Surgical flaps are basic tools in reconstructive surgery. Their use may be limited by ischemia and necrosis. Few therapies address or prevent them. Genetic therapy could improve flap outcomes, but primary studies in this field present conflicting results. This systematic review and meta-analysis aimed to appraise the efficacy of external gene delivery to the flap for its survival in preclinical models. This review was registered with PROSPERO (CRD42022359982). PubMed, Embase, Web of Science, and Scopus were searched to identify studies using animal models reporting flap survival outcomes following any genetic modifications. Random-effects meta-analysis was used to calculate mean differences in flap survival with accompanying 95% CI. The risk of bias was assessed using the SYRCLE tool. Subgroup and sensitivity analyses were performed to ascertain the robustness of primary analyses, and the evidence was assessed using the GRADE approach. The initial search yielded 690 articles; 51 were eventually included, 36 of which with 1576 rats were meta-analyzed. VEGF gene delivery to different flap types significantly improved flap survival area by 15.66% (95% CI 11.80–19.52). Other interventions had smaller or less precise effects: PDGF—13.44% (95% CI 3.53–23.35); VEGF + FGF—8.64% (95% CI 6.94–10.34); HGF—5.61% (95% CI 0.43–10.78); FGF 3.84% (95% CI 1.13–6.55). Despite considerable heterogeneity, moderate risk of bias, and low quality of evidence, the efficacy of VEGF gene therapy remained significant in all sensitivity analyses. Preclinical data indicate that gene therapy is effective for increasing flap survival, but further animal studies are required for successful clinical translation.

Diabetes mellitus (DM) severely impairs skin wound healing capacity, yet few treatment options exist to enhance this process. N-acetylcysteine (NAC) is an antioxidant that improves cellular proliferation and enhances wound healing in healthy animals, yet its use in the context of type II DM has not been studied. The aim of our research was to investigate the effect of topically applied NAC-enriched hydrogels on wound healing in a leptin-deficient murine wound model. Four excisional wounds were created on the backs of 20 db/db mice and were subsequently treated with hydrogels containing NAC at concentrations of 5%, 10% and 20% or placebo (control). Healing was monitored for 28 days; photographs of the wounds were taken on every third day. Wound tissues were harvested on days 3, 7, 14 and 28 to undergo histological examinations. Wounds treated with 5% NAC showed improved wound closure speed accompanied by an increased dermal proliferation area on microscopic assessment compared with other groups. Higher concentrations of NAC failed to show a beneficial effect on wound healing. 5% NAC improved early stages of wound healing in a murine model of type II DM by increasing wound closure speed, likely mediated by improved dermal proliferation.

The objective of this study was to investigate if delivering multiple doses of N-acetylcysteine (NAC) post-surgery in addition to pre-incisional administration significantly impacts the wound healing process in a rat model. Full-thickness skin incisions were carried out on the dorsum of 24 Sprague-Dawley rats in six locations. Fifteen minutes prior to the incision, half of the sites were treated with a control solution, with the wounds on the contralateral side treated with solutions containing 0.015%, 0.03% and 0.045% of NAC. In the case of the NAC treated group, further injections were given every 8 h for three days. On days 3, 7, 14 and 60 post-op, rats were sacrificed to gather material for the histological analysis, which included histomorphometry, collagen fiber organization analysis, immunohistochemistry and Abramov scale scoring. It was determined that scars treated with 0.015% NAC had significantly lower reepithelization than the control at day 60 post-op (p = 0.0018). Scars treated with 0.045% NAC had a significantly lower collagen fiber variance compared to 0.015% NAC at day 14 post-op (p = 0.02 and p = 0.04) and a lower mean scar width than the control at day 60 post-op (p = 0.0354 and p = 0.0224). No significant differences in the recruitment of immune cells and histological parameters were found. The results point to a limited efficacy of multiple NAC injections post-surgery in wound healing.

Patients with unstable angina present clinical characteristics of atherosclerotic plaque vulnerability, contrary to chronic coronary syndrome patients. The process of athersclerotic plaque destabilization is also regulated by microRNA particles. In this study, the investigation on expression levels of microRNAs inhibiting the expression of proteins that protect from atherosclerotic plaque progression (miR-92a inhibiting KLF2, miR-10b inhibiting KLF4, miR-126 inhibiting MerTK, miR-98 inhibiting IL-10, miR-29b inhibiting TGFβ1) was undertaken. A number of 62 individuals were enrolled—unstable angina (UA, n = 14), chronic coronary syndrome (CCS, n = 38), and healthy volunteers (HV, n = 10). Plasma samples were taken, and microRNAs expression levels were assessed by qRT-PCR. As a result, the UA patients presented significantly increased miR-10b levels compared to CCS patients (0.097 vs. 0.058, p = 0.033). Moreover, in additional analysis when UA patients were grouped together with stable patients with significant plaque in left main or proximal left anterior descending (“UA and LM/proxLAD” group, n = 29 patients) and compared to CCS patients with atherosclerotic lesions in other regions of coronary circulation (“CCS other” group, n = 25 patients) the expression levels of both miR-10b (0.104 vs. 0.046; p = 0.0032) and miR-92a (92.64 vs. 54.74; p = 0.0129) were significantly elevated. In conclusion, the study revealed significantly increased expression levels of miR-10b and miR-92a, a regulator of endothelial protective KLF factors (KLF4 and KLF2, respectively) in patients with more vulnerable plaque phenotypes.

Surgical flaps are rudimentary tools in reconstructive surgery, especially following extensive solid tumour resections. They cover skin and soft tissue defects but are prone to ischaemia and necrosis. Since their primary aim is reconstruction, they rarely exhibit a therapeutic activity against the treated disease. Attempts have been made to develop a new therapeutic strategy—biologic brachytherapy, which uses genetically engineered surgical flaps as a drug delivery vehicle, allowing the flap tissue to act as a “biologic pump”. This systematic review summarizes the preclinical evidence on using genetically modified surgical flaps. A literature search was conducted in PubMed, EMBASE, Scopus and Web of Science. The initial literature search yielded 714 papers, and, eventually, seventy-seven studies were included in qualitative analysis. The results show that genetic enhancement of flaps has been used as a local or systemic therapy for numerous disease models. Frequently, it has been used to increase flap survival and limit ischaemia or promote flap survival in a non-ischemic context, with some studies focusing on optimizing the technique of such gene therapy. The results show that genetically modified flaps can be successfully used in a variety of contexts, but we need more studies to implement this research into specific clinical scenarios.