Nanomaterial strategies in wound healing: A comprehensive review of nanoparticles, nanofibres and nanosheets.

Wound healing is a complex process that orchestrates the coordinated action of various cells, cytokines and growth factors. Nanotechnology offers exciting new possibilities for enhancing the healing process by providing novel materials and approaches to deliver bioactive molecules to the wound site. This article elucidates recent advancements in utilizing nanoparticles, nanofibres and nanosheets for wound healing. It comprehensively discusses the advantages and limitations of each of these materials, as well as their potential applications in various types of wounds. Each of these materials, despite sharing common properties, can exhibit distinct practical characteristics that render them particularly valuable for healing various types of wounds. In this review, our primary focus is to provide a comprehensive overview of the current state-of-the-art in applying nanoparticles, nanofibres, nanosheets and their combinations to wound healing, serving as a valuable resource to guide researchers in their appropriate utilization of these nanomaterials in wound-healing research. Further studies are necessary to gain insight into the application of this type of nanomaterials in clinical settings.

Turning sublimed sulfur and bFGF into a nanocomposite to accelerate wound healing via co-activate FGFR and Hippo signaling pathway.

Clinical treatment of diabetic refractory ulcers is impeded by chronic inflammation and cell dysfunction associated with wound healing. The significant clinical application of bFGF in wound healing is limited by its instability in vivo. Sulfur has been applied for the treatment of skin diseases in the clinic for antibiosis. We previously found that sulfur incorporation improves the ability of selenium nanoparticles to accelerate wound healing, yet the toxicity of selenium still poses a risk for its clinical application. To obtain materials with high pro-regeneration activity and low toxicity, we explored the mechanism by which selenium-sulfur nanoparticles aid in wound healing via RNA-Seq and designed a nanoparticle called Nano-S@bFGF, which was constructed from sulfur and bFGF. As expected, Nano-S@bFGF not only regenerated zebrafish tail fins and promoted skin wound healing but also promoted skin repair in diabetic mice with a profitable safety profile. Mechanistically, Nano-S@bFGF successfully coactivated the FGFR and Hippo signalling pathways to regulate wound healing. Briefly, the Nano-S@bFGF reported here provides an efficient and feasible method for the synthesis of bioactive nanosulfur and bFGF. In the long term, our results reinvigorated efforts to discover more peculiar unique biofunctions of sulfur and bFGF in a great variety of human diseases.

Targeting S100A12 to Improve Angiogenesis and Accelerate Diabetic Wound Healing.

Long-term inflammation and impaired angiogenesis are thought to be the causes of delayed healing or nonhealing of diabetic wounds. S100A12 is an essential pro-inflammatory factor involved in inflammatory reactions and serves as a biomarker for various inflammatory diseases. However, whether high level of S100A12 exists in and affects the healing of diabetic wounds, as well as the underlying molecular mechanisms, remain unclear. In this study, we found that the serum concentration of S100A12 is significantly elevated in patients with type 2 diabetes. Exposure of stratified epidermal cells to high glucose environment led to increased expression and secretion of S100A12, resulting in impaired endothelial function by binding to the advanced glycation endproducts (RAGE) or Toll-like receptor 4 (TLR4) on endothelial cell. The transcription factor Krüpple-like Factor 5 (KLF5) is highly expressed in the epidermis under high glucose conditions, activating the transcriptional activity of the S100A12 and boost its expression. By establishing diabetic wounds model in alloxan-induced diabetic rabbit, we found that local inhibition of S100A12 significantly accelerated diabetic wound healing by promoting angiogenesis. Our results illustrated the novel endothelial-specific injury function of S100A12 in diabetic wounds and suggest that S100A12 is a potential target for the treatment of diabetic wounds.

A carrier-free, injectable, and self-assembling hydrogel based on carvacrol and glycyrrhizin exhibits high antibacterial activity and enhances healing of MRSA-infected wounds.

Inspired by glycyrrhizin's strong pharmacological activities and the directed self-assembly into hydrogels, we created a novel carrier-free, injectable hydrogel (CAR@glycygel) by combining glycyrrhizin with carvacrol (CAR), without any other chemical crosslinkers, to promote wound healing on bacteria-infected skin. CAR appeared to readily dissolve and load into CAR@glycygel. CAR@glycygel had a dense, porous, sponge structure and strong antioxidant characteristics. In vitro, it showed better antibacterial ability than free CAR. For methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Escherichia coli, the diameter of inhibition zone values of CAR@glycygel were 3.80 ± 0.04, 3.31 ± 0.20 and 3.12 ± 0.24 times greater, respectively, than those of free CAR. The MICs for CAR@glycygel was 156.25 µg/mL while it was 1250.00 µg/mL for free CAR to these three bacteria. Its antibacterial mechanism appeared to involve destruction of the integrity of the bacterial cell wall and biomembrane, leading to a leakage of AKP and inhibition of biofilm formation. In vivo, CAR@glycygel effectively stopped bleeding. When applied to skin wounds on rats infected with MRSA, CAR@glycygel had strong bactericidal activity and improved wound healing. The wound healing rates for CAR@glycygel were 49.59 ± 15.78 %, 93.02 ± 3.09 % and 99.02 ± 0.55 % on day 3, day 7, and day 11, respectively, which were much better than blank control and positive control groups. Mechanisms of CAR@glycygel accelerating wound healing involved facilitating epidermis remolding, promoting the growth of hair follicles, stimulating collagen deposition, mitigating inflammation, and promoting angiogenesis. Overall, CAR@glycygel showed great potential as wound dressing for infected skin wounds.

The utilization of chitosan/Bletilla striata hydrogels to elevate anti-adhesion, anti-inflammatory and pro-angiogenesis properties of polypropylene mesh in abdominal wall repair.

Polypropylene (PP) mesh is commonly used in abdominal wall repair due to its ability to reduce the risk of organ damage, infections and other complications. However, the PP mesh often leads to adhesion formation and does not promote functional tissue repair. In this study, we synthesized one kind of aldehyde Bletilla striata polysaccharide (BSPA) modified chitosan (CS) hydrogel based on Schiff base reaction. The hydrogel exhibited a porous network structure, a highly hydrophilic surface and good biocompatibility. We wrapped the PP mesh inside the hydrogel and evaluated the performance of the resulting composites in a bilateral 1 × 1.5 cm abdominal wall defect model in rats. The results of gross observation, histological staining and immunohistochemical staining demonstrated the positive impact of the CS hydrogel on anti-adhesion and wound healing effects. Notably, the addition of BSPA to the CS hydrogel further improved the performance of the composites in vivo, promoting wound healing by enhancing collagen deposition and capillary rearrangement. This study suggested that the BSPA-modified CS hydrogel significantly promoted the anti-adhesion, anti-inflammatory and pro-angiogenesis properties of PP meshes during the healing process. Overall, this work offers a novel approach to the design of abdominal wall repair patches.

Outcomes in Patients with Heel Ulcerations that Underwent Below the Knee Amputations versus Vertical Contour Calcanectomy: Importance of Selection Criteria.

The aim of the study was to compare preoperative factors and postoperative outcomes in patients with heel ulcerations that primarily had a transtibial (below the knee) amputation (N=38) versus vertical contour calcanectomy (n=62). The groups had no statistical difference between their Charlson Comorbidity Index Score, a prognostic score of ten-year survival in patients with multiple comorbidities. The odds of primary closure was 21.1 times higher in patients that underwent below knee amputation compared to patients that underwent vertical contour calcanectomy [OR 21.1 (95% CI 3.89-114.21)]. The odds of positive soft tissue culture at time of closure were 17.1 times higher for patients that underwent vertical contour calcanectomy [OR 17.1 (95% CI 5.40-54.16)]. The odds of a patent posterior tibial artery was 3.3 times higher for patients that underwent vertical contour calcanectomy [OR 3.3 (95% 1.09-10.09)]. The secondary aim of the study was to evaluate preoperative factors and postoperative outcomes in patients with failed vertical contour calcanectomy, defined as needing a below knee amputation. The odds of vertical contour calcanectomy failure was 13.7 times higher in male patients [OR 13.7 (95% CI 1.80-107.60)]. Vertical contour calcanectomy failure was 5.7 times higher in patients with renal disease [OR 5.7 (95% CI 1.10-30.30)], and vertical contour calcanectomy failure was 16.1 times higher for patients who needed additional surgery post closure [OR 16.1 (95% CI 1.40-183.20)].

Maggot therapy for resistant infections: the disconnect between scientific evidence, clinical acceptance and practice.

OBJECTIVE: Practitioners and scientists are re-examining marginalised wound care therapies to find strategies that combat the growing problem of antimicrobial resistance (AMR) without compromising patient outcomes. Maggot therapy (MT) makes up just an estimated 0.02% of UK's National Health Service spending on wound care. This study aims to uncover why MT is not used more often, despite its affordability and high level of efficacy for both debridement and disinfection, particularly in the context of AMR infections, and to determine what can be done to ensure MT is more effectively used in the future to improve patient outcomes and manage the growing problem of AMR. METHOD: For this investigation, a qualitative review of case studies using MT against AMR infections and a quantitative analysis of randomised control trials (RCTs) were performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. RESULTS: Analysis showed that MT is highly effective against a range of infections and wound types, and compares well against conventional therapies. The low use of MT may be due in part to the documented 'yuck factor', often associated with maggots as well as misconceptions around the cost, efficacy and accessibility of MT. To overcome these factors, more RCTs on the spectrum and efficacy of MT across various clinical manifestations are needed, as well as professional and public engagement campaigns. CONCLUSION: MT is an underused therapy, particularly regarding AMR infections, and expanding its use in these circumstances appears warranted. MT could play a vital role in conserving the efficacy of the existing pool of antimicrobials available and should be considered in the development of antimicrobial stewardship programmes. DECLARATION OF INTEREST: This work was supported by the Swansea Employability Academy, Swansea University (internal funding). The authors have no conflicts of interest to declare.

Management of a complicated colonexposed sacrococcygeal wound after pelvic exenteration: a case report.

DECLARATION OF INTEREST: This work was supported by the Naval Medical University and the University of Shanghai for Science and Technology Joint Projects (2020-RZ04), the Innovative Clinical Research Program of Shanghai Changzheng Hospital (2020YLCYJ-Y16), and the academic project of Naval Medical University (2022QN073). The authors have no conflicts of interest to declare.

Efficacy of autologous platelet-rich plasma gel in patients with hard-to-heal diabetic foot ulcers: a multicentre study in Japan.

OBJECTIVE: To evaluate the healing outcome of a platelet-rich plasma (PRP) gel prepared using TKKT01 (a wound care device to prepare the PRP gel) in patients with hard-to-heal diabetic foot ulcers (DFUs) and who showed an inadequate response to ≥4 weeks of standard of care (SoC). METHOD: This open-label, single-arm, multicentre study was conducted in 15 centres in Japan. Eligible patients received PRP gel treatment twice a week for eight weeks, followed by a final evaluation after the completion of week 8 (day 57). The primary endpoint was the percentage of patients who achieved ≥50% reduction in wound radius at the final evaluation (achievement criterion, ≥60% of patients). Secondary endpoints included: wound area and volume reduction rates; time to possible wound closure by secondary intention; time to possible wound closure using a relatively simple procedure (e.g., skin graft and suture); and safety at the final evaluation. RESULTS: A total of 54 patients were included in the full analysis set, with 47 patients included in the per protocol set; the primary endpoint was met in 38/47 (80.9%) (95% confidence interval: 66.7-90.9%) patients who achieved ≥50% wound radius reduction at the final evaluation. High rates of wound area (72.8%) and volume (92.7%) reduction were observed at the final evaluation. The median time to possible wound closure by secondary intention and by use of a relatively simple procedure was 57 and 43 days, respectively. Complete wound closure at the final evaluation was achieved in 27 (57.4%) patients. No safety concerns were raised. CONCLUSION: In this study, the efficacy and safety of PRP gel treatment with TKKT01 in patients with hard-to-heal DFUs in Japan were confirmed by our findings. DECLARATION OF INTEREST: This study was funded by Rohto Pharmaceutical Co., Ltd., Japan. NO has been paid a consulting fee by Rohto Pharmaceutical Co., Ltd. KH is the Chief Medical Officer of Rohto Pharmaceutical. Co., Ltd. The other authors have no conflict of interest to declare.

The influence of socioeconomic factors on intervention and postoperative healing of venous ulcers: a prospective study.

OBJECTIVE: In previous studies, venous ulcers (VUs) have been found to occur more often in patients with lower socioeconomic status. The aim of this study was to explore if socioeconomic factors influence the delay of referral to a vascular service or the time to healing after superficial venous intervention. METHOD: In this prospective study, patients answered a questionnaire about the duration and recurrence of their VU, comorbidities, body mass index (BMI), smoking, alcohol, social and physical activities, ambulatory status, education, marital status, housing, perceived economic status and dependence on home care. Postoperative complications, VU healing and recurrence were noted one year after superficial venous intervention. RESULTS: A total of 63 patients were included in this study (30 females and 33 males), with a mean age of 71.2 years (range: 37-92 years). Duration of the present VU in patients was: <3 months in 48%; 3-6 months in 27%; 6-12 months in 11%; and >12 months in 14%. Risk factors for delayed referral were recurrent VU (odds ratio (OR): 4.92; p=0.021); walking impairment (OR: 5.43; p=0.009) and dependence on home care (OR: 4.89: p=0.039) in a univariable analysis. The latter was the only significant finding in a multivariable analysis with socioeconomic risk factor (OR: 4.89; p=0.035). In 85% of patients, their VU healed without recurrence during one year follow-up. Healing took longer if the patients: were of older age (p=0.033); had a normal BMI (independent samples t-test, p=0.028); had a recurrent VU (OR: 5.00; p=0.049); or walking impairment (Fishers exact test, OR: 9.14; p=0.008), but no significant socioeconomic risk factors were found. CONCLUSION: In this study, socioeconomic factors were not important risk factors for delayed referral of VU patients to a vascular service or prolonged healing time after superficial venous intervention. DECLARATION OF INTEREST: This work was supported by the Scandinavian Research Foundation for Varicose Veins and other Venous Diseases (SFÅV) and by ALF funding from Region Örebro County. The authors have no conflicts of interest to declare.

Performance of a gelling fibre dressing in management of wounds in a community setting: a sub-analysis of the VIPES study.

OBJECTIVE: To evaluate the use and performance of a gelling fibre dressing (Biatain Fiber; Coloplast A/S, Denmark) in the management of wounds in community nursing practice. METHOD: A sub-analysis of the prospective, observational, real-world VIPES (Observatoire en Ville des Plaies ExSudatives) study was conducted. Patients with exuding wounds, for which nurses chose to apply the gelling fibre as a primary dressing, were included. Outcomes included assessments of wound condition and patient/nurse opinion. RESULTS: Overall, 149 patients with acute (n=52; 34.9%) or hard-to-heal (chronic) (n=97; 65.1%) wounds were included. At baseline, mean±standard deviation wound age was 351.5±998.2 days, 108 (72.5%) wounds were moderately-to-highly exuding, and 126 (84.6%) showed exudate pooling in the wound bed. At the last follow-up visit, 29 (19.5%) wounds had healed, within a median of 36 days, and 64 (43.0%) were progressing towards healing. From baseline to the last follow-up visit, significant reductions in wound surface area (p<0.05), depth (p<0.01), exudate level (p<0.0001), and in the proportion of wounds with sloughy tissue (p<0.0001) were observed. Most wounds had no (n=86; 58.5% (two missing values)) or low exudate pooling (n=45; 30.6% (two missing values)) at the last visit and proportions of patients with healthy wound edges/periwound skin increased from baseline. At the last visit, wounds were considered improved by nurses in 71.4% (n=105) of cases, and by patients in 66.7% (n=98) of cases (two patients missing). CONCLUSION: Patients who received treatment with the gelling fibre experienced improvements in the condition of a range of complex wounds. This analysis highlights the importance of adequate exudate management, and indicates how the selection of an appropriate wound dressing can encourage healing progression. DECLARATION OF INTEREST: This study was financially supported by Laboratoires Coloplast SAS, Paris, France. Coloplast A/S funded the writing and editing of the article and contributed to its content. Coloplast A/S and Laboratoires Coloplast SAS reviewed the article for scientific accuracy. Nurses received financial compensation for their participation in the study. NA is a full-time employee of Coloplast A/S. APJ was an employee of Coloplast A/S when this article was written. FA was a full-time employee of Laboratoires Coloplast SAS at the time of publication development. RS and CJ are full-time employees of CEN Biotech. AK received an educational grant from Coloplast A/S to provide scientific input to the publication. The authors have no other conflicts of interest to declare.

Wellbeing, quality of life and satisfaction of patients with hard-to-heal wounds: a descriptive study.

OBJECTIVE: A hard-to-heal wound is defined as a wound that failed to proceed through the normal phases of wound healing in an orderly and timely manner. The purpose of this article is to describe the impact of hard-to-heal wounds on the wellbeing, quality of life (QoL) and satisfaction with QoL of patients in Oman with hard-to-heal wounds. METHOD: A descriptive cross-sectional study of patients with hard-to-heal wounds attending three tertiary care hospitals using a self-reported questionnaire was conducted. RESULTS: A total of 275 patients took part in the study. Patients reported a low wellbeing score (67.06±19.72), moderate QoL score (52.18±25.07) and moderate satisfaction scores (68.91±23.88). Significant mean differences were reported with age, sex, educational level, monthly income and type of wound all at p<0.05. CONCLUSION: The findings of this study demonstrated that hard-to-heal wounds could influence the wellbeing, QoL and overall satisfaction with QoL of patients. DECLARATION OF INTEREST: Funding was received through an internal grant of the Sultan Qaboos University to conduct the research conducting the research (IG/CON/FACN/20/01). The authors have no conflicts of interest to declare.

Correlation of ankle-wrist pressure index with ankle-brachial pressure index to assess lower limb perfusion in diabetic foot ulcer: a pilot study.

OBJECTIVE: The presence of peripheral artery disease (PAD) in patients with diabetic foot ulcers (DFUs) is a significant risk factor for chronicity and amputation. Ankle-brachial pressure index (ABPI) is a screening tool for PAD. Brachial systolic pressure measurement, used as a denominator in the calculation of ABPI, produces inaccurate results in patients with obesity and the presence of heavy clothing. The wrist, however, is easily accessible, and the ankle-wrist pressure index (AWPI), if comparable with ABPI, may be useful in screening selected patients. This study aimed to assess the efficacy of AWPI in diagnosing perfusion in DFUs and compare it to ABPI in patients with DFUs. METHOD: ABPI and AWPI were calculated by measuring systolic blood pressure in the arteries of the ankle, arm and wrist with a handheld Doppler. Actual perfusion was determined by the presence or absence of PAD by duplex ultrasound. RESULTS: A total of 46 lower extremities in 41 patients were studied. The prevalence of PAD was 61%. Duplex ultrasound confirmed that the sensitivity of ABPI and AWPI in detecting PAD in patients with DFUs was 67.9% and 71.4% respectively, whereas the specificity of ABPI and AWPI was 94.4% and 88.9% respectively. On receiver operating characteristic analysis, the area under the curve of ABPI and AWPI was 0.804 and 0.795, respectively. A statistically significant positive correlation between ABPI and AWPI was found (r=0.986; p<0.001). CONCLUSION: There was a good correlation between ABPI and AWPI over a wide range of values. ABPI and AWPI may have a similar role in predicting perfusion in patients with DFUs. AWPI could be used in place of ABPI in selected patients in whom measuring ABPI may be difficult. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare.

Incidence of medical adhesive-related skin injury: a reduction by changing posture.

OBJECTIVE: Medical adhesive-related skin injuries (MARSI), defined as skin damage associated with the use of medical adhesive products or devices, are a common and under-reported condition that compromises skin integrity. The prevention and management of MARSI that can occur around the needle insertion site of a chest wall implantable port in hospitalised patients with a tumour remain challenging issues. The aim of this study was to explore whether the incidence of MARSI could be reduced by changing the body position during dressing changes. METHOD: Participants were recruited between May 2019 and November 2020 in the oncology department of a tertiary hospital. Patients were randomly assigned to Group AB (supine followed by semi-recumbent position) and Group BA (semi-recumbent followed by supine position) with a standard intervening recovery interval of 21-28 days. Assessments for typical MARSI included itching, the combination of erythema and oedema, and blisters in the port area, and were graded according to the level of severity. RESULTS: The itch intensity was significantly lower in phase B (semi-recumbent) compared to phase A (supine) (2.35±1.985 versus 5.31±1.332, respectively; p<0.01). Similarly, the severity of erythema and oedema was less severe when comparing phase B to phase A: grade 0 (64.9% versus 10.5%, respectively); grade 1 (28.1% versus 19.3%, respectively); grade 2 (3.5% versus 7.0%, respectively); grade 3 (1.8% versus 45.6%, respectively); and grade 4 (1.8% versus 17.5%, respectively) (Z=5.703; p<0.01). Blisters were found far less frequently in phase B than phase A (1.8% versus 56.1%, respectively; p<0.01). CONCLUSION: The study provided statistically significant evidence that patients in a semi-recumbent position receiving dressing at a chest wall implantable port had fewer and less severe injection site MARSI than when in a supine position. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare.

Exosomes derived from cord blood Treg cells promote diabetic wound healing by targeting monocytes.

Chronic nonhealing diabetic wounds are a critical clinical challenge. Regulatory T cells (Tregs) are immunosuppressive modulators affecting wound healing progression by controlling the inflammatory response. The current study attempted to investigate whether the exosomes derived from cord blood (CB) Tregs can accelerate the healing process. Exosomes were isolated from CB-Treg cultures using ultracentrifugation and validated with different specific markers of exosomes. The purified CB-Treg-derived exosomes were co-cultured with peripheral blood mononuclear cells (PBMCs) and CD14+ monocytes. The migration-promoting effect of CB-Treg-derived exosomes on fibroblasts and endothelial cells was investigated. We used thermosensitive Pluronic F-127 hydrogel (PF-127) loaded with CB-Treg-derived exosomes in a diabetic wound healing mouse model. CB-Treg-derived exosomes with 30-120 nm diameters revealed exosome-specific markers, such as TSG101, Alix, and CD63. CB-Treg-derived exosomes were mainly bound to the monocytes when co-cultured with PBMCs, and promoted monocyte polarization to the anti-inflammatory phenotype (M2) in vitro. CB-Treg-derived exosomes enhanced the migration of endothelial cells and fibroblasts. Furthermore, CB-Treg-derived exosomes treatment accelerated wound healing by downregulating inflammatory factor levels and upregulating the M2 macrophage ratio in vivo. Our findings indicated that CB-Treg-derived exosomes could be a promising cell-free therapeutic strategy for diabetic wound healing, partly by targeting monocytes.

In-vitro and in-vivo investigation of wound healing efficacy of Syzygium cumini leaf extracts loaded carboxymethylcellulose film.

The study focused on Syzygium cumini Leaf Extract (SCLE) loaded into Carboxymethylcellulose (CMC) film via Solution casting. Phytochemical screening revealed carbohydrates, and HPLC analysis identified quercetin, known for promoting wound healing. FT-IR spectroscopy confirmed various functional groups. X-Ray diffraction (XRD) determined the crystallite size to be 14.58 nm. Field Emission Scanning Electron Microscopy (FESEM) showed the dispersion of extracts, and Energy Dispersive X-ray (EDX) analysis detailed the weight percentages of components. Antibacterial activity tests revealed zones of inhibition for S. aureus (15 mm) and E. coli (11 mm). The film exhibited 63.11 % antioxidant activity at 517 nm with DPPH at a 750 µL sample concentration. Drug release kinetics were also studied. In-vitro wound healing using the L929 cell line showed 83 % healing at a 100 µL concentration. Over 14 days, the treatment group's wounds healed completely within 7 days, unlike the control groups which showed no recovery after 14 days. These findings indicate that the SCLE-CMC film is highly effective in promoting wound healing.

Modeling the mechanosensitive collective migration of cells on the surface and the interior of morphing soft tissues.

Cellular contractility, migration, and extracellular matrix (ECM) mechanics are critical for a wide range of biological processes including embryonic development, wound healing, tissue morphogenesis, and regeneration. Even though the distinct response of cells near the tissue periphery has been previously observed in cell-laden microtissues, including faster kinetics and more prominent cell-ECM interactions, there are currently no models that can fully combine coupled surface and bulk mechanics and kinetics to recapitulate the morphogenic response of these constructs. Mailand et al. (Biophys J 117(5):975-986, 2019) had shown the importance of active elastocapillarity in cell-laden microtissues, but modeling the distinct mechanosensitive migration of cells on the periphery and the interior of highly deforming tissues has not been possible thus far, especially in the presence of active elastocapillary effects. This paper presents a framework for understanding the interplay between cellular contractility, migration, and ECM mechanics in dynamically morphing soft tissues accounting for distinct cellular responses in the bulk and the surface of tissues. The major novelty of this approach is that it enables modeling the distinct migratory and contractile response of cells residing on the tissue surface and the bulk, where concurrently the morphing soft tissues undergo large deformations driven by cell contractility. Additionally, the simulation results capture the changes in shape and cell concentration for wounded and intact microtissues, enabling the interpretation of experimental data. The numerical procedure that accounts for mechanosensitive stress generation, large deformations, diffusive migration in the bulk and a distinct mechanism for diffusive migration on deforming surfaces is inspired from recent work on bulk and surface poroelasticity of hydrogels involving elastocapillary effects, but in this work, a two-field weak form is proposed and is able to alleviate numerical instabilities that were observed in the original method that utilized a three-field mixed finite element formulation.

A Highly Stable, Multifunctional Janus Dressing for Treating Infected Wounds.

The limited and unstable absorption of excess exudate is a major challenge during the healing of infected wounds. In this study, a highly stable, multifunctional Janus dressing with unidirectional exudate transfer capacity is fabricated based on a single poly(lactide caprolactone) (PLCL). The success of this method relies on an acid hydrolysis reaction that transforms PLCL fibers from hydrophobic to hydrophilic in situ. The resulting interfacial affinity between the hydrophilic/phobic PLCL fibers endows the Janus structure with excellent unidirectional liquid transfer and high structural stability against repeated stretching, bending, and twisting. Various other functions, including wound status detection, antibacterial, antioxidant, and anti-inflammatory properties, are also integrated into the dressing by incorporating phenol red and epigallocatechin gallate. An in vivo methicillin-resistant Staphylococcus aureus-infected wound model confirms that the Janus dressing, with the capability to remove exudate from the infected site, not only facilitates epithelialization and collagen deposition, but also ensures low inflammation and high angiogenesis, thus reaching an ideal closure rate up to 98.4% on day 14. The simple structure, multiple functions, and easy fabrication of the dressing may offer a promising strategy for treating chronic wounds, rooted in the challenges of bacterial infection, excessive exudate, and persistent inflammation.

Preclinical Therapeutic Efficacy of Extracellular Vesicles Derived from Adipose-Derived Mesenchymal Stromal/Stem Cells in Diabetic Wounds: a Systematic Review and Meta-Analysis.

Extracellular vesicles isolated from adipose tissue-derived mesenchymal stromal/stem cells (ADSC-EVs) have demonstrated promising potential in wound healing treatment. To determine the therapeutic efficacy of ADSC-EVs for diabetic wounds in preclinical models, we performed a meta-analysis of available studies. PubMed and Embase were searched (to April 23, 2023). All full-text articles describing the therapeutic application of ADSC-EVs in diabetic wounds were included. Study outcomes were pooled using a random effects meta-analysis, including wound closure, angiogenesis, and collagen deposition. Other outcomes were only discussed descriptively. Seventy unique records were identified from our search; 20 full-text articles were included for qualitative analysis. Twelve studies were eligible for quantitative meta-analysis. The results showed that ADSC-EVs accelerated diabetic wound healing compared to controls with a large effect (standardized mean difference (SMD) 4.22, 95% confidence interval (CI) 3.07 to 5.36). The administration of ADSC-EVs also improved neovascularization (SMD 9.27, 95% CI 4.70 to 13.83) and collagen deposition (SMD 2.19, 95% CI 0.94 to 3.44), with a large effect. The risk of bias was unclear in all included studies. Conclusively, ADSC-EV is an effective treatment for diabetic wounds in preclinical trials, and it appears justified for transfer into the clinical field.