Alveolar Wound Research Articles

Spontaneous bacterial peritonitis and soft tissue healing after tooth extraction in liver cirrhosis patients

The objective of this study was to identify the association between tooth extraction and occurrence of spontaneous bacterial peritonitis (SBP) and to assess delayed soft tissue healing of extraction sockets in patients with cirrhosis. One hundred nineteen participants awaiting liver transplantation who required tooth extraction were included. Seven days before the surgery, the patients underwent panoramic radiography and laboratory examinations. Soft tissue healing was evaluated 7 days after the tooth extraction and medical records were checked after 21 days for development of SBP. The relationship between predictive factors and outcomes was assessed by using multiple binomial logistic regression. One hundred ninety-five teeth were extracted, resulting in 146 alveolar wounds, in which the majority (47%) consisted of alveolar sockets of multirooted teeth. One participant was diagnosed with SBP (Escherichia coli [E. coli]) and another diagnosed with bacterascites (Streptococcus viridans [S. viridans] group), occurring 11 and 6 days after tooth extraction. Poor soft tissue healing was observed in 20 (13.7%) patients, which was correlated to 2 risk factors, that is, jaundice (P = .007, adjusted odds ratio [OR] = 4.91, 95% confidence interval [CI] = 1.56-15.47) and moderate neutropenia (P = .048, adjusted OR = 13.99, 95% CI = 1.02-192.07). No association was found between tooth extraction and SBP in patients with cirrhosis. The delayed soft tissue healing was related to jaundice (hyperbilirubinemia) and moderate neutropenia.

Clinical characteristics and risk factors for bacterial co-infections in COVID-19 patients: A retrospective study

ObjectiveThis study aimed to analyse the bacterial composition, distribution, drug sensitivity, and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) who develop bacterial co-infections. MethodsWe conducted a retrospective study of 184 patients with COVID-19 admitted between December 2022 and January 2023. Data on gender, age, length of hospital stay, pneumonia classification, underlying diseases, invasive surgery, hormone therapy, inflammation indicators, and other relevant information were collected. Samples of sputum, bronchoscopy sputum, alveolar lavage fluid, middle urine, puncture fluid, wound secretions, and blood were collected for pathogen isolation, identification, and drug sensitivity testing. ResultsThe majority of patients with COVID-19 with bacterial co-infection were elderly and had underlying diseases. Invasive surgery and hormone therapy were identified as risk factors for co-infections. Laboratory analysis showed reduced lymphocyte counts and elevated levels of C-reactive protein and procalcitonin. The most common pathogens in co-infections were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The detection rate of drug-resistant strains, including methicillin-resistant S. aureus, carbapenem-resistant K. pneumoniae, carbapenem-resistant A. baumannii, carbapenem-resistant P. aeruginosa, and carbapenem-resistant E. coli, increased with the severity of pneumonia. ConclusionRespiratory tract infections were the most common site of bacterial co-infection in patients with COVID-19. Severe cases were more susceptible to multidrug-resistant pathogens, leading to a higher mortality rate. Timely control and prevention of co-infection are crucial for improving the prognosis of patients with COVID-19.

Recombinant GM-CSF for diseases of GM-CSF insufficiency: Correcting dysfunctional mononuclear phagocyte disorders.

Endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF), identified by its ability to support differentiation of hematopoietic cells into several types of myeloid cells, is now known to support maturation and maintain the metabolic capacity of mononuclear phagocytes including monocytes, macrophages, and dendritic cells. These cells sense and attack potential pathogens, present antigens to adaptive immune cells, and recruit other immune cells. Recombinant human (rhu) GM-CSF (e.g., sargramostim [glycosylated, yeast-derived rhu GM-CSF]) has immune modulating properties and can restore the normal function of mononuclear phagocytes rendered dysfunctional by deficient or insufficient endogenous GM-CSF. We reviewed the emerging biologic and cellular effects of GM-CSF. Experts in clinical disease areas caused by deficient or insufficient endogenous GM-CSF examined the role of GM-CSF in mononuclear phagocyte disorders including autoimmune pulmonary alveolar proteinosis (aPAP), diverse infections (including COVID-19), wound healing, and anti-cancer immune checkpoint inhibitor therapy. We discuss emerging data for GM-CSF biology including the positive effects on mitochondrial function and cell metabolism, augmentation of phagocytosis and efferocytosis, and immune cell modulation. We further address how giving exogenous rhu GM-CSF may control or treat mononuclear phagocyte dysfunction disorders caused or exacerbated by GM-CSF deficiency or insufficiency. We discuss how rhu GM-CSF may augment the anti-cancer effects of immune checkpoint inhibitor immunotherapy as well as ameliorate immune-related adverse events. We identify research gaps, opportunities, and the concept that rhu GM-CSF, by supporting and restoring the metabolic capacity and function of mononuclear phagocytes, can have significant therapeutic effects. rhu GM-CSF (e.g., sargramostim) might ameliorate multiple diseases of GM-CSF deficiency or insufficiency and address a high unmet medical need.

Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells.

Tissue damage, epithelial alterations, and intraepithelial presence of mast cells (MCs) are characteristics of asthma pathogenesis. Increased alveolar infiltration of MC populations has also been identified as a feature of asthma and other chronic respiratory diseases. The asthma associated receptor, urokinase plasminogen activator receptor (uPAR), has been shown to regulate bronchial epithelial repair responses. However, the impact of MC tryptase and chymase on functional properties and expression of uPAR in alveolar epithelial cells have not been fully investigated. Alveolar epithelial cell migration and wound healing were investigated using holographic live cell imaging of A549 cells in a wound scratch model post stimulation with tryptase or chymase. The expression of uPAR was investigated on the protein and gene level from cellular supernatants and in bronchoalveolar lavage fluid fractions from allergic asthmatics. We found that tryptase improved wound healing capacity, cellular migration and membrane bound uPAR expression. Chymase reduced gap closure capacity, cellular migration and membrane bound uPAR expression but increased soluble uPAR release. Our data suggest a dual regulatory response from the MC proteases in events related to uPAR expression and wound healing which could be important features in asthmatic disease.

Use of Chlorhexidine Bioadhesive Gel to Reduce Infection and Discomfort in Alveolar Bone Graft Wound: A Randomized Pilot Study

Use of Chlorhexidine Bioadhesive Gel to Reduce Infection and Discomfort in Alveolar Bone Graft Wound: A Randomized Pilot Study

Janus fibre/sponge composite combined with IOPNs promotes haemostasis and efficient reconstruction in oral guided bone regeneration

Placing a barrier membrane between an alveolar bone wound and gingival soft tissue is a common and effective method to prevent fibroblast invasion and promote new bone formation. However, the combined use of a barrier membrane with bone-forming substitutes remains a challenge for dentists during surgery. Thus, a Janus fibre/sponge composite combining iron oxide nanoparticles (IONPs, γ-Fe2O3) was fabricated to prevent epithelial invasion and promote alveolar reconstruction. In the scaffold, a poly (lactic-co-glycolic acid)/polycaprolactone (PP) electrospun layer was covalently bound with a chitosan sponge containing γ-Fe2O3 by polydopamine. The resilient chitosan sponge can easily adhere to the wound surface and encompass haemostatic capability by swelling and forming blood clots to block bleeding. The introduction of IONPs promoted the osteogenesis of rBMSCs, as shown by ALP analysis and cytokine assay. The PP layer maintained its structure integrity and prevented epithelial cells from invading into blood clots or fibroblasts from penetrating through the critical pore size. Assessment with a rat model having one-sided calvarial bone injury further confirmed the effectiveness of Janus scaffolds in facilitating the bone regeneration in the postoperative areas.

Ozone used as a supportive therapy for gingival tissue repair after facial trauma: Report of two cases

The application of ozone as a supportive therapy has been widely discussed. Ozone has antimicrobial, antioxidant, and healing properties. This study presents two cases of ozone application as a supportive therapy for gingival tissue repair after facial trauma. In both cases, patients suffered extensive lacerations with bone exposure. Tissues were repositioned and sutured; however, ischemia was observed during follow-up with potential tissue necrosis. Each patient received ozone gas with a concentration of 4 μg/ml. Then, the wound was irrigated with 40 mL of ozonated water at a final concentration of 8 μg/ml. The procedure was held weekly until clinical improvement. A significant improvement was observed in ischemia without evolution to necrosis or infection, allowing gingival tissue preservation. Ozone showed a beneficial effect in the recovery of gingiva and alveolar mucosa wounds after extensive trauma.

EFFICACY OF TWO DIFFERENT ANTIBIOTICS IN MANAGEMENT OF POST-OPERATIVE COMPLICATIONS OF IMPACTED THIRD MOLAR

Objective: To determine the efficacy of two different antibiotics in reducing the postoperative complications of impacted third molar. Materials and Methods: Total of 48 participants were included in this randomized control trial conducted in Feb 2019 to Feb 2020, which were divided into two groups by block randomization where group A was prescribed with amoxicillin while group B was prescribed with metronidazole. On 3rd and 7th post-operative day after the extraction pain was assessed using a 10mm visual analogue scale (VAS) while, maximum mouth opening was assessed using a Vernier caliper. Wound infection and alveolar osteitis were documented as dichotomous variable. Pain and mouth opening were evaluated using t-test or Mann-Whitney U test while alveolar osteitis and wound infections were compared using Chi-square and Fischer’s exact test. SPSS version 22 was used for analysis. P value <0.05 was taken as significant. Results: The results of individual groups revealed no difference in decreasing the postoperative complications after surgical extraction. There was no statistically significant difference between the groups in terms of mean age, VAS score and mouth opening at 3rd and 7th postoperative day (p>0.5). We found no significant association between antibiotics and incidence of wound infection and alveolar osteitis (p>0.5). Conclusion: Antibiotics have no significant role in reducing the postoperative pain, limited mouth opening, wound infection and alveolar osteitis. Hence, the use of antibiotic should be limited to surgeon’s choice.

Complications of Dentoalveolar Surgery

This article explores how to prevent and manage complications of dentoalveolar surgery. Many complications are avoidable. Surgical skills and knowledge of anatomy play an important role in prevention of complications. Prevention starts with detailed history and physical examination of the patient. Key to perioperative management of patients is risk assessment. Without a proper history and physical examination, the clinician is unable to assess the risk of performing surgery and anesthesia for each patient. Some illnesses and medications increase the risk of complications. The following complications are discussed: alveolar osteitis, displacement, fracture, hemorrhage, infection, nonhealing wound, oroantral communication, swelling, and trismus.

TRIM72 mediates lung epithelial cell death upon hyperoxia exposure.

Premature infants often require oxygen (O2) therapy for respiratory distress syndrome; however, excessive use of O2 can cause clinical conditions such as bronchopulmonary dysplasia. Although many treatment methods are currently available, they are not effective in preventing bronchopulmonary dysplasia. Herein, we explored the role of tripartite motif protein 72 (TRIM72), a factor involved in repairing alveolar epithelial wounds, in regulating alveolar cells upon hyperoxia exposure. In this in vivo study, we used Sprague-Dawley rat pups that were reared in room air or 85% O2 for 2 weeks after birth. The lungs were excised for histological analyses, and TRIM72 expression was assessed on postnatal days 7 and 14. For in vitro experiments, RLE-6TN cells (i.e., rat alveolar type II epithelial cells) and A549 cells (i.e., human lung carcinoma epithelial cells) were exposed to 85% O2 for 5 days. The cells were then analyzed for cell viability, and TRIM72 expression was determined. Exposure to hyperoxia reduced body and lung weight, increased mean linear intercept values, and upregulated TRIM72 expression. In vitro study results revealed increased or decreased lung cell viability upon hyperoxia exposure depending on the suppression or overexpression of TRIM72, respectively. Hyperoxia upregulates TRIM72 expression in neonatal rat lung tissue; moreover, it initiates TRIM72-dependent alveolar epithelial cell death, leading to hyperoxia-induced lung injury.

Surgical techniques for the removal of mandibular wisdom teeth.

Surgical techniques for the removal of mandibular wisdom teeth.

Vitamin C, a Key Factor in Post-extraction Healings A Preliminary Study

In clinical practice, after dental extraction, the main objective is the healing of the post-extraction wound, without complications and in the shortest time possible. According to specialized studies, the defense and regeneration mechanisms of the body are in direct correlation with the plasmatic level of some vitamins, mainly vitamin C, which is directly involved in the repair of damaged tissues. The purpose of the present study was to evaluate the healing of the post-extraction wound in the conditions of oral administration of vitamin C, according to a predetermined administration protocol, as compared to the healing process under conventional conditions. Five volunteers were included in the study, who presented two teeth with indication of extraction, one of the extractions being performed under the conditions of administration of vitamin C. The evolution of the healing of the post-extraction wounds was assessed comparatively. The examination was done with the help of photographic examination by directly measuring the vestibulo-oral dimensions of the wounds using the digital micrometer and by recording the blood microcirculation at the level of the alveolar wound using the laser Doppler flowmetry. The level of vitamin C in the tissues was also determined, using the lingual test for vitamin C, a simple and non-invasive method that uses the reagent 2.6 dichlorophenol-indophenol. The results of the preliminary study show that the evolution and healing of the post-extraction wound is accelerated under the conditions of vitamin C administration, with regard to the administration protocol used in the study and compared to the healing situation under classical conditions. It can be stated that the human body consumes higher amounts of ascorbic acid in the case of dental extractions therefore the administration of vitamin C is a necessity if a faster healing of their post-extraction wounds is desired.

Transcriptomic profiling reveals disease-specific characteristics of epithelial cells in idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is an incurable disease characterized by progressive lung fibrosis ultimately resulting in respiratory failure and death. Recurrent micro-injuries to the alveolar epithelium and aberrant alveolar wound healing with impaired re-epithelialization define the initial steps of the pathogenic trajectory. Failure of timely alveolar epithelial repair triggers hyper-proliferation of mesenchymal cells accompanied by increased deposition of extracellular matrix into the lung interstitium.MethodsWe previously isolated fibrosis-specific mesenchymal stem cell (MSC)-like cells from lung tissue of patients with interstitial lung diseases. These cells produced factors bearing anti-fibrotic potential and changed their morphology from mesenchymal to epithelial upon culture in an epithelial cell (EC)-specific growth medium. Here, we set out to molecularly characterize these MSC-like cell-derived ECs using global gene expression profiling by RNA-sequencing. Moreover, we aimed at characterizing disease-specific differences by comparing the transcriptomes of ECs from IPF and non-IPF sources.ResultsOur results suggest that differentially expressed genes are enriched for factors related to fibrosis, hypoxia, bacterial colonization and metabolism, thus reflecting many of the hallmark characteristics of pulmonary fibrosis. IPF-ECs showed enrichment of both pro- and anti-fibrotic genes, consistent with the notion of adaptive, compensatory regulation.ConclusionsOur findings support the hypothesis of a functional impairment of IPF-ECs, which could possibly explain the poor clinical outcome of IPF that roughly compares to those of advanced-stage cancers. Our study provides a valuable resource for downstream mechanistic investigation and the quest for novel therapeutic IPF targets.

Histological Study of Socket Healing after Tooth Extraction in Rabbits Treated with Short Term Diclofenac Sodium (Expermintal Study)

Aims: The aim of the present study is to investigate if short term therapy with diclofenac sodium of interferes with the time course of alveolar wound healing in rabbits. Materials and Methods: The sample included twelve rabbits; 6 rabbits received interamuscular injections of diclofenac sodium (10 mg/kg/day), one day before extraction, at a day of extraction and 4 days after extraction of the right mandibular incisors and 6 rabbits received interamuscular injections of normal saline. The animals were sacrificed in each group at 7, 14 and 21 days after tooth extraction. Results: The present results showed that the effect of diclofenac treatment caused no signifcant decrease in bone formation of socket healing. Conclusion: Histological study of short term therapy with diclofenac sodium after tooth extraction caused non-significant decrease in bone formation of extraction sockets healing in rabbits.

The receptor for advanced glycation end-products enhances lung epithelial wound repair: An in vitro study

Re-epithelialization of the alveolar surface is a key process of lung alveolar epithelial barrier repair after acute lung injury. The receptor for advanced glycation end-products (RAGE) pathway plays key roles in lung homeostasis, and its involvement in wound repair has been already reported in human bronchial epithelial cells. However, its effects on lung alveolar epithelial repair after injury remain unknown. We investigated whether RAGE stimulation with its ligands high–mobility group box 1 protein (HMGB1) or advanced glycation end-products (AGEs), alone or associated with RAGE inhibition using RAGE antagonist peptide, affects in vitro wound healing in human alveolar epithelial A549 cells. We further asked whether these effects could be associated with changes in cell proliferation and migration. We found that treatment of A549 cells with HMGB1 or AGEs promotes RAGE-dependent wound healing after a scratch assay. In addition, both RAGE ligands increased cell proliferation in a RAGE-dependent manner. Treatment with HMGB1 increased migration of alveolar epithelial cells at 12 h, independently of RAGE, whereas AGEs stimulated migration as measured 48 h after injury in a RAGE-dependent manner. Taken together, these results suggest that RAGE pathway is involved in lung alveolar epithelial wound repair, possibly through enhanced cell migration and proliferation.

Alveolar Epithelial Damage and Dysfunction as Common Features of Ischemia/Reperfusion Injury and Primary Graft Dysfunction in Lung Transplants

Ischemia reperfusion injury (I/R) is the major cause of primary graft dysfunction (PGD) after lung transplantation. I/R and PGD feature endothelial/alveolar epithelial damage, lung edema and inflammation. Edema resorption then depends on the restoration of alveolar epithelial integrity and the ability of alveolar cells to reabsorb Na+ (through ENaC channels) and fluid. We hypothesized that alveolar epithelial damage, and repair, are critical in PGD pathophysiology, and resolution. Therefore, our aim is to identify novel biomarkers and therapeutic targets associated with I/R using cellular and animal models as well as human samples from lung transplants. The impact of a protocol mimicking hypothermic ischemia and reperfusion was first tested on primary rat alveolar epithelial cell cultures. Then, an inflammatory stress was induced by LPS in a porcine model of ischemia/ex-vivo reperfusion. Finally, lung biopsies from the donor grafts were collected during lung transplantations and the PGD grade within the recipients were then determined. In primary alveolar cell cultures, we showed altered ENaC and tight junction protein (ZO-1) expression following the I/R mimicking protocol. A decline in transepithelial resistance and reduced alveolar wound repair rates were also observed. Treatment with a KvLQT1 K+ activator (R-L3) accelerated the repair rates and enhanced barrier integrity (ZO-1 staining) and ENaC protein expression. In the porcine model, alveolar damage, lung edema, exacerbated inflammatory response and decreased ENaC expression were observed after LPS-exposure. Preliminary data from lung transplant samples indicated an inflammatory response and decreased ENaC and ZO-1 expression in the donor graft among patients subsequently developing a PGD. Our data support the hypothesis of alveolar epithelial dysfunction after I/R injury. We will now investigate a potential relationship between donor phenotypic factors, markers of epithelial damage/dysfunctin within the grafts, inflammatory levels and the subsequent development of PGD in lung recipients.

Isotretinoina: Possível Interferência na Cicatrização Pós-Exodontia

Pharmacovigilance is defined as “the science and activities related to identification, evaluation, understanding and prevention of adverse effects or problems related to the use of drugs”. All drugs have both the potential to cause harm and benefit. 13-cis-Retinoic acid or isotretinoin is a reference anti-acne retinoid in the dermatological diseases treatment not responsive to conventional therapies, such as severe cystic acne. The drug-related side effects described in the medicine package insert imply changes in various human body systems. Those related to bone tissue, such as ligaments and tendons calcification, bone density reduction, epiphyseal closure and hypercalcemia, have great relevance for dentistry, raising the hypothesis of a possible interference in alveoli wound healing after extraction. This article aimed to conduct a literature review in gathering information about the possibility of isotretinoin interference in maxillofacial surgeries. In despite of the scarcity of conclusive scientific data about the influence of isotretinoin on human alveolar wound healing, recent studies on retinoid signaling pathways open new research perspectives for the isotretinoin interference on alveolar bone tissue. This possibility reinforces the importance of an isotretinoin drug-related side effects update, as well as a patients’ careful anamnesis with historical severe acne, in order to avoid complications.

Assessment of Predictive Biomarkers Associated with Ischemia/Reperfusion Injury and Primary Graft Dysfunction in Lung Transplants

Purpose Ischemia reperfusion (I/R) is a major cause of primary graft dysfunction (PGD) after lung transplantation. I/R and PGD feature endothelial/alveolar epithelial damage, lung edema and inflammation. Edema resorption depends on the restoration of alveolar integrity and its ability to reabsorb Na+ (ENaC) and fluid. We hypothesized that alveolar epithelial damage and repair are critical in PGD pathophysiology and resolution. Our aim is to identify novel markers and therapeutic targets associated with I/R using cellular and animal models as well as human samples from lung transplants. Methods Mimicking I/R protocol was used to evaluate alveolar epithelial barrier integrity and capacity of wound healing in primary cultures of rat's alveolar epithelial cells. These cell cultures were then treated with an activator of K+ channel (KvLQT1). In a porcine model of ischemia/ex-vivo reperfusion, an inflammatory stress was induced by i.v. infusion with LPS. Finally, samples were collected from 38 lung transplant patients. Results In primary cell cultures, we showed altered ENaC and tight junction protein (ZO-1) expression after injury. A decline in transepithelial resistance (TER) and altered alveolar wound repair rates were also observed following the mimicking I/R protocol. Treatment with K+ channel activator (R-L3) showed enhanced repair rates, barrier integrity (higher TER, ZO-1 staining) and ENaC expression. In our porcine model, lung damage and edema was observed as well as exacerbated inflammatory response and decreased ENaC expression. Preliminary data from lung transplant samples indicated an inflammatory response and decreased ENaC and ZO-1 expression in patients with PGD. Conclusion Our data support the hypothesis of alveolar epithelial dysfunction after I/R injury. We will now investigate a potential correlation between levels of inflammatory molecules and epithelial damage markers in bronchoalveolar lavages and blood samples (at different time-points) from lung transplants with various PGD scores.

Use of Transgingival Lag Screw Osteosynthesis in the Management of Alveolar Process Fracture.

The purpose of this study is to check the efficacy of transgingival lag screw osteosynthesis in alveolar process fractures of maxilla and mandible. A single-arm nonrandomized observational study was performed for the treatment of alveolar process fractures of maxilla and mandible. In this study, 20 mixed age group patients with alveolar process fracture were included. All the patients were treated by a 2.0-mm transgingival screw fixation under local or general anesthesia. All the patients were evaluated for fracture stability, anatomical reduction, bone loss and bone resorption of alveolar process, tooth loss, and wound infection at 3 months of follow-up. A simple descriptive statistical analysis was done to evaluate the parameters and it was shown that the treatment of alveolar process fracture with two or three lag screws provides adequate fracture stability and anatomical reduction with no signs of bone loss and tooth loss, and wound infections were noted post lag screw fixation. The study concludes that transgingival lag screw fixation is a suitable alternative for alveolar process fractures in all the age groups and two to three lag screws are generally sufficient to fix fractured alveolar process either under local anesthesia or general anesthesia.

Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-On-A-Chip.

The lung alveolar region experiences remodeling during several acute and chronic lung diseases, as for instance idiopathic pulmonary fibrosis (IPF), a fatal disease, whose onset is correlated with repetitive microinjuries to the lung alveolar epithelium and abnormal alveolar wound repair. Although a high degree of mechanical stress (>20% linear strain) is thought to potentially induce IPF, the effect of lower, physiological levels of strain (5–12% linear strain) on IPF pathophysiology remains unknown. In this study, we examined the influence of mechanical strain on alveolar epithelial wound healing. For this purpose, we adopted the “organ-on-a-chip” approach, which provides the possibility of reproducing unique aspects of the in vivo cellular microenvironment, in particular its dynamic nature. Our results provide the first demonstration that a wound healing assay can be performed on a breathing lung-on-a-chip equipped with an ultra-thin elastic membrane. We cultured lung alveolar epithelial cells to confluence, the cells were starved for 24 h, and then wounded by scratching with a standard micropipette tip. Wound healing was assessed after 24 h under different concentrations of recombinant human hepatic growth factor (rhHGF) and the application of cyclic mechanical stretch. Physiological cyclic mechanical stretch (10% linear strain, 0.2 Hz) significantly impaired the alveolar epithelial wound healing process relative to culture in static conditions. This impairment could be partially ameliorated by administration of rhHGF. This proof-of-concept study provides a way to study of more complex interactions, such as a co-culture with fibroblasts, endothelial cells, or immune cells, as well as the study of wound healing at an air–liquid interface.