visual impairment) are further risk factors for diabetic foot ulcer.People with diabetes often develop diabetic neuropathy due to several metabolic and neurovascular factors. Peripheral neuropathy causes loss of pain or feeling in the toes, feet, legs, and arms due to distal nerve damage and low blood flow. Autonomic neuropathy causes Sudomotor dysfunction and dryness of the skin. Blisters and sores may appear on numb areas of the feet and legs, such as metatarsophalangeal joints and the heel region, as a result of pressure or injury which may go unnoticed and eventually become a portal of entry for bacteria and infection. Pathophysiology
Extracellular matrix
Extra cellular matrix (or "ECM") is the external structural framework that cells attach to in multicellular organisms. The dermis lies below the epidermis, and these two layers are collectively known as the skin. Dermal skin is primarily a combination of fibroblasts growing in this matrix. The specific species of ECM of connective tissues often differ chemically, but collagen generally forms the bulk of the structure.Through the interaction of a cell with its extracellular matrix (transmitted through the anchoring molecules classed as integrins) there forms a continuous association between the cell interior, cell membrane and its extracellular matrix components that helps drive various cellular events in a regulated fashion. Wound healing is a localized event involving the reaction of cells to the damage sustained.The cells break down damaged ECM and replace it, generally increasing in number to react to the harm.
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.