Impact of Nicotine Replacement Therapy on Breast Surgery Outcomes.

BACKGROUND: Smoking cessation therapy, including nicotine replacement therapy (NRT), is used perioperatively to assist patients to reduce their tobacco smoke intake and consequently decrease their risk of smoking-associated complications. There are, however, theoretical concerns that nicotine-induced peripheral vasoconstriction could impair wound healing. This study investigated the effect of NRT on postoperative outcomes in patients undergoing breast surgery. METHODS: A retrospective chart review of patients undergoing breast surgery within the Yale New Haven Health System from the years 2014 to 2020 was performed. Documented smoking status within 6 months before surgery, use or prescription of NRT, type of surgery, and surgical complications of infection, wound dehiscence, tissue necrosis, hematoma, seroma, fat necrosis, and return to operating room within 30 days were recorded. Demographic and complication data were compared between patients with NRT usage and those without using t-tests and chi-square analyses. Multivariable logistic regression models were created to predict the effect of NRT usage on the occurrence of any complication. RESULTS: A total of 613 breast procedures met inclusion criteria, of which 105 (17.2%) had documented NRT use. The NRT cohort and the non-NRT cohort were well balanced with respect to demographics and procedural variables. Upon multivariable modeling for risk of any surgical complication, NRT was not a significant predictor (odds ratio [OR]: 1.199, p = 0.607 and OR: 0.974, p = 0.912, respectively), whereas procedure type, increased body mass index, and increased age were. CONCLUSION: NRT use was not associated with an increased risk of postoperative complications compared with not using NRT as part of smoking cessation therapy prior to operation.

Regenerative Approaches for Chronic Wounds.

Chronic skin wounds are commonly found in older individuals who have impaired circulation due to diabetes or are immobilized due to physical disability. Chronic wounds pose a severe burden to the health-care system and are likely to become increasingly prevalent in aging populations. Various treatment approaches exist to help the healing process, although the healed tissue does not generally recapitulate intact skin but rather forms a scar that has inferior mechanical properties and that lacks appendages such as hair or sweat glands. This article describes new experimental avenues for attempting to improve the regenerative response of skin using biophysical techniques as well as biochemical methods, in some cases by trying to harness the potential of stem cells, either endogenous to the host or provided exogenously, to regenerate the skin. These approaches primarily address the local wound environment and should likely be combined with other modalities to address regional and systemic disease, as well as social determinants of health.

Coronavirus Disease 2019 and the Yale Response: A Semistructured Interview Study on Plastic Surgery Resident Education and Departmental Adaptation to the Lockdown.

BACKGROUND: Sooner-than-expected progression to statewide lockdown at the height of the coronavirus disease 2019 pandemic left minimal time for medical specialty boards, including The American Board of Plastic Surgery, to issue guidance for their respective programs. As a result, programs were tasked with developing creative alternatives to their standard resident curricula and department schedules. OBJECTIVE: To capture attending and resident experience of the coronavirus disease 2019 lockdown in narrative form and to understand what specific changes enacted to maintain adequate education should be considered for continuation after the pandemic's conclusion. METHODS: Qualitative, semistructured interviews of residents, fellows, and faculty of the Section of Plastic and Reconstructive Surgery during 2019 to 2020 academic year were conducted on the following topics: (1) general reflection on lockdown, (2) resident maintenance of daily logs, (3) multi-institutional collaborative lectures, (4) modified didactic curriculum, (5) virtual 3-dimensional craniofacial planning sessions, (6) maintenance of department camaraderie, and (7) effect on preparation to become a surgeon. RESULTS: Twenty interviews (response rate 77%) were conducted between October 2020 and February 2021. Of residents, 100% felt observing the craniofacial planning sessions was beneficial, with many explicitly noting it provided a unique perspective into the surgeon's thought process behind planned manipulations, to which they usually are not privy. Of residents, 100% felt confident at the time of the interview that the lockdown would have no lasting effects on their preparation to become a surgeon. CONCLUSIONS: Rapid changes enacted at Yale enabled resident training to advance, and documentation of the success of these changes can inform future curriculum design.

The Impact of Social Determinants of Health on Pressure Injury Progression: A Retrospective Chart and Scoping Review.

OBJECTIVE: To understand the effects of nutrition security and social determinants of health (SDOHs) on pressure injury (PI) progression through a scoping review and retrospective review of patients reporting to New England's largest healthcare system. METHODS: Authors performed a scoping review for full-text, original articles reporting outcomes data specific to PIs in patients with socially informed nutrition insecurity. Investigators also performed a retrospective review of all patients from 2012 to 2021 to search for patients with PI documentation and International Classification of Diseases, Tenth Revision Z codes related to the SDOHs. RESULTS: A full-text review of 2,323 articles from 1965 to 2020 failed to locate any eligible studies. Investigators identified 1,044 patients who met the inclusion criteria; 50.7% were men, 74.3% were White, and 13.3% had evidence of detrimental SDOHs. The average PI duration was 12.13 days (interquartile range, 6 days). Multivariate regression analysis revealed that PI duration was longer in men, Black patients, and patients with evidence of detrimental SDOHs compared with their converse counterparts (P < .0001). The presence of detrimental SDOHs independently predicted an increased duration of disease by 13.07 days (95% CI, 8.99-17.15; t = 6.29, P < .0001). CONCLUSIONS: A patient's SDOH history has a significant and considerably stronger correlation with disease progression than predictors that are traditionally studied such as sex, race, or body mass index. These findings are novel, as highlighted by the absence of data uncovered in the literature. These data carry relevance for plastic surgeons wishing to prevent early recurrence following operative closure of PI-related wounds.

Does the Presence of a Preexisting Open Wound Increase Complication Risk for Implant Procedures?

ABSTRACT: Despite limited evidence, a common belief in surgical practice is that patients should not undergo elective surgery until any open wounds heal because of the risk of seeding infection to the new surgical site. To our knowledge, this is the first study to analyze postoperative complication rates for implants placed in the context of open wounds using the American College of Surgeons National Surgical Quality Improvement Program database. We examined 30-day postoperative infections for breast, hip, knee, and spine implants using the 2012-2016 American College of Surgeons National Surgical Quality Improvement Program database. Patients were excluded for missing data and propensity matched 1:10 for demographics and comorbidities to minimize confounders. Complication rates were assessed using Pearson χ2 tests. Of 475,101 patients who received breast, hip, knee, or spine implants, 1491 did so with an open wound. After propensity score matching, the overall complication rate remained higher with the open wound cohort (6.7% vs 3.8%, P < 0.001). Although the presence of an open wound was associated with an increased risk of superficial surgical site infection, it was not associated with an increased risk of organ space surgical site infection, the site best correlated with infection at the implant. Nor was the presence of an open wound associated with a statistically significantly increased risk of deep incisional surgical site infection or wound dehiscence. After controlling for demographics, preoperative comorbidities, and surgical factors, the presence of an open wound before implant surgery is associated with an increased risk of complications, readmission, and reoperation, but not necessarily infection at the surgical site.

Prelamination of Vascularized Tensor Fascia Lata for Complex Abdominal Wall Reconstruction.

ABSTRACT: There are 2 to 5 million laparotomies performed in the United States annually. Of these, 250,000 to 350,000 will undergo a ventral hernia repair. Repairs are often complicated by recurrence and infection. These risks are significantly increased in previously infected repairs, with reported recurrence rates varying from 17% to 28% after repair of infected ventral hernias, double the rates reported for first-time uninfected repairs. We describe here a novel treatment strategy involving the creation then use of bilateral prelaminated permanent mesh-reinforced tensor fascia latae flaps for abdominal wall reconstruction in patients who have recurrent ventral hernias and had undergone previous repairs complicated by infection. Previous repairs included anterior components separation, thereby making subsequent fascial release techniques and achievement of a reinforced repair extremely unlikely. Three patients were treated by a single surgeon using this 2-stage technique. There have been no incidences of recurrence and no infections after 2 to 10 years. In these patients, the only conventional option would have been a bridged repair with absorbable mesh. Combining the advantages of permanent mesh and well-vascularized autologous tissue optimizes the repair's tensile strength while mitigating the chance of recurrent infection associated with the use of permanent mesh. We propose that this strategy may be an appropriate treatment option for patients with recurrent ventral hernias that have not responded to other conventional modalities of treatment.

An in situ collagen-HA hydrogel system promotes survival and preserves the proangiogenic secretion of hiPSC-derived vascular smooth muscle cells.

Human-induced pluripotent stem cell-derived vascular smooth muscle cells (hiPSC-VSMCs) with proangiogenic properties have huge therapeutic potential. While hiPSC-VSMCs have already been utilized for wound healing using a biomimetic collagen scaffold, an in situ forming hydrogel mimicking the native environment of skin offers the promise of hiPSC-VSMC mediated repair and regeneration. Herein, the impact of a collagen type-I-hyaluronic acid (HA) in situ hydrogel cross-linked using a polyethylene glycol-based cross-linker on hiPSC-VSMCs viability and proangiogenic paracrine secretion was investigated. Our study demonstrated increases in cell viability, maintenance of phenotype and proangiogenic growth factor secretion, and proangiogenic activity in response to the conditioned medium. The optimally cross-linked and functionalized collagen type-I/HA hydrogel system developed in this study shows promise as an in situ hiPSC-VSMC carrier system for wound regeneration.

Evidence-Based Gardening: Using Palliative Approaches to Cure Complex Wounds.

Complex wounds are commonly thought to require aggressive surgical intervention to achieve healing. However, optimal healing results can often be achieved when greater emphasis is placed on optimizing patient factors prior to any surgical intervention. A retrospective review was performed of pressure ulcers and complex wound cases treated over 5 years at the Yale New Haven Wound Center. Optimal healing including clinical resolution of osteomyelitis and improved scarring was achieved when patient factors, such as glucose control and nutrition, were optimized. Surgical intervention can be more effective and even avoided entirely with the appropriate focus on optimizing patient factors.

Can Nicotine Replacement Therapy Decrease Complications in Plastic Surgery?

Cigarette smoking has been well demonstrated to be associated with adverse outcomes and increased complications in surgical patients in the operative and postoperative periods. There is general agreement that smoking cessation decreases such risks; however, much debate still exists regarding the most effective modalities for risk mitigation, especially concerning modalities involving nicotine replacement in some form. This article reviews the discussion regarding smoking cessation therapies, in particular those involving nicotine replacement, in the context of mitigating risk in plastic surgery procedures. The recent rise in popularity of electronic cigarettes poses further challenges for clinicians in minimizing risk and optimizing outcomes for patients. Prospective studies including high-level evidence such as randomized controlled clinical trials will be required to help plastic surgeons develop guidelines that will enable optimization of patient safety and clinical outcomes.

Targeting Fibrotic Signaling: A Review of Current Literature and Identification of Future Therapeutic Targets to Improve Wound Healing.

Fibrosis is a consequence of aberrant wound healing processes that can be debilitating for patients and often are associated with highly morbid disease processes. Myofibroblasts play an important role in determining an appropriate physiologic response to tissue injury or an excessive response leading to fibrosis. Specifically, "supermature" focal adhesions, α-smooth muscle actin, and the myocardin-related transcription factor/serum response factor pathway likely play a significant role in the differentiation and survival of myofibroblasts in fibrotic lesions. Thus, targeting each of these and disrupting their functioning could lead to the development of therapeutic options for patients suffering from fibrosis and other sequelae of dysregulated wound healing. In this paper, we review the current literature concerning the roles of these three constituents of fibrotic signaling pathways, work already done in attempting to regulate these processes, and discuss the potential of these biomolecular constituents as therapeutic targets in future translational research.

An Algorithm for the Management of Residual Head and Neck Melanoma In Situ Using Topical Imiquimod: A Pilot Study.

INTRODUCTION: Melanoma in situ (MIS) is an early variant of melanoma in which the disease is limited to the epidermis. Standard therapy is currently surgical excision with at least 5-mm margins. In some instances, there are large or anatomically difficult lesions where complete excision will result in significant esthetic or functional impairment. Our experience has shown a 6-week course to be sufficient in certain patients compared with the suggested 12-week course. In this context, we propose a shortened duration of treatment of positive margins with topical imiquimod and propose an algorithm that results in the least amount of dysfunction for the patient. METHODS: Our inclusion criteria were patients undergoing excision of a lesion found to have postsurgical margins, which were positive for MIS. Patients applied 5% imiquimod 3 to 5 times per week for at least 6 weeks at the site of the positive margin(s). Duration and frequency of treatment were titrated based on response. A reexcision skin biopsy using 1-mm margins was performed after residual inflammation subsided. Our endpoints were recurrence and effectiveness with length of treatment. RESULTS: Sixteen patients met our criteria. All patients were found to have MIS in the margins after surgical excision. Twelve of those lesions were classified as MIS in the initial biopsy; the remaining 4 were either melanoma stage T1A or T1B. Mean follow-up time was 14.3 months, and 1 patient was lost to follow-up. We had 3 patients without response, and of these, 1 was found to have atypical squamous cell carcinoma and the other had a recurrence of MIS. Cure rate after use of topical imiquimod was 93.3% (14/15). DISCUSSION: The proposed algorithm for the treatment of residual disease in head and neck melanoma and MIS using topical imiquimod offers various advantages. This anatomical region is cosmetically sensitive, and the option of using 1 mm versus 5 mm reexcision margins after imiquimod treatment yields comparable cure rates with less tissue excised overall. Our algorithm demonstrates that 6 weeks of active inflammation provides comparable results with the traditional 12-week course. This decreased treatment time reduces patient discomfort and improves patient adherence.

Clinical Value of Single-photon Emission Computed Tomography Combined With Computed Tomography for Sentinel Lymph Node Identification in Melanoma.

INTRODUCTION: Melanoma is the deadliest form of skin cancer and has the ability to metastasize widely. Accurate diagnosis of sentinel lymph nodes (SLN) is crucial to its management. The gold standard for SLN identification is planar lymphoscintigraphy. Recently, single-photon emission computed tomography combined with computed tomography (SPECT/CT) has been used as a hybrid method to map lymphatic drainage networks. We aim to better characterize the utility of this tool in head and neck melanoma by evaluating its effectiveness in the preoperative setting for melanoma patients undergoing sentinel lymph node biopsy (SLNB). METHODS: We performed a retrospective chart review at the West Haven Veterans Affairs Hospital. Inclusion criteria were patients with melanoma with a thickness greater than 0.75 mm and SPECT/CT use before operative sentinel lymph node excision. Exclusion criteria included clinically palpable lymph nodes, evidence of distant metastatic disease, melanoma with a Breslow depth less than 0.75 mm, and melanoma in situ. Our primary endpoints were correlation with intraoperative findings and whether the test had any influence on the operative plan. RESULTS: Thirty-five patients between 2011 and 2017 met our criteria. SPECT/CT correlated with the sentinel node biopsy based on intraoperative lymphoscintigraphy in 30 (86%) of 35 cases, and there were no changes to the operative plan after SPECT/CT was performed. Sentinel lymph nodes were correctly identified in all 35 cases. CONCLUSIONS: The role of SPECT/CT in SLNB is uncertain. According to some studies, SPECT/CT can help decision making and change surgical approach in up to 35% of patients. However, other studies have reported questionable correlation with intraoperative findings and no added intraoperative value in over 50% of patients. We have demonstrated that preoperative SPECT/CT was consistent with intraoperative findings in 86.0% of cases but did not change the surgical approach for the SLNB. Surveillance over a period of 12 months did not reveal any signs of melanoma recurrence. A possible advantage of SPECT/CT is potentially decreasing costs by lowering operative time. However, financial cost in the literature suggests SPECT/CT is costlier than lymphoscintigraphy and therefore this must be weighed against any potential benefit. Overall, we did not find that SPECT/CT gives added value when compared with lymphoscintigraphy.

Incisional Negative Pressure Wound Therapy Augments Perfusion and Improves Wound Healing in a Swine Model Pilot Study.

BACKGROUND: A commonly used treatment for open wounds, negative pressure wound therapy (NPWT) has recently been used to optimize wound healing in the setting of surgically closed wounds; however, the specific mechanisms of action by which NPWT may benefit patients after surgery remain unknown. Using a swine wound healing model, the current study investigates angiogenesis as a candidate mechanism. METHODS: Multiple excisional wounds were created on the dorsa of 10 male Yorkshire pigs and closed by primary suture. The closed wounds underwent treatment with either NPWT dressing or control dressings in the absence of negative pressure. Dressings were maintained for 8 days followed by euthanasia of the animal. Scar evaluation of the wounds by photographic analysis was performed, and wounds were analyzed for angiogenesis markers by enzyme-linked immunosorbent assay and immunohistochemistry. RESULTS: Scar evaluation scores were observed to be significantly higher for the NPWT-treated sites compared with the control sites (P < 0.05). The enzyme-linked immunosorbent assay results demonstrated increases for vascular endothelial growth factor (VEGF) staining at the incision site treated with NPWT compared with other treatment groups (P < 0.05). In addition, an approximately 3-fold elevation in VEGF expression was observed at the NPWT-treated sites (2.8% vs. 1%, respectively; P < 0.0001).). However, there was no significant difference in immunohistochemistry staining. CONCLUSIONS: The use of NPWT improves the appearance of wounds and appears to increase VEGF expression after 8 days in the setting of a closed excisional wound model, suggesting that improved angiogenesis is one mechanism by which NPWT optimizes wound healing when applied to closed surgical wound sites.

The Impact of Microbial Communities on Wound Healing: A Review.

Chronic, nonhealing wounds place an enormous burden on both the health care system and patients, with no definitive treatments available. There has been increasing evidence that the microbial composition of wounds may play an important role in wound healing. Culture-independent methods for bacterial detection and analysis have revealed the wound microbiome to be much more diverse and complex than culture alone. Such methods primarily rely on targeted amplification and sequencing of various hypervariable regions of the bacterial 16S rRNA for phylogenetic analysis. To date, there have been several studies utilizing culture-independent methods to investigate the microbiome of a variety of chronic wounds, including venous insufficiency ulcers, pressure ulcers, and diabetic foot ulcers. Major bacteria found include Staphylococcus, Streptococcus, Corynebacterium, Pseudomonas, and various anaerobes. Current studies suggest that improved healing and outcomes may be correlated with increased bacterial diversity and instability of the microbiome composition of a wound. However, the exact role of the microbiome in wound healing remains poorly understood. While the current research is promising, studies are very heterogeneous, hindering comparisons of findings across different research groups. In addition, more studies are needed to correlate microbiome findings with clinical factors, as well as in the relatively unexplored fields of acute wounds and nonbacterial microbiomes, such as the wound mycobiome and virome. Better understanding of the various aspects of the microorganisms present in wounds may eventually allow for the manipulation of the wound microbiota in such a way as to promote healing, such as through bacteriophage therapies or probiotics.

Impact of Acellular Dermal Matrix on Postsurgical Wound Fluid Biomarkers in Prosthetic Breast Reconstruction.

BACKGROUND: Despite the widespread practice of using biologic scaffolds for soft tissue reinforcement over prosthetic implants, the impact of acellular dermal matrix (ADM) on surgical wound fluid biomarkers over the initial postoperative period after prosthetic breast reconstruction remains poorly understood. METHODS: Patients undergoing prosthetic breast reconstruction surgery where ADM was likely to be used were consented to have fluid samples collected from surgical drains after surgery. Sample collections occurred at an "Early" time point at 24 to 48 hours after surgery and then a "Late" time point approximately 1 to 2 weeks after surgery. All procedures were performed by a single surgeon. Acellular dermal matrix was placed when prosthetic coverage with autologous tissue could not be achieved. Laboratory analyses were performed in blinded fashion without the knowledge of whether the samples came from the ADM "Present" or "Not Present" group. RESULTS: Twenty-one patients were in the ADM Present group and 18 patients were in the Not Present group. Both groups showed similar demographics based on age and body mass index. Analyses for cell concentration, protein concentration, extracellular matrix protein levels, cell proliferation activity, and matrix metalloproteinase activity showed no significant differences between wound fluid samples from the 2 groups. CONCLUSIONS: The presence of ADM does not appear to significantly impact wound biomarkers in prosthetic breast reconstruction. The current study provides useful data regarding the impact of ADM on surgical wound fluid during the initial postoperative period, laying important groundwork for more extensive future studies on the impact of biologic scaffolds on wound biology.

On Beyond Lidocaine: Reconsidering Local Anesthetics in Tumescent Liposuction-A Critical Review.

The use of tumescent solution in liposuction is now considered standard of care; however, much debate still exists regarding its ideal components, especially surrounding the inclusion of local anesthetics. This article reviews the discussion regarding the use of local anesthetics in tumescent liposuction and how it may evolve in the future. The need for local anesthetic additives in tumescent liposuction has been questioned, and the use of longer-acting agents discouraged; however, increasing number of reports in recent years have described the increasingly widespread use of tumescent anesthesia where a wetting solution is infiltrated to achieve anesthesia in an operative field for procedures other than liposuction. More high-level evidence, such as randomized controlled clinical trials, will be required; however, it should be possible to develop a useful standardized algorithm that can guide surgeons to optimize patient safety as well as patient experience.

SDF-1 liposomes promote sustained cell proliferation in mouse diabetic wounds.

Chronic skin wounds are a common complication of diabetes. When standard wound care fails to heal such wounds, a promising approach consists of using decellularized matrices and other porous scaffold materials to promote the restoration of skin. Proper revascularization is critical for the efficacy of such materials in regenerative medicine. Stromal cell-derived factor-1 (SDF-1) is a chemokine known to play a key role for angiogenesis in ischemic tissues. Herein we developed nanosized SDF-1 liposomes, which were then incorporated into decellularized dermis scaffolds used for skin wound healing applications. SDF-1 peptide associated with liposomes with an efficiency of 80%, and liposomes were easily dispersed throughout the acellular dermis. Acellular dermis spiked with SDF-1 liposomes exhibited more persistent cell proliferation in the dermis, especially in CD31(+) areas, compared to acellular dermis spiked with free SDF-1, which resulted in increased improved wound closure at day 21, and increased granulation tissue thickness at day 28. SDF-1 liposomes may increase the performance of a variety of decellularized matrices used in tissue engineering.

Local anesthetic use in tumescent liposuction: an American Society of Plastic Surgeons survey.

BACKGROUND: Current guidelines favor the use of lidocaine in liposuction wetting solutions. The use of bupivacaine as an alternative remains controversial despite reports of its use with safe and favorable outcomes suggesting faster postoperative recovery time secondary to improved pain control. The goals of this study were to determine the prevalence of bupivacaine use, examine liposuction practices of bupivacaine users, and elucidate opinions regarding bupivacaine use. METHODS: An online survey was distributed to 2500 randomly selected members of the American Society of Plastic Surgeons. Data were collected and analyzed with special attention toward the practice and opinions of bupivacaine use. RESULTS: The response rate of the survey met the average American Society of Plastic Surgeons online survey response rate at 12.8% (n=320). Respondents (7.2%; n=22) reported using bupivacaine in their wetting solutions (bupivacaine group) and provided a dosage range of 62.5 to 150 mg. Respondents (83.5%; n=254) reported using either lidocaine or prilocaine (no-bupivacaine group). There were no reports of bupivacaine toxicity in 2011. The demographic profile and liposuction practices of both groups were comparable. Although 36% of the no-bupivacaine group did not know or had no opinion on when it is appropriate to use bupivacaine in liposuction wetting solutions, 85% of this group has used bupivacaine for other clinical purposes. CONCLUSIONS: A review of 320 plastic surgeons' experiences revealed that 7% of respondents are using bupivacaine in their tumescent solutions with no reported cases of toxicity. Bupivacaine users differed dramatically only in their opinion regarding the safety of bupivacaine in tumescent liposuction. The recent studies suggesting better postoperative pain control with bupivacaine along with the proportion of respondents reporting bupivacaine use call for distinct guidelines on bupivacaine use in liposuction. Further studies, including a rigorous clinical trial documenting the safety and efficacy of bupivacaine when compared with lidocaine, would be warranted.

The fate of internalized α5 integrin is regulated by matrix-capable fibronectin.

BACKGROUND: Assembly of fibronectin matrices is associated with integrin receptor turnover and is an important determinant of tissue remodeling. Although it is well established that fibronectin is the primary ligand for α5ß1 receptor, the relationship between fibronectin matrix assembly and the fate of internalized α5 integrin remains poorly characterized. MATERIALS AND METHODS: To evaluate the effect of fibronectin matrix on the fate of internalized α5 integrin, fibronectin-null Chinese hamster ovary and mouse embryo fibroblast cells were used to track the fate of α5 after exposure to exogenous fibronectin. RESULTS: In the absence of matrix-capable fibronectin dimer, levels of internalized α5 decreased rapidly over time. This correlated with a decline in total cellular α5 and was associated with the ubiquitination of α5 integrin. In contrast, internalized and total cellular α5 protein levels were maintained when matrix-capable fibronectin was present in the extracellular space. Further, we show that ubiquitination and degradation of internalized α5 integrin in the absence of fibronectin require the presence of two specific lysine residues in the α5 cytoplasmic tail. CONCLUSIONS: Our data demonstrate that α5 integrin turnover is dependent on fibronectin matrix assembly, where the absence of matrix-capable fibronectin in the extracellular space targets the internalized receptor for rapid degradation. These findings have important implications for understanding tissue-remodeling processes found in wound repair and tumor invasion.

Cellular therapeutics and immunotherapies in wound healing - on the pulse of time?

Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring significant human and financial resources. Chronic wounds arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, and genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization and the formation of biofilms. Infection, consequently, perpetuates a chronic inflammatory microenvironment, preventing the progression and completion of normal wound healing. The current standard of care (SOC) for chronic wounds involves surgical debridement along with localized wound irrigation, which requires inpatient care under general anesthesia. This could be followed by, if necessary, defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft, local, or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored. To promote physiological wound healing, a variety of approaches have been subjected to translational research. Beyond conventional wound healing drugs and devices that currently supplement treatments, cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell- or molecule-specific wound healing properties. However, in contrast to the clinical omnipresence of chronic wound healing disorders, there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds. This review provides a comprehensive exploration of current therapies, experimental approaches, and translational studies, offering insights into their efficacy and limitations. Ultimately, we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.