Diabetic Foot: The Role of Fasciae, a Narrative Review

Abstract

Wound healing is an intricate, dynamic process, in which various elements such as hyperglycemia, neuropathy, blood supply, matrix turnover, wound contraction, and the microbiome all have a role in this “out of tune” diabetic complex symphony, particularly noticeable in the complications of diabetic foot. Recently it was demonstrated that the fasciae have a crucial role in proprioception, muscular force transmission, skin vascularization and tropism, and wound healing. Indeed, the fasciae are a dynamic multifaceted meshwork of connective tissue comprised of diverse cells settled down in the extracellular matrix and nervous fibers; each constituent plays a particular role in the fasciae adapting in various ways to the diverse stimuli. This review intends to deepen the discussion on the possible fascial role in diabetic wounds. In diabetes, the thickening of collagen, the fragmentation of elastic fibers, and the changes in glycosaminoglycans, in particular hyaluronan, leads to changes in the stiffness, gliding, and the distribution of force transmission in the fasciae, with cascading repercussions at the cellular and molecular levels, consequently feeding a vicious pathophysiological circle. A clear scientific perception of fascial role from microscopic and macroscopic points of view can facilitate the identification of appropriate treatment strategies for wounds in diabetes and create new perspectives of treatment.

Age-Related Alterations of Hyaluronan and Collagen in Extracellular Matrix of the Muscle Spindles

“…Daleswski et al [ 22 ] studied the COL5A1 rs12722 and rs13946 polymorphisms as potential genetic factors regulating the ADDwoR-mediated soft tissue pathway in association with temporomandibular joint anterior disc displacement [ 22 ]. Pirri et al [ 46 ] reported that:” excessive aggregation of ECM elements is present in fibrosis (e.g., in myopathies), including in fasciae, and occurs during aging [ 16 ], and diabetes, characterized by increased endomysium as well as perimysium” [ 47 ]. Diet-induced insulin resistance (IR) leads to an increase in the expression of collagens I, III, and IV [ 48 ].…”

Ultrasound examination for a heel scar: seeing/treating the painful superficial fascia

“…Laboratory analyses revealed a microcytic anemia (Hb 118 g/L, MCV 78 fL), leukocytosis (13x109/L) and elevated value of C-reactive protein (45. 6 CM, the most frequent primary tumor in adults, commonly occurs in the left atrium; its occurrence on the valves is extremely rare [1]. The patients may present with 1) symptoms or signs of mechanical outflow tract obstruction in about 60% of the patients, imitating clinical presentation of valve stenosis, 2) general/ constitutional signs and symptoms and laboratory abnormalities in 10-45% of patients and 3) embolization of the tumor fragments or thrombus adherent on the tumor surface in the 30-40% of cases [1].…”

“…In this case, substantial US imaging (including sonopalpation) uncovered the exact pain generator in the subcutaneous tissues including superficial fasciae [1,3]. Accordingly, prompt management was done with in-depth understanding of the symptomatology and tissue biomechanics, as well as targeted intervention whereby reorganization of the subcutaneous tissue caused mechanical stress on the fascial layers, triggering inflammation and stiffness during the healing process [4][5][6].…”

Pathophysiological and Therapeutic Roles of Fascial Hyaluronan in Obesity-Related Myofascial Disease

“…Based on histological properties and anatomical relationships, fascia may be classified into four types: superficial (subcutaneous) fascia, deep/muscular fasciae (aponeurotic and epimysial fasciae), visceral fasciae, and neural fasciae (meningeal layers and connective tissue sheath of peripheral nerves) [ 4 , 5 ]. Structurally the fascia tissue consists of various cell types (fibroblasts, myofibroblasts, fasciacytes, and telocytes), an extracellular matrix consisting of fibrous (types I and III collagen fibers, elastin, and fibrillin), and aqueous (water and complex mixture of glycosaminoglycans) components, and nerve elements (free nerve endings and mechanoreceptors) [ 4 , 6 ].…”

“…Deepening our understanding of the microanatomical and biochemical basis of fascial disease in obesity may provide novel therapeutic insights for the medical and surgical treatment of obesity-related myofascial complications. A significant body of evidence has highlighted the critical role of fascial cells, extracellular matrix, and nerve elements in the pathogenesis of myofascial disease [ 4 , 6 ]. In this regard, a therapeutically relevant consideration is the role of hyaluronan (hyaluronic acid) in clinical fasciopathy.…”