Validation of multispectral imaging-based tissue oxygen saturation detecting system for wound healing recognition on open wounds.

Significance: The multispectral imaging-based tissue oxygen saturation detecting (TOSD) system offers deeper penetration ( ∼ 2 to 3 mm) and comprehensive tissue oxygen saturation ( StO 2 ) assessment and recognizes the wound healing phase at a low cost and computational requirement. The potential for miniaturization and integration of TOSD into telemedicine platforms could revolutionize wound care in the challenging pandemic era. Aim: We aim to validate TOSD's application in detecting StO 2 by comparing it with wound closure rates and laser speckle contrast imaging (LSCI), demonstrating TOSD's ability to recognize the wound healing process. Approach: Utilizing a murine model, we compared TOSD with digital photography and LSCI for comprehensive wound observation in five mice with 6-mm back wounds. Sequential biochemical analysis of wound discharge was investigated for the translational relevance of TOSD. Results: TOSD demonstrated constant signals on unwounded skin with differential changes on open wounds. Compared with LSCI, TOSD provides indicative recognition of the proliferative phase during wound healing, with a higher correlation coefficient to wound closure rate (TOSD: 0.58; LSCI: 0.44). StO 2 detected by TOSD was further correlated with proliferative phase angiogenesis markers. Conclusions: Our findings suggest TOSD's enhanced utility in wound management protocols, evaluating clinical staging and therapeutic outcomes. By offering a noncontact, convenient monitoring tool, TOSD can be applied to telemedicine, aiming to advance wound care and regeneration, potentially improving patient outcomes and reducing healthcare costs associated with chronic wounds.

Profibrotic Subsets of SPP1+ Macrophages and POSTN+ Fibroblasts Contribute to Fibrotic Scarring in Acne Keloidalis.

Acne keloidalis is a primary scarring alopecia characterized by longstanding inflammation in the scalp causing keloid-like scar formation and hair loss. Histologically, acne keloidalis is characterized by mixed leukocytic infiltrates in the acute stage followed by a granulomatous reaction and extensive fibrosis in the later stages. To further explore its pathogenesis, bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics were applied to occipital scalp biopsy specimens of lesional and adjacent no-lesional skin in patients with clinically active disease. Unbiased clustering revealed 19 distinct cell populations, including 2 notable populations: POSTN+ fibroblasts with enriched extracellular matrix signatures and SPP1+ myeloid cells with an M2 macrophage phenotype. Cell communication analyses indicated that fibroblasts and myeloid cells communicated by SPP1 signaling networks in lesional skin. A reverse transcriptomics in silico approach identified corticosteroids as possessing the capability to reverse the gene expression signatures of SPP1+ myeloid cells and POSTN+ fibroblasts. Intralesional corticosteroid injection greatly reduced SPP1 and POSTN gene expression as well as acne keloidalis disease activity. Spatial transcriptomics and immunofluorescence staining verified microanatomic specificity of SPP1+ myeloid cells and POSTN+ fibroblasts with disease activity. In summary, the communication between POSTN+ fibroblasts and SPP1+ myeloid cells by SPP1 axis may contribute to the pathogenesis of acne keloidalis.

TEM1/endosialin/CD248 promotes pathologic scarring and TGF-ß activity through its receptor stability in dermal fibroblasts.

BACKGROUND: Pathologic scars, including keloids and hypertrophic scars, represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. Additionally, the pathobiology of pathologic scars remains poorly understood. We aim at investigating the impact of TEM1 (also known as endosialin or CD248), which is a glycosylated type I transmembrane protein, on development of pathologic scars. METHODS: To investigate the expression of TEM1, we utilized immunofluorescence staining, Western blotting, and single-cell RNA-sequencing (scRNA-seq) techniques. We conducted in vitro cell culture experiments and an in vivo stretch-induced scar mouse model to study the involvement of TEM1 in TGF-ß-mediated responses in pathologic scars. RESULTS: The levels of the protein TEM1 are elevated in both hypertrophic scars and keloids in comparison to normal skin. A re-analysis of scRNA-seq datasets reveals that a major profibrotic subpopulation of keloid and hypertrophic scar fibroblasts greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, and ECM production in human dermal fibroblasts by enhancing TGF-ß1 signaling through binding with and stabilizing TGF-ß receptors. Global deletion of Tem1 markedly reduces the amount of ECM synthesis and inflammation in a scar in a mouse model of stretch-induced pathologic scarring. The intralesional administration of ontuxizumab, a humanized IgG monoclonal antibody targeting TEM1, significantly decreased both the size and collagen density of keloids. CONCLUSIONS: Our data indicate that TEM1 plays a role in pathologic scarring, with its synergistic effect on the TGF-ß signaling contributing to dermal fibroblast activation. Targeting TEM1 may represent a novel therapeutic approach in reducing the morbidity of pathologic scars.