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Background and Aim: Wound healing is a complex process comprised of several distinct phases. An imbalance in any of the stages creates a chronic wound with the potential to cause life-threatening complications for patients. Chitosan (CS) is a biopolymer that has shown to positively impact the different healing phases. This systematic review aimed to evaluate the anti-inflammatory and immunomodulatory properties of CS-based wound therapy for the skin healing process after an injury., Methods: A systematic review was conducted in November 2021 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The PubMed, Embase, Google Scholar, and Cochrane online databases were queried to capture all publications in the past 10 years that investigated the CS effects on inflammation and immune reaction., Results: A total of 234 studies were screened after removing duplicates and 14 articles fulfilled our inclusion and exclusion criteria. In the studies, CS was combined with a wide range of products. One clinical trial was found that treated patients with diabetic foot ulcers. All animal models in the studies used a full-thickness skin wound to test the effectiveness of CS in the healing process. Decreased pro-inflammatory cytokine levels, a shortened inflammatory phase and accelerated wound closure was observed in all of the studies., Conclusions: CS proved to be a feasible, versatile, and multifaceted biomaterial that enhances the biological response to a skin injury. When combined with other products, its potential to boost the healing process through regulation of the inflammatory and cellular activity is increased., Relevance for Patients: Although few clinical trials have been completed, CS has become an excellent alternative to modulate the local inflammatory response promoting wound healing. Especially in patients with associated comorbidities that affect the typical resolution of skin healing, such as diabetes and vascular insufficiency. Therefore, using bioactive wound dressings based on CS combined with nanoparticles, growth factors, lived cells, or medications released in a controlled manner positively impacts patient life by shorting the wound healing process., Competing Interests: None., (Copyright: © 2022 Author(s).)

Background and Aim: Although a natural phenomenon, aging is a degenerative condition that promotes cellular malfunction and subsequent organ and body dysfunction. According to the World Health Organization, the elderly are the fastest growing age group worldwide. A 2012 population report stated that 43.1 million adults of 65 years or older lived in the United States, which is expected to jump to 83.7 million in 2050, placing an additional burden on an already stretched health-care network. Elderly patients broadly impact our health-care system, as reported in a 2014 wound report. 8.2 million patients were diagnosed with at least one type of wound, with patients 75 years or older making up most of the diagnoses. Aging affects all stages of the wound healing cascade. Although wound healing is downregulated in the elderly, scarce information exists regarding the effects of aging and flap survival in this group. Therefore, this study aims to report the impact of age on the survival of flaps in murine models. We hypothesize that increased aged animals will have decreased flap survival., Methods: A systematic review was performed on February 1, 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We searched for full-text articles written in English, consisting of experimental murine models that compared flap survival between aged and young animals, in the following databases: PubMed, Scopus, CINAHL, and Web of Science. The terms "mice" OR "rats" AND "surgical flaps" AND "aging" guided our search. Models affected by chronic diseases were excluded from the study., Results: Out of the 208 articles found by our search, seven were included according to our inclusion and exclusion criteria. Five studies used rats as experimental models, while the remaining two used mice. Local flaps were done in five studies, and two performed free flaps, transferring them from young and aged animals to young controls. Five articles reported lower flap survival in elder groups when exposed to ischemic insults. Three papers reported a deficiency in angiogenesis, vasculogenesis, and vascular reactivity as plausible causes for lack of survival, with one author correlating and verifying their results in human subjects. Although one article reported a lack of statistical power, they perceived a trend similar to the previous studies. Finally, one article reported inconclusive and variable results., Conclusion: Evidence suggests that a lack of angiogenic and vasculogenic response in conjunction with decreased vascular reactivity are responsible for the diminished survival of flaps in the elder. Therapeutic means to boost the angiogenic, vasculogenic, and vascular reactivity response to improve patient outcomes require further research to understand the time course and mechanisms of flap survival in the elderly., Relevance for Patients: All humans will feel the effects of aging one way or another. However, we can all agree that aging affects our basic biological processes, which negatively affects macroscopic appearance. One of the essential aspects downregulated in the elderly is their ability to respond to tissue injury and hypoxia, creating non-favorable circumstances for wound healing. Furthermore, to manage these non-healing wounds, flaps are raised to create a covering for these defects. However, age also impacts the ability of these flaps to survive, augmenting the problem and entering a vicious circle. To improve outcomes, we must focus our future research on understanding the basic principles of how aging affects the survival of flaps in elderly population., Competing Interests: None., (Copyright: © 2022 Author(s).)

Background and Aim: Lymph node transfer surgery (LNTS) is indicated in secondary lymphedema (LE) patients who do not respond to conservative therapy. Animal models are the spearhead of LE research and were used to pioneer most of the surgical interventions currently in practice. We conducted a systematic review of the literature to explore animal models dedicated to LNTS to compare different species, techniques, and outcomes., Methods: Four databases were searched: PubMed, Cumulative Index of Nursing and Allied Health Literature, Scopus, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as our basis of organization., Results: Avascular lymph node graft (ALNG) and vascularized lymph node transfer (VLNT) effectively treated LE and lead to better outcomes than controls. Whole ALNGs are superior to fragmented ALNGs. Larger fragments are more likely to be reintegrated into the lymphatic system than small fragments. VLNT was superior to whole and fragmented ALNG. Increasing the number of VLNT resulted in better outcomes. Adipose-derived stem cells improved outcomes of VLNT; vascular endothelial growth factor C and D and platelet-rich plasma improved outcomes for ALNG. Cryopreservation of lymph nodes (LNs) did not affect outcomes for ALNG. The critical ischemia and venous occlusion time for LN flaps were 4-5 and 4 h, respectively. The critical time for reperfusion injury was 2 h. Some of the novel models included venous LNT, and cervical adipocutaneous flap to groin., Conclusion: Current evidence from animals favors VLNT over other surgical interventions. Several pharmacological therapies significantly improved outcomes of ALNG and VLNT., Relevance to Patients: LE is a chronic condition affecting millions of patients worldwide. LNTS is becoming more popular as a LE treatment. Animal models have led the LE research for decades and developing new models for LE are essential for LE research. This systematic review aims to summarize the existing animal models dedicated to LNTS. We believe that this review is critical to guide researchers in the selection of the model that is best fit for their hypothesis-driven experiments., Competing Interests: None of the authors have any conflicts of interest., (Copyright: © 2022 Whioce Publishing Pte. Ltd.)

Background: Human adipose-derived stem cells (hADSCs) have gained attention lately because of their ease of harvesting and ability to be substantially multiplied in laboratory cultures. Stem cells are usually cultured under atmospheric conditions; however, preconditioning stem cells under hypoxic conditions seems beneficial., Aim: This systematic review aims to investigate the effect of hypoxia preconditioning and its impact on the proliferation and angiogenic capacity of the hADSCs., Methods: We performed a systematic review by searching PubMed, Scopus, Embase, and Google Scholar databases from all years through March 22, 2021, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Medical Subject Headings terms "adipose-derived stem cell," "Hypoxia," "cell proliferation," and "angiogenesis" guided our search. Only articles written in English using experimental models comparing a preconditioned group against a control group of hADSCs with data on proliferation and angiogenic capacity were included., Results: Our search yielded a total of 321 articles. 11 articles met our inclusion criteria and were ultimately included in this review. Two studies induced hypoxia using hypoxia-inducible factor-1 alpha stabilizing agents, while nine reached hypoxia by changing oxygen tension conditions around the cells. Four articles conducted in-vivo studies to correlate their in-vitro findings, which proved to be consistent. Although 1 article indicated cell proliferation inhibition with hypoxia preconditioning, the remaining 10 found enhanced proliferation in preconditioned groups compared to controls. All articles showed an enhanced angiogenic capacity of hADSCs after hypoxia preconditioning., Conclusion: In this review, we found evidence to support hypoxia preconditioning of hADSCs before implantation. Benefits include enhanced cell proliferation with a faster population doubling rate and increased secretion of multiple angiogenic growth factors, enhancing angiogenesis capacity., Relevance for Patients: Although regenerative therapy is a promising field of study and treatment in medicine, much is still unknown. The potential for angiogenic therapeutics with stem cells is high, but more so, if we discover ways to enhance their natural angiogenic properties. Procedures and pathologies alike require the assistance of angiogenic treatments to improve outcome, such is the case with skin grafts, muscle flaps, skin flaps, or myocardial infarction to mention a few. Enhanced angiogenic properties of stem cells may pave the way for better outcomes and results for patients., Competing Interests: The authors declare no conflict of interest, (Copyright: © Whioce Publishing Pte. Ltd.)