Diabetic foot ulcers (DFUs) are one of the most costly and troublesome complications of diabetes mellitus. The wound chronicity of DFUs remains the main challenge in the current and future treatment of this condition. Persistent inflammation results in chronic wounds characterized by dysregulation of immune cells, such as M1 macrophages, and impairs the polarization of M2 macrophages and the subsequent healing process of DFUs. The interactive regulation of M1 and M2 macrophages during DFU healing is critical and seems manageable. This review details how cytokines and signalling pathways are co-ordinately regulated to control the functions of M1 and M2 macrophages in normal wound repair. DFUs are defective in the M1-to-M2 transition, which halts the whole wound-healing machinery. Many pre-clinical and clinical innovative approaches, including the application of topical insulin, CCL chemokines, micro RNAs, stem cells, stem-cell-derived exosomes, skin substitutes, antioxidants, and the most recent Phase III-approved ON101 topical cream, have been shown to modulate the activity of M1 and M2 macrophages in DFUs. ON101, the newest clinically approved product in this setting, is designed specifically to down-regulate M1 macrophages and further modulate the wound microenvironment to favour M2 emergence and expansion. Finally, the recent evolution of macrophage modulation therapies and techniques will improve the effectiveness of the treatment of diverse DFUs.

Diabetic wounds exhibit chronic inflammation and delayed tissue proliferation or remodeling, mainly owing to prolonged proinflammatory (M1) macrophage activity and defects in transition to prohealing/proremodeling (M2a/M2c; CD206⁺ and/or CD163⁺) macrophages. We found that topical treatment with ON101, a plant-based potential therapeutic for diabetic foot ulcers, increased M2c-like (CD163⁺ and CD206⁺) cells and suppressed M1-like cells, altering the inflammatory gene profile in a diabetic mouse model compared with that in the controls. An in vitro macrophage-polarizing model revealed that ON101 directly suppressed CD80⁺ and CD86⁺ M1-macrophage polarization and M1-associated proinflammatory cytokines at both protein and transcriptional levels. Notably, conditioned medium collected from ON101-treated M1 macrophages reversed the M1-conditioned medium‒mediated suppression of CD206⁺ macrophages. Furthermore, conditioned medium from ON101-treated adipocyte progenitor cells significantly promoted CD206⁺ and CD163⁺ macrophages but strongly inhibited M1-like cells. ON101 treatment also stimulated the expression of GCSF and CXCL3 genes in human adipocyte progenitor cells. Interestingly, treatment with recombinant GCSF protein enhanced both CD206⁺ and CD163⁺ M2 markers, whereas CXCL3 treatment only stimulated CD163⁺ M2 macrophages. Depletion of cutaneous M2 macrophages inhibited ON101-induced diabetic wound healing. Thus, ON101 directly suppressed M1 macrophages and facilitated the GCSF- and CXCL3-mediated transition from M1 to M2 macrophages, lowering inflammation and leading to faster diabetic wound healing.

BACKGROUND Glomus tumors are rare benign neurovascular tumors, up to 75% of which occur in the hand, mainly the subungual area. Local recurrence and nail deformity are commonly seen if tumor excision is not performed completely or properly. OBJECTIVE This study was designed to assess the long-term efficacy of microscopic excision of subungual glomus tumors. MATERIALS AND METHODS This retrospective analysis reviewed a total of 22 patients diagnosed with glomus tumors who underwent microscopic surgical excision at a single medical center over a 12-year period (2002–2014). Outcomes were analyzed based on symptom relief, recurrence rate, finger function, nail esthetics, and patient satisfaction. RESULTS With a mean follow-up period of 48.4 months, neither recurrence nor postexcision nail deformity developed in any patient. Patient satisfaction was rated as “good” in 86.3% of patients (19/22). CONCLUSION Microscopic surgical excision enables the surgeon to completely remove a glomus tumor while minimizing damage to the nail unit, thereby resulting in significantly decreased recurrence and nail deformity. In this study, an incision made according to the anatomic location provided an easy approach and the best visualization. Patients' finger function was successfully restored, nail esthetic outcome was good, and patient satisfaction was high.

Reconstruction to close a peripheral nerve gap continues to be a challenge for clinical medicine, and much effort is being made to develop nerve conduits facilitate nerve gap closure. Acellular dermal matrix (ADM) is mainly used to aid wound healing, but its malleability and plasticity potentially enable it to be used in the treatment of nerve gaps. Adipose-derived stem cells (ADSCs) can be differentiated into three germ layer cells, including neurospheres. We tested the ability of ADSC-derived neural stem cells (NSCs) in combination with ADM or acellular sciatic nerve (ASN) to repair a transected sciatic nerve. We found that NSCs form neurospheres that express Nestin and Sox2, and could be co-cultured with ADM in vitro, where they express the survival marker Ki67. Following sciatic nerve transection in rats, treatment with ADM+NSC or ASN+NSC led to increases in relative gastrocnemius weight, cross-sectional muscle fiber area, and sciatic functional index as compared with untreated rats or rats treated with ADM or ASN alone. These findings suggest that ADM combined with NSCs can improve peripheral nerve gap repair after nerve transection and may also be useful for treating other types of neurological gaps.