span></font> </li> <li class="toclevel-1 tocsection-10"><font color="#002bb8"><span class="tocnumber">8</span> <span class="toctext">External links</span></font> </li> </ul> </td> </tr> </tbody></table><script type="text/javascript">//<![CDATA[if (window.showTocToggle) { var tocShowText = "show"; var tocHideText = "hide"; showTocToggle(); } //]]></script><h2><span id="Prevention" class="mw-headline000000">Prevention</span></h2><p>Prevention is by frequent <font color="#002bb8">chiropody</font> review, good foot hygiene, <font color="#002bb8">diabetic socks</font> and <font color="#002bb8">shoes</font>, and avoiding injury.</font></p>

<li><font color="#000000"><strong>Foot-care education combined with increased surveillance</strong> can reduce the incidence of serious foot lesions <sup id="cite_ref-pmid8498761_5-0" class="reference"><font size="2"><font color="#002bb8"><span>[</span>6<span>]</span></font></fontsup>. </supfont>. </li>

<li><font color="#000000"><strong>Footwear</strong>. </font></li>

<dl><dd><font color="#000000">All major reviews recommend special footwear for patients with a prior ulcer or with foot deformities. One review added neuropathy as an indication for special footwear. The comparison of custom shoes versus well-chosen and well-fitted athletic shoes is not clear. </font></dd></dl><dl><dd>A <font color="#002bb8000000">A meta-analysis</font> by the <font color="#002bb8">Cochrane Collaboration</font> concluded that &quot;there is very limited evidence of the effectiveness of therapeutic shoes&quot; <sup id="cite_ref-pmid10908550_6-0" class="reference"><font size="2"><font color="#002bb8"><span>[</span>7<span>]</span></font></font></sup>. The date of the literature search for this review is not clear. <em>Clinical Evidence</em> reviewed the topic and concluded &quot;Individuals with significant foot deformities should be considered for referral and assessment for customised shoes that can accommodate the altered foot anatomy. In the absence of significant deformities, high quality well fitting non-prescription footwear seems to be a reasonable option&quot; <sup id="cite_ref-pmid16620415_7-0" class="reference"><font size="2"><font color="#002bb8"><span>[</span>8<span>]</span></font></font></sup>. <font color="#002bb8">National Institute for Health and Clinical Excellence</font> has reviewed the topic and concluded that for patients at &quot;high risk of foot ulcers (neuropathy or absent pulses plus deformity or skin changes or previous ulcer&quot; that &quot;specialist footwear and insoles&quot; should be provided <sup id="cite_ref-webNICE_8-0" class="reference"><font size="2"><font color="#002bb8"><span>[</span>9<span>]</span></font></fontsup></supfont> </dd></dl>

<li><a class="external text" rel="nofollow" href="http://diabetic-foot.net" rel="nofollow"><font color="#3366bb">Diabetic Foot Research Page</font></a> at the Southern Arizona Limb Salvage Alliance (SALSA); for Professionals and Patients </li> <li><a class="external text" rel="nofollow" href="http://gentili.net/diabeticfoot/" rel="nofollow"><font color="#3366bb">Imaging of the Diabetic Foot and Its Complications</font></a> </li> <li><a class="external text" rel="nofollow" href="http://diabeticfootonline.blogspot.com/" rel="nofollow"><font color="#3366bb">The Diabetic Foot Blog</font></a> </li> <li><a class="external text" rel="nofollow" href="http://www.podiatrytoday.com/article/5164" rel="nofollow"><font color="#3366bb">Assessing The Potential of Nitric Oxide in the Diabetic Foot</font></a> </li>