Melanoma represents the most aggressive and the deadliest form of skin cancer. Current therapeutic approaches include surgical resection, chemotherapy, photodynamic therapy, immunotherapy, biochemotherapy, and targeted therapy. The therapeutic strategy can include single agents or combined therapies, depending on the patient’s health, stage, and location of the tumor. The efficiency of these treatments can be decreased due to the development of diverse resistance mechanisms. New therapeutic targets have emerged from studies of the genetic profile of melanocytes and from the identification of molecular factors involved in the pathogenesis of the malignant transformation. In this review, we aim to survey therapies approved and under evaluation for melanoma treatment and relevant research on the molecular mechanisms underlying melanomagenesis.

Extracellular matrix (ECM)-based bioinks have been steadily gaining interest in the field of bioprinting to develop biologically relevant and functional tissue constructs. Herein, we propose the use of supercritical carbon dioxide (scCO₂) technology to extract the ECM components of cell-sheets that have shown promising results in creating accurate 3D microenvironments replicating the cell’s own ECM, to be used in the preparation of bioinks. The ECM extraction protocol best fitted for cell sheets was defined by considering efficient DNA removal with a minor effect on the ECM. Cell sheets of human dermal fibroblasts (hDFbs) and adipose stem cells (hASCs) were processed using a customised supercritical system by varying the pressure of the reactor, presence, exposure time, and type of co-solvent. A quantification of the amount of DNA, protein, and sulfated glycosaminoglycans (sGAGs) was carried out to determine the efficiency of the extraction in relation to standard decellularization methodologies. The bioinks containing the extracted ECM were fabricated by combining them with alginate as a support polymer. The influence of the alginate (1%, 2% w/vol) and ECM (0.5% and 1.5% w/vol) amounts on the printability of the blends was addressed by analysing the rheological behaviour of the suspensions. Finally, 3D printed constructs were fabricated using an in-house built extrusion-based bioprinter, and the impact of the extrusion process on cell viability was assessed. The optimised scCO₂ protocol allowed efficient removal of DNA while preserving a higher number of proteins and sGAGs than the standard methodologies. The characterization of extract’s composition also revealed that the ECM produced by hDFbs (fECM) and hASCs (aECM) is distinctively affected by the extraction protocols. Furthermore, rheological analysis indicated an increase in viscosity with increasing ECM composition, an effect even more prominent in samples containing aECM. 3D printing of alginate/ECM constructs demonstrated that cell viability was only marginally affected by the extrusion process, and this effect was also dependent on the ECM source. Overall, this work highlights the benefits of supercritical fluid-based methods for ECM extraction and strengthens the relevance of ECM-derived bioinks in the development of printed tissue-like constructs.

Background: Musculoskeletal (MSK) disorders are leading causes of disability worldwide, with clinical guidelines recommending physical therapy–based interventions. Digital MSK programs offer an alternative to address logistical and socioeconomic barriers to regular in-person care. However, evidence comparing surgical use between digital and in-person physical therapy remains limited, particularly for low-value procedures. Objective: This study aimed to evaluate the 12-month incidence of MSK surgery and low-value surgical procedures among participants initiating a multimodal Digital Care Program (DCP) versus a matched-cohort initiating in-person physical therapy. Methods: Retrospective, matched-cohort study, using exact and propensity matching, with a Health Insurance Portability and Accountability Act (HIPAA)–deidentified US nationwide merged claims dataset (July 2022-February 2025). Eligible adults had spine, knee, hip, or shoulder conditions, ≥24 months uninterrupted health insurance coverage to an employer-sponsored DCP, and no MSK surgery in the prior year. The intervention group (IG) participated in a DCP combining exercise, education, and cognitive behavioral therapy, with real-time biofeedback and remote physical therapist oversight. The comparator group (CG) initiated in-person physical therapy, identified from a third-party claims database, using relevant MSK ICD-10 (International Statistical Classification of Diseases, Tenth Revision) codes as primary diagnosis. The primary outcome was the incidence of any MSK surgery within 12 months; the secondary outcome was the incidence of low-value surgery based on Choosing Wisely–aligned definitions. Cohort characteristics were compared using t test and chi-square test. Risk ratios (RRs) were calculated overall and by pain site, age group, and Social Deprivation Index. Results: In a matched cohort of 4190 individuals, predominantly middle-aged (~52 years old) women (1335/2095, 63.7%) with spinal pain (1123/2095, 53.6%), participation in the digital program was linked to a 58% (95% CI 49-66) lower relative risk of surgery at 12 months compared to those initiating in-person physical therapy (RR 0.42, 95% CI 0.34-0.52; E-value=4.19 [lower CI 3.29]). For surgeries categorized as low-value, IG was associated with 82% (95% CI 68-90) lower relative risk (RR 0.17, 95% CI 0.09-0.31; E-value=11.24 [lower CI 5.91]). Overall MSK surgical trends were consistent across pain sites, with greatest relative differences for knee (IG: 40/414 9.7% vs CG: 122/414, 29.5%; RR 0.26; 95% CI 0.17-0.38) followed by hip (19/203, 9.4% vs 42/203, 20.7%; RR 0.40; 95% CI 0.22-0.71). Lower surgery incidences in the IG (overall and low-value) were found across all socioeconomic and age strata. Conclusions: This real-world study demonstrated, for the first time, that participation in a digital MSK program was associated with substantially lower incidences of both overall and low-value surgeries compared to those who opted for in-person physical therapy among commercially-insured adults. These findings suggest that digital MSK programs can mitigate access barriers, promote adherence to guideline-concordant care, and reduce unnecessary procedures, including among underserved populations.

Women’s health is an underserved dimension of public health [1–3], resulting in women spending ∼25% more of their lives in poor health compared to men [1]. Pelvic floor dysfunction (PFD), such as u...

BACKGROUND Musculoskeletal (MSK) disorders are leading causes of disability worldwide, with clinical guidelines recommending physical therapy–based interventions. Digital MSK programs offer an alternative to address logistical and socioeconomic barriers to regular in-person care. However, evidence comparing surgical use between digital and in-person physical therapy remains limited, particularly for low-value procedures. OBJECTIVE This study aimed to evaluate the 12-month incidence of MSK surgery and low-value surgical procedures among participants initiating a multimodal Digital Care Program (DCP) versus a matched-cohort initiating in-person physical therapy. METHODS Retrospective, matched-cohort study, using exact and propensity matching, with a Health Insurance Portability and Accountability Act (HIPAA)–deidentified US nationwide merged claims dataset (July 2022-February 2025). Eligible adults had spine, knee, hip, or shoulder conditions, ≥24 months uninterrupted health insurance coverage to an employer-sponsored DCP, and no MSK surgery in the prior year. The intervention group (IG) participated in a DCP combining exercise, education, and cognitive behavioral therapy, with real-time biofeedback and remote physical therapist oversight. The comparator group (CG) initiated in-person physical therapy, identified from a third-party claims database, using relevant MSK ICD-10 (International Statistical Classification of Diseases, Tenth Revision) codes as primary diagnosis. The primary outcome was the incidence of any MSK surgery within 12 months; the secondary outcome was the incidence of low-value surgery based on Choosing Wisely–aligned definitions. Cohort characteristics were compared using t test and chi-square test. Risk ratios (RRs) were calculated overall and by pain site, age group, and Social Deprivation Index. RESULTS In a matched cohort of 4190 individuals, predominantly middle-aged (~52 years old) women (1335/2095, 63.7%) with spinal pain (1123/2095, 53.6%), participation in the digital program was linked to a 58% (95% CI 49-66) lower relative risk of surgery at 12 months compared to those initiating in-person physical therapy (RR 0.42, 95% CI 0.34-0.52; E-value=4.19 [lower CI 3.29]). For surgeries categorized as low-value, IG was associated with 82% (95% CI 68-90) lower relative risk (RR 0.17, 95% CI 0.09-0.31; E-value=11.24 [lower CI 5.91]). Overall MSK surgical trends were consistent across pain sites, with greatest relative differences for knee (IG: 40/414 9.7% vs CG: 122/414, 29.5%; RR 0.26; 95% CI 0.17-0.38) followed by hip (19/203, 9.4% vs 42/203, 20.7%; RR 0.40; 95% CI 0.22-0.71). Lower surgery incidences in the IG (overall and low-value) were found across all socioeconomic and age strata. CONCLUSIONS This real-world study demonstrated, for the first time, that participation in a digital MSK program was associated with substantially lower incidences of both overall and low-value surgeries compared to those who opted for in-person physical therapy among commercially-insured adults. These findings suggest that digital MSK programs can mitigate access barriers, promote adherence to guideline-concordant care, and reduce unnecessary procedures, including among underserved populations.