Obesity is a risk factor for total knee arthroplasty (TKA). Wound dehiscence and surgical site infections (SSIs) are the main complications of TKA in patients with obesity. They can profoundly affect patients because they often require readmission, additional surgical interventions, lengthy intravenous antibiotic administration, and delayed rehabilitation. Negative pressure wound therapy (NPWT) exposes the wound site to negative pressure, resulting in the improvement of blood supply, removal of excess fluid, and stimulation of cellular proliferation of granulation tissue. This study aims to assess the incidence of wound dehiscence and SSIs in patients with obesity undergoing TKA after the routine use of NPWT. This sduty enrolled adult patients with obesity who underwent TKA within 8 years. A total of 360 adult patients with obesity (NPWT: 150, non-NPWT: 210) underwent TKA, and the baseline characteristics were similar between the 2 groups. Compared with the non-NPWT group, the NPWT group had a 50% lower incidence of wound dehiscence (3.33% vs 9.52%; P < .05) and a significantly lower incidence of SSIs (11.33% vs 25.24%; P < .05), including prosthetic joint infection (4.0% vs 10.0%; P < .05) and superficial wound infection (7.33% vs 15.24%; P < .05). In addition, the NPWT group had a lower need to return to the operating room for new interventions for any reason (2.67% vs 9.05%; P = .0107) than the non-NPWT group. Conventional incision NPWT can significantly reduce the incidence of wound dehiscence and SSIs in patients with obesity after TKA.

Piezo1 is a mechanically activated, non-selective cation channel characterized by its exquisite sensitivity to membrane tension and high permeability to calcium(Ca²⁺⁾, enabling the conversion of mechanical stimuli into intracellular signaling events. Activation of Piezo1 leads to Ca²⁺ influx, which initiates iron metabolism reprogramming—including transferrin receptor 1(TfR1)-dependent iron uptake, divalent metal transporter 1(DMT1)-mediated iron transport, and Nuclear Receptor Coactivator 4(NCOA4)-regulated ferritinophagy—thereby promoting the accumulation of reactive oxygen species (ROS) and lipid peroxidation. Ultimately, these events culminate in ferroptosis by suppressing glutathione peroxidase 4 (GPX4) activity. The “mechanical force–Piezo1–Ca²⁺–iron/lipid metabolism” axis establishes mechanical stress as a pivotal upstream regulator of ferroptosis. This axis facilitates the functional integration of mechanotransduction into inflammatory mediator production, vascular and extracellular matrix(ECM) remodeling, and metabolic reprogramming. Furthermore, this signaling pathway exerts context-dependent pathogenic or protective effects across diverse pathological conditions, including musculoskeletal degeneration, ischemia-reperfusion injury, inflammatory bowel disease, neurovascular disorders, and cancer. This review provides a comprehensive overview of the molecular mechanisms and clinical evidence governing Piezo1-mediated ferroptosis. We summarize current pharmacological and genetic interventions for its inhibition—along with associated limitations such as selectivity and pharmacokinetic challenges—and explores interventions targeting the channel itself, Ca²⁺signaling, and downstream ferroptotic processes, including iron chelation, lipid peroxidation suppression, and preservation of the GPX4/coenzyme Q10 (CoQ10) axis. Furthermore, the potential for integrating these interventions with established therapeutic modalities is also discussed. A profound understanding of the druggability and context-dependent dynamics of the Piezo1-ferroptosis axis is expected to facilitate the discovery of novel therapeutic targets and combinatorial regimens for the precision management of mechanosensitive diseases.

Background/Objectives: Dysregulated macrophage M1/M2 polarization is implicated in glucocorticoid-induced osteonecrosis of the femoral head (GONFH). Reprogramming M1 to M2 macrophages represents a potential therapeutic strategy. Kaempferol (KPF), a natural flavonoid with anti-inflammatory properties, may offer benefits, but its mechanism in GONFH is unknown. Purpose: This study aims to explore the therapeutic impact of KPF on GONFH and the mechanisms involved. Methods: In vitro, macrophage viability (CCK-8 assay) and polarization (RT-qPCR, flow cytometry) were assessed. Conditioned medium from KPF-treated macrophages was co-cultured with BMSCs and HUVECs to evaluate osteogenic and angiogenic effects. Mechanisms were analyzed using Western blot, immunofluorescence, and flow cytometry. A rat GONFH model validated in vivo effects. Results: In vitro experiments revealed that KPF significantly augmented the ratio of M2 macrophages while concurrently diminishing the proportion of M1 macrophages. The conditioned medium derived from macrophages treated with KPF markedly improved the osteogenic and angiogenic capabilities of BMSCs and HUVECs. Immunofluorescence staining and Western blot revealed that KPF regulated macrophage polarization by enhancing mitophagy, which was reversed by the addition of a mitophagy inhibitor. Further experiments confirmed that KPF activated mitophagy by inhibiting the RhoA/ROCK signaling pathway. In vivo, KPF increased the proportion of M2 macrophages and promoted the expression of osteogenic and angiogenic markers. Conclusions: In conclusion, our study demonstrates that KPF alleviates GONFH by modulating macrophage M1/M2 polarization through RhoA/ROCK-mediated mitophagy activation. These findings provide novel insights into the treatment of GONFH.