Evaluation of viscoelastic parameters and photo-based assessment of newly developed dermal substitutes modified with thermostabilized fibroblast growth factor 2.

BACKGROUND: The purpose of dermal substitutes is to mimic the basic properties of the extracellular matrix of human skin. The application of dermal substitutes to the defect reduces the formation of hypertrophic scars and improves the scar quality. This study aims to develop an original dermal substitute enriched with stable fibroblast growth factor 2 (FGF2-STAB®) and test it in an animal model. METHODS: Dermal substitutes based on collagen/chitosan scaffolds or collagen/chitosan scaffolds with nanofibrous layer were prepared and enriched with FGF2-STAB® at concentrations of 0, 0.1, 1.0, and 10.0 µg ‧ cm-2. The performance of these dermal substitutes was tested in vivo on artificially formed skin defects in female swine. The outcomes were evaluated using cutometry at 3 and 6 months. In addition, visual appearance was assessed based on photos of the scars at 1-month, 3-month and 6-month follow-ups using Yeong scale and Visual Analog Scale. RESULTS: The dermal substitute was fully integrated into all defects and all wounds healed successfully. FGF2-STAB®-enriched matrices yielded better results in cutometry compared to scaffolds without FGF2. Visual evaluation at 1, 3, and 6 months follow-ups detected no significant differences among groups. The FGF2-STAB® effectiveness in improving the elasticity of scar tissues was confirmed in the swine model. This effect was independently observed in the scaffolds with nanofibres as well as in the scaffolds without nanofibres. CONCLUSION: The formation of scars with the best elasticity was exhibited by addition 1.0 µg ‧ cm-2of FGF2-STAB® into the scaffolds, although it had no significant effect on visual appearance at longer follow-ups. This study creates the basis for further translational studies of the developed product and its progression into the clinical phase of the research.

Updates on Recent Clinical Assessment of Commercial Chronic Wound Care Products.

Impaired wound healing after trauma, disorders, and surgeries impact millions of people globally every year. Dysregulation in orchestrated healing mechanisms and underlying medical complications make chronic wound management extremely challenging. Besides standard-of-care treatments including broad spectrum antibiotics and wound-debridement, novel adjuvant therapies are clinically tested and commercialized. These include topical agents, skin substitutes, growth factor delivery, and stem cell therapies. With a goal to overcome factors playing pivotal role in delayed wound healing, researchers are exploring novel approaches to elicit desirable healing outcomes in chronic wounds. Although recent innovations in wound care products, therapies, and devices are extensively reviewed in past, a comprehensive review summarizing their clinical outcomes is surprisingly lacking. Herein, this work reviews the commercially available wound care products and their performance in clinical trials to provide a statistically comprehensive understanding of their safety and efficacy. The performance and suitability of various commercial wound care platforms, including xenogeneic and allogenic products, wound care devices, and novel biomaterials, are discussed for chronic wounds. The current clinical evaluation will provide a comprehensive understanding of the benefits and drawbacks of the most-recent approaches and will enable researchers and healthcare providers to develop next-generation technologies for chronic wound management.

The Economic Impact of Living Cell Tissue Products in Treating Diabetic Foot Ulcers and Venous Leg Ulcers in Patients with Commercial Insurance: A Retrospective Matched-Cohort Study.

OBJECTIVE: Previous studies demonstrated that costs paid on behalf of Medicare recipients for diabetic foot ulcers and venous leg ulcers treated with cellular and/or tissue-based products (CTPs) varied in part based on the CTP chosen. This study extends previous work to determine how costs vary when paid by commercial insurance carriers. METHODS: A retrospective matched-cohort intent-to-treat design was used to analyze commercial insurance claims data between January 2010 and June 2018. Study participants were matched using Charlson Comorbidity Index, age, sex, type of wound, and geographic location within the US. Patients treated with a bilayered living cell construct (BLCC), dermal skin substitute (DSS), or cryopreserved human skin (CHSA) were included. RESULTS: Wound-related costs and number of CTP applications were significantly lower for CHSA relative to BLCC and DSS at all time intervals (60, 90, and 180 days and 1 year after first application of the CTP). Further, CHSA was associated with significantly fewer amputations at 1 year relative to DSS (14.9% vs 19.7%, P = .03). CONCLUSIONS: There was a statistically significant reduction in cost of treating diabetic foot ulcers (BLCC, DSS, CHSA) and venous leg ulcers (BLCC, CHSA) with CHSA as compared with the other CTPs. These findings are attributed to fewer applications, lower wound care costs, and comparable or reduced incidence of amputation. These commercial insurance data are consistent with prior studies that examined Medicare expenditures.

Safety Assessment of Starch Nanoparticles as an Emulsifier in Human Skin Cells, 3D Cultured Artificial Skin, and Human Skin.

Emulsion systems are widely used in various industries, including the cosmetic, pharmaceutical, and food industries, because they require emulsifiers to stabilize the inherently unstable contact between oil and water. Although emulsifiers are included in many products, excessive use of emulsifiers destroys skin barriers and causes contact dermatitis. Accordingly, the consumer demand for cosmetic products made from natural ingredients with biocompatibility and biodegradability has increased. Starch in the form of solid nanosized particles is considered an attractive emulsifier that forms and stabilizes Pickering emulsion. Chemical modification of nanosized starch via acid hydrolysis can effectively provide higher emulsion stability. However, typical acid hydrolysis limits the industrial application of starch due to its high time consumption and low recovery. In previous studies, the effects of starch nanoparticles (SNPs) prepared by treatment with acidic dry heat, which overcomes these limitations, on the formation and stability of Pickering emulsions were reported. In this study, we evaluated the safety of SNPs in skin cell lines, 3D cultured skin, and human skin. We found that the cytotoxicity of SNPs in both HaCaT cells and HDF cells could be controlled by neutralization. We also observed that SNPs did not induce structural abnormalities on 3D cultured skin and did not permeate across micropig skin tissue or human skin membranes. Furthermore, patches loaded with SNPs were found to belong in the "No irritation" category because they did not cause any irritation when placed on human skin. Overall, the study results suggest that SNPs can be used as a safe emulsifier in various industries, including in cosmetics.

In Vitro Assessment of Sunscreen Efficacy Using Fourier Transform Infrared (FTIR) Spectroscopy on Synthetic Skin.

Although there are several methods for assessing the sun protection factor (SPF) of sunscreen products, there is no standard and reliable in vitro method. Each test entails limitations and drawbacks. Therefore, this study aimed to assess the employability of FTIR as an alternative and quick method to evaluate the efficacy of various sunscreen formulations, their concentrations, and the timing of their application. Infrared radiation has longer wavelengths than ultraviolet, penetrates deeply into the skin, and hence enables the understanding of sunscreens' ability to block the transmission of radiation. The FTIR transmission using synthetic skin to study the effect of sunscreen agents (oxybenzone, octyl methoxycinnamate, titanium dioxide (TiO2), and zinc oxide (ZnO)) was conducted in the range 450-4000cm-1. Comparison studies were made at the peak of 805cm-1. After 2 h of sunscreen application, using the maximum concentrations, the FTIR peak at wavenumber 805cm-1 demonstrated a significant reduction of transmission from 96.55 to 60.09%, 57.59%, 32.02%, and 37.1% for oxybenzone, octyl methoxycinnamate, TiO2, and ZnO respectively (P<0.05). A significant reduction in transmission was observed (P<0.05) with increasing sunscreen concentrations after 2 h of application. Nevertheless, the upper limit of concentration showed no appreciable change from the middle level of concentration, and hence it is cost-effective to employ the middle concentration. Inorganic sunscreens showed a higher protection level than organic. Fixed-dose combinations of sunscreens showed an enhanced effect yet were not synergistic. In conclusion, the use of FTIR spectroscopy with synthetic skin is a quick and user-friendly technique that enables the assessment of the efficacy of sunscreen formulations.

Skin Substitutes for Adults With Diabetic Foot Ulcers and Venous Leg Ulcers: A Health Technology Assessment.

BACKGROUND: Wounds may be caused in a variety of ways. Some wounds are difficult to heal, such as diabetic foot ulcers and venous leg ulcers. We conducted a health technology assessment of skin substitutes for adults with neuropathic diabetic foot ulcers and venous leg ulcers, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding skin substitutes, and patient preferences and values. METHODS: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane risk-of-bias tool for randomized studies (version 2), and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-utility analysis with a 26-week time horizon from a public payer perspective. We also analyzed the budget impact of publicly funding skin substitutes in adults with diabetic foot ulcers and venous leg ulcers in Ontario. We explored the underlying values, needs, and priorities of those who have lived experience with diabetic leg ulcers and venous leg ulcers, as well as their preferences for and perceptions of skin substitutes. RESULTS: We included 40 studies in the clinical evidence review. Adults with difficult-to-heal neuropathic diabetic foot ulcers who used dermal (GRADE: High) or multi-layered (GRADE: Moderate) skin substitutes as an adjunct to standard care were more likely to experience complete wound healing than those whose who used standard care alone. Adults with difficult-to-heal venous leg ulcers who used dermal (GRADE: Moderate) or multi-layered (GRADE: High) skin substitutes as an adjunct to standard care were more likely to experience complete wound healing than those who used standard care alone. The evidence for the effectiveness of epidermal skin substitutes was inconclusive for venous leg ulcers because of the small size of the individual studies (GRADE: Very low). We found no studies on epidermal skin substitutes for diabetic foot ulcers. We could not evaluate the safety of skin substitutes versus standard care, because the number of adverse events was either very low or zero (because sample sizes were too small).In our economic analysis, the use of skin substitutes as an adjunct to standard care was more costly and more effective than standard care alone for the treatment of difficult-to-heal diabetic foot ulcers and venous leg ulcers. For diabetic foot ulcers, the incremental cost-effectiveness ratio (ICER) of skin substitutes plus standard care compared with standard care alone was $48,242 per quality-adjusted life-year (QALY), and the cost per ulcer-free week was $158. For venous leg ulcers, the ICER was $1,868,850 per QALY, and the cost per ulcer-free week was $3,235. At the commonly used willingness-to-pay of $50,000 per QALY, the cost-effectiveness of skin substitutes plus standard care versus standard care alone was uncertain (47% probability of being cost-effective) for diabetic foot ulcers and highly unlikely (0% probability of being cost-effective) for venous leg ulcers. At the commonly used willingness-to-pay of $100,000 per QALY, the cost-effectiveness of skin substitutes plus standard care versus standard care alone was moderately likely (71% probability of cost-effectiveness) for people with diabetic foot ulcers and highly unlikely (0% probability of being cost-effective) for people with venous leg ulcers. The annual budget impact of publicly funding skin substitutes in Ontario over the next 5 years would range from an additional $0.17 million in year 1 to $1.2 million in year 5 for people with diabetic foot ulcers, and from $1 million in year 1 to $7.7 million in year 5 for people with venous leg ulcers.Direct patient engagement consisted of three participants for this assessment and 51 from previous health technology assessments that addressed interventions for diabetic foot ulcers and venous leg ulcers. Participants spoke of the negative impact on their quality of life with regard to mobility, employment, social activities, and emotional and mental health. No participants had direct experience using skin substitutes, but participants were open to this treatment option. Barriers to access included the limited use of skin substitutes across Ontario, lack of knowledge of skin substitutes among people with diabetic foot ulcers and venous leg ulcers, and cost. CONCLUSIONS: Dermal and multi-layered skin substitutes, when used as an adjunct to standard care, were more effective than standard care alone in completely healing difficult-to-heal neuropathic diabetic foot ulcers and venous leg ulcers in adults. Using skin substitutes as an adjunct to standard care was more costly and more effective than standard care alone for the treatment of difficult-to-heal neuropathic diabetic foot ulcers and venous leg ulcers. For adults with diabetic foot ulcers, the likelihood of skin substitutes being cost-effective compared with standard care depends on the willingness to pay. The likelihood of skin substitutes being cost-effective compared with standard care is uncertain at $50,000 per QALY and moderately likely at $100,000 per QALY. For adults with venous leg ulcers, skin substitutes were highly unlikely to be cost-effective compared with standard care. We estimated that publicly funding skin substitutes in Ontario would result in additional costs of $3 million and $20 million over the next 5 years for people with diabetic foot ulcers and venous leg ulcers, respectively. The people with diabetic foot ulcers and venous leg ulcers we spoke with were open to using skin substitutes as a treatment option.

Observed impact of skin substitutes in lower extremity diabetic ulcers: lessons from the Medicare Database (2015-2018).

OBJECTIVE: To evaluate large propensity-matched cohorts to assess outcomes in patients receiving advanced treatment (AT) with skin substitutes for lower extremity diabetic ulcers (LEDUs) versus no AT (NAT) for the management of LEDUs. METHOD: The Medicare Limited Dataset (1 October 2015 through 2 October 2018) were used to retrospectively analyse people receiving care for a LEDU treated with AT or NAT (propensity-matched Group 1). Analysis included major and minor amputations, emergency department (ED) visits and hospital readmissions. In addition, AT following parameters for use (FPFU) was compared with AT not FPFU (propensity-matched Group 2). A paired t-test was used for comparisons of the two groups. For comparisons of three groups, the Kruskal-Wallis test was used. A Bonferroni correction was performed when multiple comparisons were calculated. RESULTS: There were 9,738,760 patients with a diagnosis of diabetes, of whom 909,813 had a LEDU. In propensity-matched Group 1 (12,676 episodes per cohort), AT patients had statistically fewer minor amputations (p=0.0367), major amputations (p<0.0001), ED visits (p<0.0001), and readmissions (p<0.0001) compared with NAT patients. In propensity-matched Group 2 (1131 episodes per cohort), AT FPFU patients had fewer minor amputations (p=0.002) than those in the AT not FPFU group. CONCLUSION: AT for the management of LEDUs was associated with significant reductions in major and minor amputation, ED use, and hospital readmission compared with LEDUs managed with NAT. Clinics should implement AT in accordance with the highlighted parameters for use to improve outcomes and reduce costs.

Treatment of venous leg ulcers using bilayered living cellular construct.

Background: Venous leg ulcers (VLUs) present a significant economic burden on the US healthcare system and payers (US$14.9 billion). Aim: To evaluate the quality of life (QoL) of patients with VLUs; to analyze the limitations of standard of care (SOC) for VLUs; and to explain how using bilayered living cellular construct (BLCC) with SOC for treatment of VLUs can help heal more VLUs faster (than using SOC alone) as well as help improve QoL and help reduce the burden on the US healthcare system and payers. Materials & methods: This is a review study. The search was conducted in February 2020 by way of electronic databases to find relevant articles that provided information related to QoL of patients with VLUs, limitations of SOC for VLUs and economic analyses of using BLCC for treatment of VLUs. Results: VLUs impact patients' physical, functional and psychological status and reduce QoL. A total 75% of VLU patients who used SOC alone failed to achieve healing in a timely fashion, which led to increased healthcare costs and healthcare resource utilization. Although the upfront cost is high, the greater effectiveness of BLCC offsets the added cost of the product during the time period of the studies. Therefore, BLCC helps to improve the QoL of VLU patients. As an example, for every 100 VLU patients in a healthcare plan, the use of BLCC can create cost savings of US$1,349,829.51. Conclusion: Payers' coverage of BLCC results in reduction of the overall medical cost for treating VLU patients.

Assessment of Materials to Prevent Sutures Cutting Through Atrophic Skin.

BACKGROUND: Sutures can tear through thin skin, especially in the elderly. To reinforce thin skin, several materials have been suggested through which sutures may be placed. OBJECTIVE: To evaluate the relative tear-through resistance to suture provided by various materials applied to a skin substitute. MATERIALS/METHODS: We measured the force needed for 3-0 polypropylene suture to tear through an artificial skin substitute, both alone and after various materials were applied. These materials included wound closure tapes, nonwoven polyester tape, hydrocolloid dressing, polyethylene film, and cyanoacrylate glue. The Student t-test and one-way analysis of variance were used to determine differences in the mean forces. RESULTS: Reinforced wound closure tape and nonwoven polyester tape were superior to the other materials, and provided a 3.1-fold and 3.6-fold increase in tear-through resistance, respectively, compared with skin substitute alone (p < .001). Orientation of wound closure tape and nonwoven polyester tape with their reinforcing fibers placed parallel to the skin substitute edge provided increased tear-through resistance compared with perpendicular placement. Affixing these latter materials with liquid adhesive also improved holding strength. CONCLUSION: Reinforced wound closure tape and nonwoven polyester tape, when applied to a skin substitute, provide significantly increased tear-through resistance to suture compared with skin substitute alone.

Comparative Effectiveness Analysis of Complex Lower Extremity Reconstruction: Outcomes and Costs for Biologically Based, Local Tissue Rearrangement, and Free Flap Reconstruction.

BACKGROUND: Various surgical techniques exist for lower extremity reconstruction, but limited high-quality data exist to inform treatment strategies. Using multi-institutional data and rigorous matching, the authors evaluated the effectiveness and cost of three common surgical reconstructive modalities. METHODS: All adult subjects with lower extremity wounds who received bilayer wound matrix, local tissue rearrangement, or free flap reconstruction were retrospectively reviewed (from 2010 to 2017). Cohorts' comorbidities and wound characteristics were balanced. Graft success at 180 days was the primary outcome; readmissions, reoperations, and costs were secondary outcomes. RESULTS: Five hundred one subjects (166 matrix, 190 rearrangement, and 145 free flap patients) were evaluated. Matched subjects (n = 312; 104/group) were analyzed. Reconstruction success at 180 days for matrix, local tissue rearrangement, and free flaps was 69.2 percent, 91.3 percent, and 93.3 percent (p < 0.001), and total costs per subject were $34,877, $35,220, and $53,492 (p < 0.001), respectively. Median length of stay was at least 2 days longer for free flaps (p < 0.0001). Readmissions and reoperations were greater for free flaps. Local tissue rearrangement, if achievable, provided success at low cost. Free flaps were effective with large, traumatic wounds but at higher costs and longer length of stay. Matrices successfully treated older, obese patients without exposed bone. CONCLUSIONS: Lower extremity reconstruction can be performed effectively using multiple modalities with varying degrees of success and costs. Local tissue rearrangement and free flaps demonstrate success rates greater than 90 percent. Bilayer wound matrix-based reconstruction effectively treats a distinct patient population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The Health Economic Impact of Living Cell Tissue Products in the Treatment of Chronic Wounds: A Retrospective Analysis of Medicare Claims Data.

OBJECTIVE: To investigate differences in wound-related costs; product waste; lower-extremity amputations; and number of applications, hospitalizations, and emergency room visits among patients treated with three cellular and/or tissue-based products. METHODS: This retrospective intent-to-treat matched-cohort study analyzed the full Medicare claims dataset from 2011 to 2014. Patients who received either a bilayer cellular construct (BLCC), dermal skin substitute (DSS), or cryopreserved human skin allograft (CHSA) were concurrently matched for Charlson Comorbidity Index, age, sex, and region, resulting in 14,546 study patients. Key variables were reported at 60, 90, and 180 days after the first product application. RESULTS: There were no statistically significant differences in the distribution of Charlson Comorbidity Index, age, sex, and region among cohorts. Wound-related costs and product wastage were lower for CHSA patients relative to both BLCC and DSS patients at all time intervals (P < .05). Patients treated with CHSA received fewer product applications than DSS at 90 and 180 days (P < .05). Amputations were significantly higher among patients treated with DSS than either CHSA or BLCC (P < .0001). CONCLUSIONS: The data demonstrate that wound-related costs, product waste, amputations, and frequency of applications are lower for CHSA than DSS. Wound-related costs and product waste are lower for CHSA compared with BLCC. Further claims analysis and prospective clinical trials could help develop appropriate quality measures and reimbursement models to ensure smarter spending for the growing population of patients with chronic wounds.

Spray on skin for diabetic foot ulcers: an open label randomised controlled trial.

BACKGROUND: One Australian loses a limb every 3 h as a result of infected diabetic foot ulcers (DFU). This common condition accounts for substantial morbidity and mortality for affected individuals and heavy economic costs for the health sector and the community. There is an urgent need to test interventions that improve wound healing time, prevent amputations and recurrent ulceration in patients presenting with DFU whilst improving quality of life and reducing health care costs. METHODS: One hundred and fifty eligible participants will be randomised to receive an autologous skin cell suspension, also termed 'spray-on' skin (ReCell®) or standard care interventions for their DFU. The primary outcome is complete wound healing at 6 months, but participants will be followed up for a total of 12 months to enable secondary outcomes including total overall costs, ulcer free days at 12 months and quality of life to be assessed. DISCUSSION: Outpatient costs for dressings, home nursing visits and outpatient appointments are key cost drivers for DFU. If spray-on skin is effective, large cost savings to WA Health will be realised immediately through a shortened time to healing, and through a higher proportion of patients achieving complete healing. Shortened healing times may enable participants to return to work earlier. Any economic benefits are likely to be amplified across Australia and other similar demographic settings where aging populations with increased diabetes rates are considered major future challenges. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000511235. Registered on 9 April 2018.

Transplant of Tissue-Engineered Artificial Autologous Human Skin in Andalusia: An Example of Coordination and Institutional Collaboration.

A new model of tissue-engineered artificial autologous human skin developed in Andalusia is currently being transplanted into patients suffering from large burns within the Andalusian Public Healthcare System. This product is considered an advanced therapy medicinal product (ATMP) in Europe, and its clinical use implies meeting transplant and medicinal product legal requirements, being the Guidelines of Good Manufacturing Practice for ATMPs of particular importance. The preclinical research and clinical translation of the product have represented a technical, regulatory, and organizational challenge, which has taken 10 years since the first preclinical experiments were designed. Twelve patients with large burns, including 3 pediatric patients, have hitherto received artificial autologous skin grafts with an overall survival rate of 75% and positive clinical, homeostatic, and histologic results. Achieving such a milestone within our Healthcare System was possible through a multidisciplinary approach and the joint efforts of multiple publicly funded institutions and units under the coordination of the Andalusian Initiative for Advanced Therapies. In this article, we present the organizational model set up to facilitate collaboration and logistics among the professionals involved, totaling more than 80 people. The similarities between the tissue-engineered artificial autologous human skin transplant and other organ and tissue transplants, in terms of logistic requirements, reveal how regional and hospital transplant coordination have played a crucial role.

Health economics for treatment of diabetic foot ulcers: a cost-effectiveness analysis of eight skin substitutes.

AIM: Skin substitutes are frequently used to treat chronic diabetic foot ulcers (DFU), and many different options are available. While the clinical efficacy of many products has been evaluated, a comprehensive cost-effectiveness analysis comparing the most popular skin substitutes and using the most recent cost data has been lacking. METHODS: This study compared eight skin substitutes using published efficacy rates combined with the Centers for Medicare and Medicaid Services (CMS) 2018 cost data. The study criteria resulted in the inclusion of seven studies that described efficacy rates for treatment of DFUs using the skin substitutes. RESULTS: The results revealed wide discrepancies between these skin substitutes for the costs of treatments and healing rates in hospital outpatient departments and physician office settings. Healing rates for 12 and 16 weeks ranged from 28% to 68%, while the average cost for treating one DFU varied from $2001 to $14,507 and $1207 to $8791 in the hospital outpatient department and physician's office setting, respectively. The estimated patient share of costs for treating a single DFU ranged from $400 to $2901 and $241 to $1758 in the hospital outpatient department and physician's office setting, respectively. Most importantly, the estimated number of wounds healed out of 100 DFUs per $1000 expenditure with each patient ranged from 3.9-26.5 DFUs in the hospital outpatient department, and 4.3-36.4 DFUs in the physicians' office setting. CONCLUSIONS: This study revealed that the costs of a skin substitute itself did not necessarily correlate with its healing efficacy. These results provide a comprehensive cost-effectiveness analysis to enable integrated health-care systems, health professionals and reimbursement payers to make informed value decisions when treating DFUs.

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.

ReCell® Spray-On Skin System for Treating Skin Loss, Scarring and Depigmentation after Burn Injury: A NICE Medical Technology Guidance.

The gold standard treatment for deep burns is an autologous skin graft; in larger burns this may be meshed to increase the area covered. However, long-term aesthetic and functional outcomes of graft scars may be poor. ReCell® is a medical device that processes skin samples in the operating theatre into a cell suspension to be sprayed or dripped onto a wound. It is claimed to improve healing and scar appearance. This device was evaluated by the National Institute for Health and Care Excellence (NICE) Medical Technologies Evaluation Programme. Two groups were defined: ReCell compared to conventional dressings in shallower burns, and meshed grafts plus ReCell compared to meshed grafts alone in larger deeper burns. The manufacturer's clinical evidence submission included three papers and eight conference abstracts. The External Assessment Centre (EAC) excluded two of these and added seven abstracts. In general, the evidence did not fit the defined groups, but suggested that ReCell was clinically comparable to skin grafts for partial thickness burns; however, ReCell is not used in this way in the UK. The manufacturer submitted an economic model in which ReCell treatment of partial thickness burns reduced the requirement for later skin grafts. This indicated that ReCell alone was cost saving in comparison to conventional dressings. The EAC indicated that this model was clinically inappropriate, but data were not available to populate a new model. NICE Medical Technologies Guidance 21 recommended that additional research was needed to address the uncertainties regarding the potential benefits of ReCell.

[Study on rapid recognition technique of schistosome susceptibility water body I Animal skin making and effect assessment].

OBJECTIVE: To develop a bionic animal skin and evaluate its detective effect of Schistosoma japonicum cercariae so as to provide a new technique for the monitoring of the schistosome susceptibility water body. METHODS: A bionic animal skin was made with pigskin and the experiments were carried out for evaluating its detective effects of S. japonicum cercariae in laboratory and simulate fields, and at the same time, the sentinel mouse method was used as the control. RESULTS: In the laboratory, the cercariae were found in 10-, 30-, 60-cercaria subgroups in the bionic animal skin group after 1 and 2 hours, but the cercariae were found only in the 60-cercaria subgroup in the sentinel mouse group. In the simulate fields, in the water body with 5 schistosome-infected Oncomelania hupensis snails, the cercariae were found in 2 bionic animal skin devices (2/4) and 3 bionic animal skin devices (3/4) after 2 hours and 4 hours respectively, and in the water body with 10 schistosome-infected O. hupensis snails, the cercariae were found in 4 bionic animal skin devices (4/4) and 3 bionic animal skin devices (3/4) after 2 hours and 4 hours respectively in the bionic animal skin group. In the the sentinel mouse group, in the above-mentioned water bodies (with 5 or 10 schistosome-infected O. hupensis snails), the cercariae were found in 2 sentinel mice (2/4) and 1 sentinel mice (1/4) after 2 hours and 4 hours respectively; and the cercariae were found in 2 sentinel mice (2/4) and 3 sentinel mice (3/4) after 2 hours and 4 hours respectively. CONCLUSIONS: The bionic animal skin device can be used to detect the S. japonicum cercariae, and its sensibility and efficiency are superior to the traditional sentinel mouse method.

Safe burn excision prior to military repatriation: an achievable goal?

Burn excision is the gold standard treatment for full thickness and some deep partial thickness burns. Early burn excision (24-96 hours) has been shown to improve patient outcomes. However, in the military setting, transporting the patient to a centre which can provide this procedure can be delayed. Especially as control of airspace in the future may be hampered due to the political landscape. For this reason, focus on how to achieve safer burn excision prior to repatriation should be addressed. This paper considers the barriers to early burn excision in the military setting and offers potential solutions for the future.