Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties

The treatment of chronic and non-healing wounds in diabetic patients remains a major medical problem.Recent reports have shown that hydrogel wound dressings might be an effective strategy for treating diabetic wounds due to their excellent hydrophilicity,good drug-loading ability and sustained drug release properties.As a typical example,hyaluronic acid dressing(Healoderm)has been demonstrated in clinical trials to improve wound-healing efficiency and healing rates for diabetic foot ulcers.However,the drug release and degradation behavior of clinically-used hydrogel wound dressings cannot be adjusted according to the wound microenvironment.Due to the intricacy of diabetic wounds,antibiotics and other medications are frequently combined with hydrogel dressings in clinical practice,although these medications are easily hindered by the hostile environment.In this case,scientists have created responsive-hydrogel dressings based on the microenvironment features of diabetic wounds(such as high glucose and low pH)or combined with external stimuli(such as light or magnetic field)to achieve controllable drug release,gel degradation,and microenvironment improvements in order to overcome these clinical issues.These responsive-hydrogel dressings are anticipated to play a significant role in diabetic therapeutic wound dressings.Here,we review recent advances on responsive-hydrogel dressings towards diabetic wound healing,with focus on hydrogel structure design,the principle of responsiveness,and the behavior of degradation.Last but not least,the advantages and limitations of these responsive-hydrogels in clinical applications will also be discussed.We hope that this review will contribute to furthering progress on hydrogels as an improved dressing for diabetic wound healing and practical clinical application.

The Application of Bilayer Artificial Dermis Combined with VSD Technology in Chronic Wounds

Background: Bilayer artificial dermis promotes wound healing and offers a treatment option for chronic wounds. Aim: Examine the clinical efficacy of bilayer artificial dermis combined with Vacuum Sealing Drainage (VSD) technology in the treatment of chronic wounds. Method: From June 2021 to December 2023, our hospital treated 24 patients with chronic skin tissue wounds on their limbs using a novel tissue engineering product, the bilayer artificial dermis, in combination with VSD technology to repair the wounds. The bilayer artificial dermis protects subcutaneous tissue, blood vessels, nerves, muscles, and tendons, and also promotes the growth of granulation tissue and blood vessels to aid in wound healing when used in conjunction with VSD technology for wound dressing changes in chronic wounds. Results: In this study, 24 cases of chronic wounds with exposed bone or tendon larger than 1.0 cm2 were treated with a bilayer artificial skin combined with VSD dressing after wound debridement. The wounds were not suitable for immediate skin grafting. At 2 - 3 weeks post-treatment, good granulation tissue growth was observed. Subsequent procedures included thick skin grafting or wound dressing changes until complete wound healing. Patients were followed up on average for 3 months (range: 1 - 12 months) post-surgery. Comparative analysis of the appearance, function, skin color, elasticity, and sensation of the healed chronic wounds revealed superior outcomes compared to traditional skin fl repairs, resulting in significantly higher satisfaction levels among patients and their families. Conclusion: The application of bilayer artificial dermis combined with VSD technology for the repair of chronic wounds proves to be a viable method, yielding satisfactory therapeutic effects compared to traditional skin flap procedures.

Double-nylon purse-string suture in closing postoperative wounds following endoscopic resection of large(≥3 cm)gastric submucosal tumors

BACKGROUND Endoscopic full-thickness resection(EFTR)of gastric submucosal tumors(SMTs)is safe and effective;however,postoperative wound management is equally important.Literature on suturing following EFTR for large(≥3 cm)SMTs is scarce and limited.AIM To evaluate the efficacy and clinical value of double-nylon purse-string suture in closing postoperative wounds following EFTR of large(≥3 cm)SMTs.METHODS We retrospectively analyzed the data of 85 patients with gastric SMTs in the fundus of the stomach or in the lesser curvature of the gastric body whose wounds were treated with double-nylon purse-string sutures after successful tumor resection at the Endoscopy Center of Renmin Hospital of Wuhan University.The operative,postoperative,and follow-up conditions of the patients were evaluated.RESULTS All tumors were completely resected using EFTR.36(42.35%)patients had tumors located in the fundus of the stomach,and 49(57.65%)had tumors located in the body of the stomach.All patients underwent suturing with double-nylon sutures after EFTR without laparoscopic assistance or further surgical treatment.Postoperative fever and stomach pain were reported in 13(15.29%)and 14(16.47%)patients,respectively.No serious adverse events occurred during the intraoperative or postoperative periods.A postoperative review of all patients revealed no residual or recurrent lesions.CONCLUSION Double-nylon purse-string sutures can be used to successfully close wounds that cannot be completely closed with a single nylon suture,especially for large(≥3 cm)EFTR wounds in SMTs.

Mesenchymal stem cell-derived extracellular vesicles in skin wound healing:roles,opportunities and challenges

Skin wounds are characterized by injury to the skin due to trauma,tearing,cuts,or contusions.As such injuries are common to all human groups,they may at times represent a serious socioeconomic burden.Currently,increasing numbers of studies have focused on the role of mesenchymal stem cell(MSC)-derived extracellular vesicles(EVs)in skin wound repair.As a cell-free therapy,MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy.Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures,including the regeneration of vessels,nerves,and hair follicles.In addition,MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization,wound angiogenesis,cell proliferation,and cell migration,and by inhibiting excessive extracellular matrix production.Additionally,these structures can serve as a scaffold for components used in wound repair,and they can be developed into bioengineered EVs to support trauma repair.Through the formulation of standardized culture,isolation,purification,and drug delivery strategies,exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair.In conclusion,MSCderived EV-based therapies have important application prospects in wound repair.Here we provide a comprehensive overview of their current status,application potential,and associated drawbacks.

ROS Balance Autoregulating Core-Shell CeO_(2)@ZIF-8/Au Nanoplatform for Wound Repair

Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.

ON101 Cream Increases the Wound Healing Rate in Diabetic Patients with Uremia—Cases Report

Diabetic patients who underwent long-term dialysis may increase the prevalence of foot ulceration. In addition, diabetic foot ulcer (DFUs) patients with end-stage renal disease (ESRD) do not heal well, and the amputation rate is 6.5 - 10 times higher compared to the non-nephropathic diabetic population. Thus, a suitable therapeutic agent was needed. ON101 is a topical cream that promotes diabetic wound healing through a unique macrophage-regulating ability. In this case series, we included 5 diabetes patients (mean age 54.6 ± 8.7 years, 4 mal) with ESRD (mean eGFR 7.4 ± 3.35 mL/min/1.73m2) and had experienced dialysis for at least 4.5 years. These patients also have UT (University of Texas) grade 2A DFUs that have existed for at least 1.5 months (mean ulcer duration 8.3 ± 8.97 months). These subjects were applied ON101 twice daily for up to 20 weeks, and wound size was recorded during treatment. Among these subjects, three ulcers (patient No. 1, 2, and 3) completely healed within 10 weeks upon ON101 application, and one ulcer was 99% reduced at 20th weeks (patient No. 4). Only one ulcer didn’t show an obvious response that may due to poor compliance in wound care and glucose control. In summary, the overall healing rate was 60%, suggesting ON101 performed equivalence healing efficacy in dialysis patients compared with those who did not have dialysis.

Regulatory T cells in skin regeneration and wound healing

As the body’s integumentary system,the skin is vulnerable to injuries.The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality.To this end,multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue.Such temporally-and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation.In this context,regulatory T cells(Tregs)hold a key role in balancing immune homeostasis and mediating cutaneous wound healing.A comprehensive understanding of Tregs’multifaceted field of activity may help decipher wound pathologies and,ultimately,establish new treatment modalities.Herein,we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair.Further,we discuss how Tregs operate during fibrosis,keloidosis,and scarring.

Transplantation of a pectoralis major flap for the repair of myiasis wounds

Myiasis is a disease caused by the invasion and colonization of human tissues and organs by the larvae of flies.This is manifested by the formation of necrotic tissue in the lesion,the colonization of fly eggs and the spread of fly larvae.This disease is mostly found in areas with poor sanitary conditions.Poor wound care,necrotic tissue formation,reduced immunity,and frequent contact with flies are risk factors for this disease.Myiasis can be divided into obligate and facultative parasitism,^([1])while some scholars have classified myiasis according to its location.^([2])In addition,some cases of myiasis are secondary to wound infection or poor surgical maintenance.^([3,4]).

High-strength antiswelling adhesive achieves both hemostasis and wound healing

Skin is one of the most vulnerable tissues,but there is a lack of injectable bioactive hydrogel dressings,which possess high strength,antiswelling capacity,and wet tissue adhesiveness,but also a rapid gelling process to enable rapid hemostasis,sutureless wound closure,and scarless healing of infected skin wounds[1e5].A new injectable,antibacterial,and multifunctional hydrogel dressings based on poly(citric acid-co-polyethylene glycol)-g-dopamine(PCPD)and amino-terminated Pluronic F127(APF)mi-celles loaded with astragaloside IV(AS)was developed for this pur-pose,as shown in Fig.1A[6].

Platelet-rich plasma treatment for chronic wounds:A case report and literature review

BACKGROUND Wound healing is a complicated process that can be heavily influenced by patient comorbidities,in some cases leading to a chronic non-healing wound.Evidence presented in the medical literature supporting the clinical use of autologous platelet-rich plasma(PRP)in treatment of such wounds is becoming increasingly compelling.Mechanisms involved include complex interactions between the patient’s thrombocytes,cytokines,and growth factors.CASE SUMMARY We present a case of a 72-year-old male patient with a long-standing chronic wound and multiple comorbidities.Over the course of more than 7 months,the patient was unsuccessfully treated with all routinely used measures,including different dressing approaches.Multiple antibiotic regimens were administered for wound infection,with repeated evaluation of microbiological swab results.Finally,after three PRP applications,the wound showed clinical improvement with complete restitution of the epithelial layer of the skin.CONCLUSION PRP treatment may be beneficial to reduce healing time in chronic wounds.

A Skin-Inspired Self-Adaptive System for Temperature Control During Dynamic Wound Healing

The thermoregulating function of skin that is capable of maintaining body temperature within a thermostatic state is critical.However,patients suffering from skin damage are struggling with the surrounding scene and situational awareness.Here,we report an interactive self-regulation electronic system by mimicking the human thermos-reception system.The skin-inspired self-adaptive system is composed of two highly sensitive thermistors(thermal-response composite materials),and a low-power temperature control unit(Laserinduced graphene array).The biomimetic skin can realize self-adjusting in the range of 35–42℃,which is around physiological temperature.This thermoregulation system also contributed to skin barrier formation and wound healing.Across wound models,the treatment group healed~10%more rapidly compared with the control group,and showed reduced inflammation,thus enhancing skin tissue regeneration.The skin-inspired self-adaptive system holds substantial promise for nextgeneration robotic and medical devices.

Eyelid Wounds: Epidemiological, Clinical and Etiological Aspects

Purpose: The aim is to show epidemiological, clinical and etiological characteristics of palpebral wounds. Methodology: This was a retrospective study focusing on patients with an eyelid wound, over a 10-year period from 2012 to 2021. We collected and analyzed the data using Excel. Results: The frequency of eyelid wounds was 0.1%. The average age of our patients was 19.38 years with a range of 1 and 62 years. The sex ratio was 3.7. Eighty-one percent of patients lived in Dakar. Fifty-seven percent (57%) of patients consulted less than 24 hours after the trauma and 7% of patients on D1. The circumstances were brawls (11%), domestic accidents (9%), road accidents (6%), and work accidents (6%). We noted 1 case of dog bite. Thirteen patients presented with post-traumatic decreased visual acuity. Involvement of the isolated upper eyelid was noted in 40% of cases and both eyelids in 15% of cases. Involvement of the lacrimal ducts was noted in 17% of cases, and that of the free edge in 21% of cases. Eyelid wounds were associated with eyeball damage in 21% of cases. Various associated lesions were observed. Ninety-one percent of patients received surgical treatment. Three cases of superinfections, 1 case of conjunctival granuloma and 1 case of phthysis of the eyeball with postoperative retinal detachment were noted. Conclusion: Eyelid sores are relatively common in our context. They require rapid surgical treatment in order to preserve the functional and aesthetic prognosis. .

Antimicrobial,antibiofilm,angiogenesis,anti-inflammatory,and wound healing activities of zinc nanoparticles green synthesized using Ferula macrecolea extract

Objective:To assess the antimicrobial,antibiofilm,anti-inflammatory,angiogenic,and wound healing activities of zinc nanoparticles(ZNPs)green synthesized using Ferula macrecolea extract.Methods:The green synthesis was conducted using the precipitation method.Then,the minimum inhibitory concentration(MIC),minimum bactericidal concentration(MBC),and minimum biofilm inhibition concentration 50%(MBIC50)of ZNPs against Staphylococcus aureus(S.aureus)and Pseudomonas aeruginosa(P.aeruginosa)were evaluated.The effects of ZNPs on the gene expressions of Staphylococcus spp.[intracellular adhesion A(icaA)and D(icaD)]and P.aeruginosa(rhlI and rhlR)were investigated using quantitative real-time PCR.In addition,the effects of ZNPs on wound healing,angiogenesis,and anti-inflammatory markers were assessed.Results:The green-synthesized ZNPs demonstrated significant antimicrobial efficacy against S.aureus and P.aeruginosa.The biofilm formation in S.aureus and P.aeruginosa was also inhibited by ZNPs with MBIC50 values of 3.30μg/mL and 2.08μg/mL,respectively.Additionally,ZNPs downregulated the expression of biofilm-related genes icaA,icaD,rhlI,and rhlR in the tested bacteria.They also demonstrated promising in vitro wound healing effects by promoting fibroblast cell proliferation and wound closure in a dose-dependent manner.A significant increase in the expression of HLA-G5 and VEGF-A genes as well as a marked decrease in the expression of NF-κB,IL-1β,and TNF-αgenes were observed in cells treated with ZNPs compared to the control group(P<0.05).Conclusions:ZNPs display promising antibacterial effects against S.aureus and P.aeruginosa and wound-healing effects by inhibiting biofilm formation,inducing angiogenesis,and reducing inflammation.However,further studies must be conducted to specify the accurate mechanisms of action and toxicity of ZNPs.

Multifunctional hydrogel combined with electrical stimulation therapy for promoting diabetic wound healing

Diabetic wounds, as a complication of diabetes, are slow to heal and seriously affect the quality of life of patients. Functional hydrogel dressing is an effective approach to improve diabetic wound healing. Electrical stimulation (ES) therapy is conducive to promoting cell migration and wound healing. In this work, a multifunctional PPTZ hydrogel wound dressing was developed by freeze-thaw method with polyvinyl alcohol (PVA), phytic acid (PA), tannic acid (TA), and Zinc chloride. The obtained PPTZ hydrogel has good mechanical properties (stress and strain of 700.03 kPa and 575.08%), light transmittance (close to 100%) and antibacterial rate (over 75%). With good biocompatibility, antioxidant abilities and conductivity, the PPTZ hydrogel could effectively promote the healing of diabetic wounds with two weeks under the action of electric field, which provides an auxiliary treatment strategy for diabetic patients.

Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing

Delayed and nonhealing of diabetic wounds imposes substantial economic burdens and physical pain on patients.Mesenchymal stem cells(MSCs)promote diabetic wound healing.Particularly when MSCs aggregate into multicellular spheroids,their therapeutic effect is enhanced.However,traditional culture platforms are inadequate for the efficient preparation and delivery of MSC spheroids,resulting in inefficiencies and inconveniences in MSC spheroid therapy.In this study,a three-dimensional porous nanofibrous dressing(NFD)is prepared using a combination of electrospinning and homogeneous freeze-drying.Using thermal crosslinking,the NFD not only achieves satisfactory elasticity but also maintains notable cytocompatibility.Through the design of its structure and chemical composition,the NFD allows MSCs to spontaneously form MSC spheroids with controllable sizes,serving as MSC spheroid delivery systems for diabetic wound sites.Most importantly,MSC spheroids cultured on the NFD exhibit improved secretion of vascular endothelial growth factor,basic fibroblast growth factor,and hepatocyte growth factor,thereby accelerating diabetic wound healing.The NFD provides a competitive strategy for MSC spheroid formation and delivery to promote diabetic wound healing.

Self‑Healing Dynamic Hydrogel Microparticles with Structural Color for Wound Management

Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances.It is vital to develop multifunctional hydrogel dressings,with well-designed morphology and structure to enhance flexibility and effectiveness in wound management.To achieve these,we propose a self-healing hydrogel dressing based on structural color microspheres for wound management.The microsphere comprised a photothermal-responsive inverse opal framework,which was constructed by hyaluronic acid methacryloyl,silk fibroin methacryloyl and black phosphorus quantum dots(BPQDs),and was further re-filled with a dynamic hydrogel.The dynamic hydrogel filler was formed by Knoevenagel condensation reaction between cyanoacetate and benzaldehyde-functionalized dextran(DEX-CA and DEX-BA).Notably,the composite microspheres can be applied arbitrarily,and they can adhere together upon near-infrared irradiation by leveraging the BPQDs-mediated photothermal effect and the thermoreversible stiffness change of dynamic hydrogel.Additionally,eumenitin and vascular endothelial growth factor were co-loaded in the microspheres and their release behavior can be regulated by the same mechanism.Moreover,effective monitoring of the drug release process can be achieved through visual color variations.The microsphere system has demonstrated desired capabilities of controllable drug release and efficient wound management.These characteristics suggest broad prospects for the proposed composite microspheres in clinical applications.

Macrophages:Key players in diabetic wound healing

In this editorial,we discuss the article by Wen et al published.Diabetic foot ulcers are prevalent and serious complications of diabetes,significantly impacting patients’quality of life and often leading to disability or death,thereby placing a heavy burden on society.Effective diabetic wound healing is hindered by an imbalance in macrophage polarization;many macrophages fail to transition from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,which is crucial for tissue remodelling and repair.The wound healing process is both dynamic and complex.Healthy M1 macrophages,which have strong phagocytic abilities,are vital during the inflammatory phase of diabetic wound healing.However,the failure to transition to M2 macrophages during the proliferative phase hinders wound healing.We anticipate the development of new therapies that can repair damaged M1 macrophages during the inflammatory phase and promote M2 macrophage polarization during the proliferative phase,thereby enhancing the overall healing process.

Study on the effect of Shixiang plaster on the expression of CD31,serum FN,and VEGF in a rat model with chronic wounds

Background:Chronic wounds pose a significant surgical challenge,often requiring traditional treatments with limited efficacy.This study explores the promising impact of Shixiang plaster,a classic Chinese ointment,on wound healing.We investigated the cluster of differentiation 31(CD31)expression,serum fibronectin(FN),and vascular endothelial growth factor(VEGF)levels in SPF rats with induced wounds to elucidate the mechanism behind Shixiang plaster’s effectiveness.We investigated the effect and explored the role of Shixiang plaster on the expression of CD31,serum FN,and VEGF in chronic wounds.Methods:The study involved 36 SPF rats divided into model,rb-bFGF,and Shixiang plaster groups.Penicillin was injected into the rats before modelling for 3 days to prevent infection.The skin was excised 2 cm below the horizontal line of the inferior border of the shoulder bone in the middle of the rat column up to the deep fascial layer and inoculated with a certain concentration of Staphylococcus aureus;the wound was covered aseptically for 3 days.The trauma area of the rats was observed at 3,7,and 14 days,respectively.Histopathology was observed using haematoxylin eosin and Masson staining.CD31 expression was detected using immunohistochemistry staining.FN and VEGF expression was detected using serum ELISA.Statistical analyses were carried out by the method of SPSS.Results:Regarding wound morphology,at 3 days,the recovery area of the Shixiang plaster group was larger than that of the other two groups,at 7 days,the wound healing rate of the Shixiang plaster group was significantly higher,and at 14 days,the wounds of the Shixiang plaster group had been mostly healed,with a healing rate of 98.3%.Haematoxylin eosin staining revealed a large amount of granulation tissue at 3 days in the Shixiang plaster group,and the epidermal scales disappeared at 14 days,with thinner epidermal thickness at 1 lesion and a large reduction in inflammatory cell infiltration.Masson staining showed that at 3,7,and 14 days,blue staining was the most abundant and deeper in the Shixiang plaster group,with richer collagen and a compact tissue matrix.Immunohistochemical testing showed strong positive expression of CD31 in the Shixiang plaster group,with abundant neovascularisation and large official lumens extending towards the surface of the wound.Statistically significant elevated expression of FN at 7 and 14 days was determined by ELISA in the Shixiang plaster group,and VEGF expression was significantly increased at 7 days,but expression had been expressed at a low level at 14 days.Conclusion:Shixiang plaster exhibits remarkable efficacy in healing chronic wounds.The proposed mechanism involves FN’s promotion of angiogenesis and cell proliferation,VEGF’s impact on angiogenesis and inflammation,and CD31’s regulatory role in inhibiting inflammation while promoting angiogenesis.

Nanoskin®-ACT—The Impact of Natural Membrane & Soft with Chronic and Untreated Wounds

Bacterial cellulose (BC) is a versatile biomaterial with unique properties that make it promising for various biomedical applications, including wound healing. The extracellular matrix (ECM) plays a crucial role in wound healing, providing a structural scaffold and signaling cues for cell migration and proliferation. This study investigates the potential of BC as a scaffold for ECM production and its effect on in vivo wound healing. In this work, the bacterial cellulose fermentation process is modified by the addition of Green Propolis and Usnic acid to the culture medium and natural materials before the bacteria are inoculated. In vivo behaviour using natural membranes for regenerative medicine is presented and it is in edit. Overall, our findings demonstrate the potential of BC as a scaffold for ECM production and its beneficial effects on in vivo wound healing. BC-based dressings may offer a novel approach to promoting wound healing and tissue regeneration in clinical settings. Further studies are warranted to optimize BC-based therapies and explore their full potential in regenerative medicine.

The Impact of Psychosocial Influences on Chronic Wound Healing

This comprehensive review explores the intricate dynamics between psychosocial factors and chronic wound healing processes, specifically focusing on prevalent conditions such as pressure ulcers, diabetic foot ulcers, and venous leg ulcers. By examining the roles of psychiatric conditions, including depression, anxiety, and post-traumatic stress disorder (PTSD), this paper illuminates how these factors intricately influence wound healing dynamics, including mechanisms of pain perception and inflammatory responses. Furthermore, we evaluate the effectiveness of integrated biopsychosocial interventions, which encompass a holistic approach to wound care, thereby enhancing healing outcomes for dermatology patients. Future studies should focus on investigating the specific psychosocial determinants that significantly influence wound healing, exploring novel therapeutic strategies, and implementing personalized interventions to meet the unique needs of each patient. Such endeavors hold promise in advancing the fields of psychodermatology and wound management, fostering a deeper understanding and application of psychosocial considerations in dermatological care.