The process is activated, though perhaps not exclusively, by cells responding to fragments of damaged ECM, and the repairs are made by reassembling the matrix by cells growing on and through it. Because of this, extracellular matrix is often considered as a conductor of the wound healing symphony. In the Inflammatory phase, neutrophils and macrophages recruit and activate fibroblasts which in subsequent granulation phase migrate into the wound, laying down new collagen of the subtypes I and III.In the initial events of wound healing, collagen III predominates in the granulation tissue which later on in remodeling phase gets replaced by collagen I giving additional tensile strength to the healing tissue. It is evident from the known collagen assembly that the tensile strength is basically due to fibrillar arrangement of collagen molecules, which self-assemble into microfibrils in a longitudinal as well as lateral manner producing extra strength and stability to the collagen assembly. Metabolically altered collagen is known to be highly inflexible and prone to break down, particularly over pressure areas. Fibronectin is the major glycoprotein secreted by fibroblasts during initial synthesis of extracellular matrix proteins. It serves important functions, being a chemo-attractant for macrophages, fibroblasts and endothelial cells.The basement membrane that separates the epidermis from the dermal layer and the endothelial basement membrane mainly contains collagen IV that forms a sheet and binds to other extracellular matrix molecules like laminin and proteoglycans. In addition to collagen IV, the epidermal and endothelial basement membrane also contains laminin, perlecan and nidogen.
When osteomyelitis is suspected to be involved in the foot ulcer, but not evidenced on an x-ray, an MRI scan should be obtained.With regards to infected foot ulcers, the presence of microorganisms is not in itself enough to determine whether an infection is present. Signs such as inflammation and purulence are the best indicators of an active infection. The most common organism causing infection is staphylococcus. The treatment consists of debridement, appropriate bandages, managing peripheral arterial disease and appropriate use of antibiotics (against pseudomonas aeruginosa, staphylococcus, streptococcus and anaerobe strains), and arterial revascularisation. Fespixon Cream(ON101)
There was a novel topical medication developed by a Taiwanese company, Oneness Biotech Co. Ltd (4743:Taipei), called ON101(officially named Fespixon cream(速必一) later), which showed promising efficacy on diabetic foot ulcer healing. During a 3rd phase clinical trial of 236 patients, it showed superior complete healing rate with 60.7% in 16 weeks in average, comparing to aquacel with 35.1%. Its active components were PA-F4(from Plectranthus amboinicus) and S1(from Centella asiatica).Fespixon Cream(ON101) is a first-in-class macrophage-regulating new drug for the chronic wounds. It can effectively regulate the immune environment in the DFU (hyperglycemia causes dermatological immunopathy on DM patients) by suppressing M1 φ overexpression and increase M2 φ to transit the inflammation stage to proliferation stage and to resolve DFU chronicity. On 2021 February, it was approved by Taiwan Food and Drug Administration to be launched in Taiwan market.