Feasibility of intra-operative image guidance in burn excision surgery with multispectral imaging and deep learning.

BACKGROUND: Exposing a healthy wound bed for skin grafting is an important step during burn surgery to ensure graft take and maintain good functional outcomes. Currently, the removal of non-viable tissue in the burn wound bed during excision is determined by expert clinician judgment. Using a porcine model of tangential burn excision, we investigated the effectiveness of an intraoperative multispectral imaging device combined with artificial intelligence to aid clinician judgment for the excision of non-viable tissue. METHODS: Multispectral imaging data was obtained from serial tangential excisions of thermal burn injuries and used to train a deep learning algorithm to identify the presence and location of non-viable tissue in the wound bed. Following algorithm development, we studied the ability of two surgeons to estimate wound bed viability, both unaided and aided by the imaging device. RESULTS: The deep learning algorithm was 87% accurate in identifying the viability of a burn wound bed. When paired with the surgeons, this device significantly improved their abilities to determine the viability of the wound bed by 25% (p = 0.03). Each time a surgeon changed their decision after seeing the AI model output, it was always a change from an incorrect decision to excise more tissue to a correct decision to stop excision. CONCLUSION: This study provides insight into the feasibility of image-guided burn excision, its effect on surgeon decision making, and suggests further investigation of a real-time imaging system for burn surgery could reduce over-excision of burn wounds.

Maximizing wound coverage in full-thickness skin defects: A randomized-controlled trial of autologous skin cell suspension and widely meshed autograft versus standard autografting.

BACKGROUND: Traumatic insults, infection, and surgical procedures can leave skin defects that are not amenable to primary closure. Split-thickness skin grafting (STSG) is frequently used to achieve closure of these wounds. Although effective, STSG can be associated with donor site morbidity, compounding the burden of illness in patients undergoing soft tissue reconstruction procedures. With an expansion ratio of 1:80, autologous skin cell suspension (ASCS) has been demonstrated to significantly decrease donor skin requirements compared with traditional STSG in burn injuries. We hypothesized that the clinical performance of ASCS would be similar for soft tissue reconstruction of nonburn wounds. METHODS: A multicenter, within-patient, evaluator-blinded, randomized-controlled trial was conducted of 65 patients with acute, nonthermal, full-thickness skin defects requiring autografting. For each patient, two treatment areas were randomly assigned to concurrently receive a predefined standard-of-care meshed STSG (control) or ASCS + more widely meshed STSG (ASCS+STSG). Coprimary endpoints were noninferiority of ASCS+STSG for complete treatment area closure by Week 8, and superiority for relative reduction in donor skin area. RESULTS: At 8 weeks, complete closure was observed for 58% of control areas compared with 65% of ASCS+STSG areas (p = 0.005), establishing noninferiority of ASCS+STSG. On average, 27.4% less donor skin was required with ASCS+ STSG, establishing superiority over control (p < 0.001). Clinical healing (≥95% reepithelialization) was achieved in 87% and 85% of Control and ASCS+STSG areas, respectively, at 8 weeks. The treatment approaches had similar long-term scarring outcomes and safety profiles, with no unanticipated events and no serious ASCS device-related events. CONCLUSION: ASCS+STSG represents a clinically effective and safe solution to reduce the amount of skin required to achieve definitive closure of full-thickness defects without compromising healing, scarring, or safety outcomes. This can lead to reduced donor site morbidity and potentially decreased cost associated with patient care.Clincaltrials.gov identifier: NCT04091672. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level I.

Multicellular bioprinted skin facilitates human-like skin architecture in vivo.

Bioprinting is a promising alternative method to generate skin substitutes because it can replicate the structural organization of the skin into biomimetic layers in vitro. In this study, six primary human skin cell types were used to bioprint a trilayer skin construct consisting of epidermis, dermis, and hypodermis. Transplantation of the bioprinted skin with human cells onto full-thickness wounds of nu/nu mice promoted rapid vascularization and formation of epidermal rete ridges analogous to the native human epidermis, with a normal-looking extracellular matrix. Cell-specific staining confirmed the integration of the implanted cells into the regenerated skin. Using a similar approach, a 5 centimeter-by-5 centimeter bioprinted autologous porcine skin graft was transplanted onto full-thickness wounds in a porcine excisional wound model. The bioprinted skin graft improved epithelialization, reduced skin contraction, and supported normal collagen organization with reduced fibrosis. Differential gene expression demonstrated pro-remodeling protease activity in wounds transplanted with bioprinted autologous skin grafts. These results demonstrate that bioprinted skin can support skin regeneration to allow for nonfibrotic wound healing and suggest that the skin bioprinting technology may be applicable for human clinical use.

Effectiveness of Home Gardening in Improving Food Security and Health in Chacraseca, Nicaragua: A Pilot Study.

We studied the usefulness of home gardening in improving food security and health. One hundred participants were randomized into the control and intervention group of which the intervention group received training in home gardening. Results showed that the percentage of participants with normal body mass index decreased from 24.4% to 20% in the control group whereas it remained unchanged in the intervention group. The number of participants in the very low food security category decreased from 66% (n=33) to 54% (n=27) in the intervention group whereas it increased from 68.8% (n=33) to 70.8% (n=34) in the control group. Results from the present study may be used to guide policymakers in designing or modifying home gardening interventions.

ARAG, an Antioxidant-Rich Gel, Shows Superiority to Mepilex Ag in the Treatment of Deep Partial Thickness Burns without Sacrificing Antimicrobial Efficiency.

Current treatments for deep tissue burns are limited, and most serve only to enhance hydration or prevent bacterial growth. This leaves burn healing dependent on slow natural processes to debride the wound and reestablish the epidermal and dermal layers of the skin. Infections are well known to destabilize this process through a variety of mechanisms, most notably through increased inflammation and the resulting oxidative stress. In this study, we show that ARAG (an antioxidant-rich antimicrobial gel) can suppress the growth of multiple bacteria commonly found to infect burns (Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, and Staphylococcus aureus). This inhibition is comparable to that conferred by silver ion release from burn dressings such as Mepilex-Ag. We further show, using a porcine model for deep partial-thickness burns, that ARAG allows for enhanced wound healing over Mepilex-Ag, the current standard of care. Histological findings indicate this is likely due to increased wound debridement and dampening of late inflammatory processes, leading to more balanced physiologic healing. Taken together, these findings show promise for ARAG as a superior alternative to the current standard of care.

Examining albumin as a bioindicator of healing capability in patients with diabetic foot ulcers: a retrospective review.

INTRODUCTION: Identifying a bioindicator of healing capacity would be beneficial in guiding treatment of and reducing morbidity in patients with DFU. Hypoalbuminemia is a well-established risk factor for amputation and, thus, a promising candidate. OBJECTIVE: This study was conducted to examine whether albumin values over a 12-week treatment course for DFU correlated with ulcer size and outcomes. MATERIALS AND METHODS: A retrospective review was conducted of 793 patients who presented to the Atrium Health Wake Forest Baptist Wound Care and Hyperbaric Center between 2010 and 2022. Sixty-two patients met the inclusion criteria. Albumin values and wound size data were collected monthly over a 12-week treatment course. RESULTS: Initial albumin values were not significantly different between patients healed by 12 weeks compared with nonhealed patients. Healed proportion and average initial ulcer size in patients with at least 1 hypoalbuminemia value (<3.0 g/dL) were not significantly different from those in patients with normal albumin levels. Patients who trended from normoalbuminemia to hypoalbuminemia displayed significantly increased wound sizes compared to patients with albumin changes within the normal range (0.04 cm² and -1.17 cm², respectively; P < .05). Monthly changes in albumin correlated poorly with wound healing (r = 0.144, P = .240), and large negative albumin trends (>0.5 g/dL per month) did not correlate with increased wound sizes compared with stable or positive trends. CONCLUSION: Albumin's utility as a bioindicator of short-term healing capability is limited to below-normal values.

Best practice for wound repair and regeneration use of cellular, acellular and matrix-like products (CAMPs).

There are currently over 80 biomaterials derived from autologous, allogeneic, synthetic and xenogeneic sources, or a combination of any or all these types of materials, available for soft-tissue coverage to effect wound closure. Often generically referred to as cellular and/or tissue-based products (CTPs), they are manufactured under various trade names and marketed for a variety of indications.

Triterpenes from Momordica balsamina (African pumpkin): ABCB1 inhibition and synergistic interaction with doxorubicin in resistant cancer cells.

Aiming at overcoming multidrug resistance (MDR) in cancer, we have been studying Momordica balsamina, a vegetable known as African pumpkin. Five undescribed cucurbitane-type triterpenoids (balsaminaepoxide, balsaminatriol, balsaminoic acid, balsaminal, and balsaminol G) along with five known cucurbitacins were isolated from the methanol extract of Momordica balsamina aerial parts, whose structures were elucidated by spectroscopic data, mainly 1D and 2D NMR experiments. Compounds were evaluated for their ability as P-glycoprotein (P-gp/ABCB1) inhibitors in multidrug resistant human ABCB1-transfected mouse lymphoma cells (L5178Y, MDR) and resistant human colon adenocarcinoma cells (COLO 320), using the rhodamine-123 exclusion test, by flow cytometry. Several compounds, which were found to be non-cytotoxic, strongly inhibited P-gp efflux activity in a dose-dependent manner in both cell models. In MRD mouse lymphoma cells, balsaminol G and karavilagenin B were the most active, while in resistant colon adenocarcinoma cells, the strongest inhibitory activity was found for balsaminaepoxide, balsaminatriol and karavilagenin C, being several-fold more active than the positive control verapamil. In chemosensitivity assays, in a model of combination chemotherapy, selected compounds showed to interact synergistically with doxorubicin, thus substantiating their potential as MDR reversers. The strongest synergistic interaction was found for balsaminal and balsaminol G.

Effectiveness of Home Gardening in Improving Food Security and Health in Chacraseca, Nicaragua: A Pilot Study.

We studied the usefulness of home gardening in improving food security and health. One hundred participants were randomized into the control and intervention group of which the intervention group received training in home gardening. Results showed that the percentage of participants with normal body mass index decreased from 24.4% to 20% in the control group whereas it remained unchanged in the intervention group. The number of participants in the very low food security category decreased from 66% (n=33) to 54% (n=27) in the intervention group whereas it increased from 68.8% (n=33) to 70.8% (n=34) in the control group. Results from the present study may be used to guide policymakers in designing or modifying home gardening interventions.

Skin substitutes with noncultured autologous skin cell suspension heal porcine full-thickness wounds in a one-stage procedure.

Clinical application of skin substitute is typically a two-stage procedure with application of skin substitute matrix to the wound followed by engraftment of a split-thickness skin graft (STSG). This two-stage procedure requires multiple interventions, increasing the time until the wound is epithelialised. In this study, the feasibility of a one-stage procedure by combining bioengineered collagen-chondroitin-6-sulfate (DS1) or decellularised fetal bovine skin substitute (DS2) with autologous skin cell suspension (ASCS) in a porcine full-thickness wound healing model was evaluated. Twelve full-thickness excisional wounds on the backs of pigs received one of six different treatments: empty; ASCS; DS1 with or without ASCS; DS2 with or without ASCS. The ASCS was prepared using a point-of-care device and was seeded onto the bottom side of DS1, DS2, and empty wounds at 80 000 cells/cm2 . Wound measurements and photographs were taken on days 0, 9, 14, 21, 28, 35, and 42 post-wounding. Histological analysis was performed on samples obtained on days 9, 14, 28, and 42. Wounds in the empty group or with ASCS alone showed increased wound contraction, fibrosis, and myofibroblast density compared with other treatment groups. The addition of ASCS to DS1 or DS2 resulted in a marked increase in re-epithelialisation of wounds at 14 days, from 15 ± 11% to 71 ± 20% (DS1 vs DS1 + ASCS) or 28 ± 14% to 77 ± 26 (DS2 vs DS2 + ASCS) despite different mechanisms of tissue regeneration employed by the DS used. These results suggest that this approach may be a viable one-stage treatment in clinical practice.

Analysis of community-level factors contributing to cholera infection and water testing access in the Northern Corridor of Haiti.

Vibrio cholera, the bacteria that cause cholera, is endemic in Haiti with a presence in both cities and remote areas. Improved access to drinking water testing and treatment in remote areas may reduce the impact of the disease. This case study uses correlation and regression analysis to identify the main factors that hinder access to water testing and that lead to high cholera infection rates among communities in the Northern Corridor of Haiti. Poor road conditions, mountainous terrain, and limited transportation options lead to high travel times up to 5.7 min/km between remote communities and drinking water testing facilities. The presence of springs in a community has a significant positive correlation with cholera infection rates in the Northern Corridor. However, socioeconomic factors had no significant correlation with cholera infection rate. The results of this study will be used to plan the implementation of a new drinking water testing laboratory near the city of Cap-Haitian and other programs for vulnerable remote areas. PRACTITIONER POINTS: Topography and road conditions may be more important than distance in determining the accessibility of water testing facilities for rural communities. A lack of access to private vehicles is a substantial challenge for many rural communities in accessing water testing. The presence of springs in a community had a significant positive correlation with cholera infection rate.

Benzoxazole-Based Metal Complexes to Reverse Multidrug Resistance in Bacteria.

Bacteria often show resistance against antibiotics due to various mechanisms such as the expression of efflux pumps, biofilm formation, or bacterial quorum sensing (QS) controls. For successful therapy, the discovery of alternative agents is crucial. The objective of this study was to evaluate the efflux pump, anti-biofilm, and QS inhibiting, as well as antibacterial effects of 2-trifluoroacetonylbenzoxazole ligands (1-3) and their metal complexes (4-12) in bacteria. The ligand 2 and its Zn(II) complex 5, and furthermore the Cu(II) complex 7 of ligand 1, exerted remarkable antibacterial activity on the Staphylococcus aureus 272123 (MRSA) strain. In the minimum inhibitory concentration (MIC) reduction assay the ligand 3, the Zn(II) complex 5 of ligand 2, and the Cu(II), Ni(II), Mg(II), Fe(III) complexes (7, 8, 9, 12) of ligand 1 enhanced the antibacterial activity of ciprofloxacin in MRSA. An increased ethidium bromide accumulation was detected for ligand 3 in MRSA while the Fe(III) complex 12 of ligand 1 decreased the biofilm formation of the reference S. aureus ATCC 25923 strain. The Zn(II) and Ag(II) complexes (3 and 4) of ligand 1 and ligand 3 inhibited the QS. Based on our results, the ligands and their metal complexes could be potential alternative drugs in the treatment of infectious diseases.

A Method to Reproduce Symmetry in Midfacial Reconstruction: A Report of 19 Cases.

BACKGROUND: Reconstruction of facial skin defects remains a clinical challenge. With aging, ptosis of tissue over fixed structures creates an important facial feature known as the tear trough. This study aimed to evaluate the efficacy and aesthetic outcome of a novel surgical technique that reproduced this facial feature while avoiding ectropion during midfacial skin defect repair. METHODS: Nineteen patients with midfacial skin defects received local flap reconstruction combined with an anchoring suture. The flap was designed in a unilateral pedicled V-Y pattern. When the flap was advanced to cover the defect, one or two sutures that connected the dermis of the flap with the infraorbital periosteum were made to reproduce the tear trough line. RESULTS: Midfacial defects were successfully repaired with the V-Y flap in all 19 patients. No lower eyelid ectropion or conspicuous scars were noted in any of the patients. Further, the tear trough was successfully reconstructed in each patient. Facial symmetry was maintained with static positioning and animation. CONCLUSIONS: The combination of local V-Y flap reconstruction with anchoring sutures to reproduce facial feature lines is an effective technique in midfacial skin defect repair.

Organosilicon Compounds, SILA-409 and SILA-421, as Doxorubicin Resistance-Reversing Agents in Human Colon Cancer Cells.

Multidrug resistance (MDR) that occurs in cancer cells constitutes one of the major reasons for chemotherapy failure. The main molecular mechanism of MDR is overexpression of protein transporters from the ATP-binding cassette (ABC) superfamily, such as ABCB1 (multidrug resistance protein 1 (MDR1), P-glycoprotein). At the expense of ATP hydrolysis, ABCB1 pumps a diverse range of substrates (including anticancer drugs) out of the cell, thereby reducing their intracellular concentration. In the present study, the ability of two patented disiloxanes (SILA-409 and SILA-421) to reverse drug resistance in human colon adenocarcinoma cell lines LoVo and LoVo/Dx was investigated. It was demonstrated that both compounds in concentrations of 0.5-1 µM strongly increased the sensitivity of LoVo/Dx cells to doxorubicin. By means of an accumulation test in which rhodamine 123 was used as an ABCB1 substrate analogue, both organosilicon compounds were also shown to inhibit ABCB1 transport activity. The intracellular accumulation of doxorubicin was also increased, and more drug entered the cellular nuclei of resistant cells in the presence of the studied compounds. In conclusion, both SILA-409 and SILA-421 were demonstrated to be effective MDR reversal agents in resistant human colon cancer cells.

Initial Experience With Autologous Skin Cell Suspension for Treatment of Deep Partial-Thickness Facial Burns.

Facial burns present a challenge in burn care, as hypertrophic scarring and dyspigmentation can interfere with patients' personal identities, ocular and oral functional outcomes, and have long-term deleterious effects. The purpose of this study is to evaluate our initial experience with non-cultured, autologous skin cell suspension (ASCS) for the treatment of deep partial-thickness (DPT) facial burns. Patients were enrolled at a single burn center during a multicenter, prospective, single-arm, observational study involving the compassionate use of ASCS for the treatment of large total BSA (TBSA) burns. Treatment decisions concerning facial burns were made by the senior author. Facial burns were initially excised and treated with allograft. The timing of ASCS application was influenced by an individual's clinical status; however, all patients were treated within 30 days of injury. Outcomes included subjective cosmetic parameters and the number of reoperations within 3 months. Five patients (4 males, 1 female) were treated with ASCS for DPT facial burns. Age ranged from 2.1 to 40.7 years (mean 18.2 ± 17.3 years). Average follow-up was 231.2 ± 173.1 days (range 63-424 days). Two patients required reoperation for partial graft loss within 3 months in areas of full-thickness injury. There were no major complications and one superficial hematoma. Healing and cosmetic outcomes were equivalent to, and sometimes substantially better than, outcomes typical of split-thickness autografting. Non-cultured, ASCS was successfully used to treat DPT facial burns containing confluent dermis with remarkable cosmetic outcomes. Treatment of DPT burns with ASCS may be an alternative to current treatments, particularly in patients prone to dyspigmentation, scarring sequelae, and with limited donor sites.

Bioprinted Skin Recapitulates Normal Collagen Remodeling in Full-Thickness Wounds.

Over 1 million burn injuries are treated annually in the United States, and current tissue engineered skin fails to meet the need for full-thickness replacement. Bioprinting technology has allowed fabrication of full-thickness skin and has demonstrated the ability to close full-thickness wounds. However, analysis of collagen remodeling in wounds treated with bioprinted skin has not been reported. The purpose of this study is to demonstrate the utility of bioprinted skin for epidermal barrier formation and normal collagen remodeling in full-thickness wounds. Human keratinocytes, melanocytes, fibroblasts, dermal microvascular endothelial cells, follicle dermal papilla cells, and adipocytes were suspended in fibrinogen bioink and bioprinted to form a tri-layer skin structure. Bioprinted skin was implanted onto 2.5 × 2.5 cm full-thickness excisional wounds on athymic mice, compared with wounds treated with hydrogel only or untreated wounds. Total wound closure, epithelialization, and contraction were quantified, and skin samples were harvested at 21 days for histology. Picrosirius red staining was used to quantify collagen fiber orientation, length, and width. Immunohistochemical (IHC) staining was performed to confirm epidermal barrier formation, dermal maturation, vascularity, and human cell integration. All bioprinted skin treated wounds closed by day 21, compared with open control wounds. Wound closure in bioprinted skin treated wounds was primarily due to epithelialization. In contrast, control hydrogel and untreated groups had sparse wound coverage and incomplete closure driven primarily by contraction. Picrosirius red staining confirmed a normal basket weave collagen organization in bioprinted skin-treated wounds compared with parallel collagen fibers in hydrogel only and untreated wounds. IHC staining at day 21 demonstrated the presence of human cells in the regenerated dermis, the formation of a stratified epidermis, dermal maturation, and blood vessel formation in bioprinted skin, none of which was present in control hydrogel treated wounds. Bioprinted skin accelerated full-thickness wound closure by promoting epidermal barrier formation, without increasing contraction. This healing process is associated with human cells from the bioprinted skin laying down a healthy, basket-weave collagen network. The remodeled skin is phenotypically similar to human skin and composed of a composite of graft and infiltrating host cells. Impact statement We have demonstrated the ability of bioprinted skin to enhance closure of full-thickness wounds through epithelialization and normal collagen remodeling. To our knowledge, this article is the first to quantify collagen remodeling by bioprinted skin in full-thickness wounds. Our methods and results can be used to guide further investigation of collagen remodeling by tissue engineered skin products to improve ongoing and future bioprinting skin studies. Ultimately, our skin bioprinting technology could translate into a new treatment for full-thickness wounds in human patients with the ability to recapitulate normal collagen remodeling in full-thickness wounds.

Vitamin A and Wound Healing.

Vitamin A is a general term for retinoids. Vitamin A deficiency leads to a variety of cutaneous manifestations. It also functions as a hormone through retinoic acid receptors altering the activity of multiple cell lines. Pancreatic vitamin A levels are critical for retinoid signaling and normal pancreatic control of glucose. Vitamin A deficiency is more common during infection, and supplementation reduces severe morbidity and mortality from infectious diseases. Vitamin A modulates activities at the cellular level and, via its interrelationship with hormones such as thyroid, insulin, and corticosteroids, has diffuse metabolic effects on the body. It plays an important role in all stages of wound healing. Vitamin A is known for its ability to stimulate epithelial growth, fibroblasts, granulation tissue, angiogenesis, collagen synthesis, epithelialization, and fibroplasia. Local (topical) and systemic supplementation with vitamin A has been proven to increase dermal collagen deposition. There are numerous animal studies and limited human studies regarding physiologic effect of vitamin A on acute or chronic wounds via systemic or topical administration. The most common use of vitamin A supplementation is to offset steroids' effect. When considering supplementation, the potential benefits must be weighed against the risk of harm. Vitamin A toxicity can be critical and even result in death. The evidence for supplementation with vitamin A is currently limited to expert opinion and is not backed up by rigorous trials. There is an acute need for therapeutic trials with vitamin A supplementations.

Dually Acting Nonclassical 1,4-Dihydropyridines Promote the Anti-Tuberculosis (Tb) Activities of Clofazimine.

The number of effective antituberculotic drugs is strongly limited to four first-line drugs in standard therapy. In case of resistances second-line antibiotics are used with a poor efficacy and tolerability. Therefore, novel antituberculotic drugs are urgently needed. We synthesized novel nonclassical 1,4-dihydropyridines and evaluated their antituberculotic properties depending on substituent effects. Preferred substituents could be identified. As related classical 1,4-dihydropyridines are known as inhibitors of the transmembrane efflux pump ABCB1 in cancer cells, we wondered whether a use of our compounds may be of favour to enhance the antituberculotic drug efficacy of the second-line antituberculotic drug clofazimine, which is a known substrate of ABCB1 by a suggested inhibition of a corresponding efflux pump in Mycobacterium tuberculosis (Mtb). For this, we determined the ABCB1 inhibiting properties of our compounds in a mouse T-lymphoma cell line model and then evaluated the drug-enhancing properties of selected compounds in a co-application with clofazimine in our Mtb strain. We identified novel enhancers of clofazimine toxicity which could prevent clofazimine resistance development mediated by an efflux pump activity.

Effective MDR reversers through phytochemical study of Euphorbia boetica.

INTRODUCTION: Macrocyclic diterpenes from Euphorbia species were found to be promising modulators of multidrug resistance (MDR), a complex phenomenon that hampers the effectiveness of cancer therapy. OBJECTIVE: To find new effective MDR reversers through the phytochemical study of E. boetica, including isolation and molecular derivatisation. MATERIAL AND METHODS: The phytochemical study of E. boetica was performed through chromatographic techniques. Preliminary analysis of crude chromatographic fractions from the methanol extract was carried out by 1 H-NMR in order to prioritise the study of those having macrocyclic diterpenes. Polyamide resin was used to remove chlorophylls. Molecular derivatisation of isolated compounds comprised hydrolysis, reduction and acylation reactions. The structural identification of compounds was performed through analysis of spectroscopic data, mainly one-dimensional- and two-dimensional-NMR. The MDR reversing activity was assessed using a combination of transport and chemosensitivity assays, in mouse lymphoma (L5178Y-MDR) and Colo320 cell models. RESULTS: The 1 H-NMR study of crude fractions and application of a straightforward method to remove chlorophylls, allowed the effortless isolation of two lathyrane-type diterpenes in large amounts, including the new polyester, euphoboetirane B (1). Taking advantage of the chemical functions of 1, 13 new derivatives were prepared. Several compounds showed to be promising modulators of P-glycoprotein (P-gp), in resistant cancer cells. Most of the compounds tested revealed to interact synergistically with doxorubicin. CONCLUSION: These results corroborate the importance of macrocyclic lathyrane diterpenes as effective lead compounds for the reversal of MDR.

Current and Future Perspectives on Skin Tissue Engineering: Key Features of Biomedical Research, Translational Assessment, and Clinical Application.

The skin is responsible for several important physiological functions and has enormous clinical significance in wound healing. Tissue engineered substitutes may be used in patients suffering from skin injuries to support regeneration of the epidermis, dermis, or both. Skin substitutes are also gaining traction in the cosmetics and pharmaceutical industries as alternatives to animal models for product testing. Recent biomedical advances, ranging from cellular-level therapies such as mesenchymal stem cell or growth factor delivery, to large-scale biofabrication techniques including 3D printing, have enabled the implementation of unique strategies and novel biomaterials to recapitulate the biological, architectural, and functional complexity of native skin. This progress report highlights some of the latest approaches to skin regeneration and biofabrication using tissue engineering techniques. Current challenges in fabricating multilayered skin are addressed, and perspectives on efforts and strategies to meet those limitations are provided. Commercially available skin substitute technologies are also examined, and strategies to recapitulate native physiology, the role of regulatory agencies in supporting translation, as well as current clinical needs, are reviewed. By considering each of these perspectives while moving from bench to bedside, tissue engineering may be leveraged to create improved skin substitutes for both in vitro testing and clinical applications.