Spincare System Demonstrates Safety and Efficacy in Treating Partial-Thickness Burns

Abstract Partial-thickness burns are the most common form of burns, affecting the dermis and possibly resulting in scarring and infection. The Spincare System is a new device that uses electrospinning technology to create a temporary skin-like matrix that can be applied to wounds. This study evaluated the performance, safety, and efficacy of Spincare in treating superficial to partial-thickness burns not considered for surgery. A prospective single-arm, open-label, multicenter study was conducted in 3 adult burn units across Israel. Forty-four patients with superficial to intermediate burns of up to 10% of TBSA were enrolled. Spincare was applied to the wounds, and follow-up visits were performed on days 7, 14, and 21 and months 3 and 6 posttreatment. Thirty-one patients with 36 wounds completed the day 21 visit. The mean wound healing area on day 21 was 97.26 ± 9.41%, and the mean healing time was 12.8 ± 4.3 days. Only one moderate adverse event was observed concerning the treatment, and it is important to acknowledge the potential progression of this hypertrophic scar into a keloid. This study demonstrated that Spincare is a safe and effective device for treating superficial to intermediate partial-thickness burns. Spincare achieved rapid and complete wound healing with a low incidence of adverse events.


INTRODUCTION
Burn wound healing involves a well-organized, complex process that leads to the repair of injured tissues. 1,2The severity of burn injuries dramatically varies, and morbidity and mortality tend to increase as the surface area of burns increases. 3Generally, burn wounds of partial-thickness that are appropriately managed show measurable progress and closure within 2-3 weeks.Current appropriate medical practice for full-thickness burns is the early excision and coverage with skin grafts or substitutes.For partial-thickness burns, burn clinicians are faced with whether to excise the burn or leave it for primary healing, having implications for scarring that represent a significant health burden and drain on resources, contributing to a substantial disability, morbidity, and cost. 4evice technology in wound care has progressed substantially over the recent decades, helping to revolutionize how clinicians approach wound management. 5As the industry continues to develop new technologies and refine existing ones, we can expect to see more innovative solutions.Burn care has progressed from labor-intensive painful dressings to intelligent dressings requiring less intervention. 6Today, device technology plays an increasingly important role in wound care, offering new and innovative ways to promote healing and prevent infection. 7ne such technology is electrospinning, a novel technology that can treat wounds. 8The electrospun nanofibrous polymer-based matrix, which is applied to the wound bed, consists of a thin, flexible film that spun out of a solution of polymers.The electrospun solution creates, in situ, a uniform, steady stream of nanofibers that deposits on the wound.The electrospinning process creates a nanofibrous polymer-based matrix with properties ideal for wound care, mimicking the extracellular matrix structure, and providing temporary skin-like protecting coverage to the wound. 9Electrospun nanofibers have not only been preclinically tested using animal wound healing models 8 but also have been used in donor sites and found to be safe and effective. 9Here, we evaluated the performance, safety, and efficacy of the Spincare System and matrix in managing superficial to intermediate partial-thickness burns.

Study design
A prospective, single-arm, open-labeled multicenter study for treating partial-thickness burns (not considered for surgery) was performed to evaluate the effectiveness and safety of the Spincare System, representing a bedside electrospinning device that applies a nanofibrous matrix that mimics the structure of the extracellular matrix and thereby enhances fibroblast adhesion and proliferation (Spincare System, Nanomedic Technologies Ltd.).
The enrollment took place from March 2017 to August 2021.Recruitment was performed in 3 departments of plastic and reconstructive surgery in the following medical centers in Israel: Sheba Medical Center (Ramat-Gan), Rambam Health Care Campus (Haifa), and Sourasky Medical Center (Tel-Aviv).
The study included screening patients, 6 clinic visits, and unscheduled visits conducted as necessary.During the screening, patients were examined to determine their burn wound classification.All patients considered eligible for study participation received the Spincare matrix according to the Spincare instructions for use on the patient's day 1 of the study.Follow-up visits were performed on days 7, 14, and 21 posttreatment, during which the matrix could be maintained, removed, or replaced as per the Principal Investigator's (PI) decision.The extended follow-up visits were conducted 3 and 6 months posttreatment.

Ethics
The study was conducted according to the good clinical practice (GCP) guidelines as described in the 21 Case Report Form 812.28(a)(1),ISO 14155:2020, and ICH GCP Guideline (amended in 2016) documents.Also, the Declaration of Helsinki (7th revision 2013) and all applicable regulatory requirements, including local requirements per the Israeli Ministry of Health, were followed.Furthermore, the Ethics Committee approvals for the study, the patient information sheet, and the consent form were required before the study began.
The Institutional Review Board of each contributing center approved the study protocol following the Helsinki Declaration, and written consent was obtained from each participant before participating in the study.The Israeli Ministry of Health also approved the current study.This trial was registered at ClinicalTrials.gov as NCT02997592 (https:// clinicaltrials.gov/ct2/show/NCT02997592).

Patients
To be included in this study, patients had to meet all the inclusion criteria and none of the exclusion criteria.The inclusion criteria included ≥18 years old of both sexes with partialthickness burn wounds (superficial to intermediate) of up to 10% of the TBSA, of which the target wound for treatment is up to 5% TBSA or up to 300 cm 2 .In addition, patients had to present at the emergency room within the first 24-48 hours postinjury and have their wounds debrided.Finally, all patients had to give written informed consent before enrolling in the study.
Exclusion criteria included any known systemic infection, malignancy, major systemic disorder (hepatic, renal, neurologic, or endocrinologic disorders), dermatological disorders (psoriasis, pemphigus, Steven Johnson), psychiatric conditions, burns greater than specified above, full-thickness burns as well as pregnant or nursing females.In addition, patients with electrical or chemical burns were excluded.Finally, patients participating in another clinical trial within 30 days before the screening visit were excluded.

Outcome measures
Our 2 primary outcomes were effectiveness and safety.The effectiveness was measured as wound healing and re-epithelialization up to day 21, where the burn was considered healed when at least 95% of the total area was re-epithelialized and no dried serous exudate was evident.
The number of healed wounds on day 21 was cumulative, that is, wounds that already healed up to day 21 were counted on day 21 even if complete healing (re-epithelialization ≥95%) was obtained on day 7 or day 14 or during an unscheduled visit performed up to day 21.The safety was measured using the Draize Dermal Irritation Scoring system (DDIS) described elsewhere. 10econdary outcomes included several indices: pain assessment (using the Visual Analog Scale (VAS) scale at rest, during the Spincare matrix application, and postapplication), itching (using the VAS scale at 3 and 6 months), scarring (using the Vancouver Scar Scale at 3 and 6 months), percent of patients with infection, time of application (using numerical rating scale), and ease of use (using 0-5 numerical rating scale).
In addition, adverse events (AE) were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 19.1 (or higher) terminology and presented in tables by System Organ Class (SOC) and Preferred Term (PT).The AE data were listed individually, and the frequency of device-related AE was summarized in tables by SOC, PT, and seriousness.

Statistical analysis
All measured variables and derived parameters were listed individually and, if appropriate, tabulated by descriptive statistics.In addition, for categorical variables, summary tables were provided, giving sample size and absolute and relative frequency.Summary tables were provided for continuous variables, giving sample size, arithmetic mean, standard deviation, median, minimum, and maximum.All data were analyzed using SPSS Version 25 or Stata 16.

Primary outcome-effectiveness
Effectiveness was assessed as the number (percent, %) of wounds healed, where a wound was considered healed if re-epithelization was ≥95% of the total wound area.A cumulative number of 10/42 (23.8%), 31/38 (81.6%), and 35/38 (92.1%) wounds were considered healed up to days 7, 14, and 21, respectively (Table 2).The healing was subsequently examined at follow-up months 3 and 6 and found to be 38/38 (100%, of which 26 were intermediate wounds and 12 were superficial wounds) at both time points.
The mean healing time was 12.8 ± 4.3 days, and examples of typical healing processes can be seen in Figures 1-3.

Secondary outcome-pain
The pain was assessed using the VAS from 1 to 10, where 0 indicates no pain and 10 indicates the worst pain experienced.The results are shown in Table 4. On procedure day 1, the mean VAS score during the procedure was 2.94 ± 2.93, compared to 2.50 ± 3.02 and 1.27 ± 2.07, preand postprocedure, respectively.On redressing visits, the VAS score was 4.53 ± 3.87 during the procedure, with a pain score of 3.00 ± 3.38 postprocedure (Table 4).

Secondary outcome-itching
The itching was assessed based on a VAS from 1 to 10, where 10 indicates the worst experience.Table 5 presents the itching scores assessed on days 7, 14, and 21 and follow-up months 3 and 6.

Secondary outcome-scarring
The total Vancouver Scar score was calculated as the sum of the 4 variables scores assessed: vascularity, height/thickness, pliability, and pigmentation (can reach 13 when all variables are at max).The total score was at the lower value of the Vancouver Scar Scale for all wounds (2.13 ± 2.45 and 2.00 ± 2.34 at month 3 and month 6, respectively) and less for superficial than intermediate wounds (Table 6).

Secondary outcome-AE
A summary of AE is presented in Table 7.A total of 17 AEs occurred in 13 out of 31 patients; one had 2 AEs.Of 17 AEs, 15 (88%) were mild, 1 moderate, and 1 severe.Fifteen AEs, including the severe one, were assessed as unrelated to the treatment.Furthermore, one minor occurrence (pain at the site of application) was determined to be "probably unrelated," and one moderate adverse event-hypertrophic scar-was deemed to be "possibly related."At the time of assessment, we were aware that this hypertrophic scar could potentially be a keloid.However, it was still challenging to differentiate between the two.

Secondary outcome-ease of use and time of dressing
In most wounds, the Spincare matrix was applied once and left on the wound throughout the healing process.In those cases, the matrix peels off on its own once healing is complete underneath.Thirteen subjects underwent redressing in addition to the first treatment; 3 of them underwent redressing twice, that is, a total of 16 redressing cases were recorded for 14 wounds, representing 27% occurrence of redressing.The total number of 68 dressing applications to our patients using the Spincare System was evaluated, and a vast majority of them (~84%) reported it as "easy to apply"; only ~10% found the application of dressing by the Spincare System "moderate" or "hard to apply" (Table 8).Accordingly, 77% of the treatments could apply the matrix using the Spincare System in less than 10 min and 97% in less than 20 min.It took more than 20 min for only 3% of dressing applications (Table 8).

DISCUSSION
This study evaluated the use of the Spincare System in managing partial-thickness burns and demonstrated effectiveness and safety with a sound healing process, healing time, and long-term results with high-quality scarring without complications.The study was observational, without internal controls, where all patients received dressing by the Spincare System.As such, we discuss our results in the context of published work investigating the use of other comparable dressings in partial-thickness burn management.
In their 4-year experience, Blome-Eberwein et al assessed healing outcomes and complications using an absorbable synthetic membrane (a synthetic skin substitute), Suprathel, to treat partial-thickness burns. 11The authors reported that the average time to heal was 13.7 days for ≥90% epithelialization, with 11.9 days for pediatric patients and 14.7 days for adults.In addition, the average pain level was 1.9 (2.7 for adults) throughout the treatment period on a 10-point scale.Applying the same healing criteria (≥90%) to our data (adult patients) indicated a shorter average healing time of 11.3 ± 3.8 days for our adult population treated with the Spincare System, indicating a shorter average healing time of approximately 3 days, which is on par with the healing of pediatric patients reported by Blome-Eberwein et al. 11 Overall, the pain level associated with the Spincare System treatment was relatively low, with our study demonstrating lower pain levels measured during procedure days and even follow-up visits.These results indicated that the Spincare System might improve the healing process in adult patients.Substantially, infection is a common and significant risk factor in burn healing; only a single case of infection (~2% of the cohort) was noted in our patients, which, in addition, was unrelated to the Spincare matrix.Blome-Eberwein et al reported a more than 4 times higher proportion of infections (8.79%) in their adult cohort of patients. 11nother study by Highton et al examined Suprathel for partial-thickness burns in children and found that ~70% of their patients were healed at 21 days postinjury, 12  than our results in adults presented here using the Spincare System (~92%).The authors also reported that the healing time of superficial partial-thickness and mid-dermal burns was similar, 12 aligns with our results.

much less
Franck David et al compared the performance of a soft silicone-coated wound contact layer (Mepitel One) with a lipid-colloid dressing (UrgoTul) in treating acute wounds in adult patients. 13These patients presented with an acute wound of traumatic origin (dermabrasion, skin tears, other) or a benign superficial thermal burn (less than 10% of total body surface) requiring dressings.The wound size was between 3 and 240 cm 2 .The authors reported a complete wound healing (100% re-epithelialization) by day 21 in ~66% of patients (39/59 patients) in the Mepitel group and ~44% of patients (27/62 patients) in the UrgoTul group. 13In this context, our data showed 81% healing (31/38 wounds) when applied the same criterion (100% re-epithelialization by day 21).Overall, the Spincare System provides comparable or better support for short-term healing processes than other commercially available dressing options for treating partial-thickness burns.
5][16] Some significant risk factors for keloid formation include age under 30 and family history. 17It is important to note that a keloid differs from a hypertrophic scar. 15f a tendency to form keloids is known, some preventive steps could be taken, such as applying a pressure pad or a silicone gel pad for 6 months after a skin injury, though this does not represent a standard of care for burn injuries. 18In our study, only one patient (~2% of the total cohort) treated with the Spincare System matrix presented with a keloid formation, as opposed to ~14% of patients who received topical treatment with the Suprathel membrane as reported by Blome-Eberwein et al. 11 Our one case of keloid formation was also reported as the only adverse event possibly associated with the Spincare matrix, indicating good safety properties of the system.In addition, most of our clinical personnel found the Spincare System easy to use and could complete the dressing in less than 10 min.This provides much better comfort to patients and shorter exposure of wounds to the environment, reflected in relatively low pain levels and minimal infections.
This study demonstrated the advantages of Spincare beyond the study endpoints worth addressing.The matrix showed excellent adherence on all wounds, even in hard-to-heal areas such as hands and shoulders; this potentially makes the dressing phase much quicker and easier for the hospital team.The matrix remained on the wound through the healing period and peeled off when full epithelization was achieved.This, in turn, allowed us to avoid secondary dressing in a very early stage, which sequentially allowed the freedom to move, maintenance of a range of motion and no loss of function, early start of physiotherapy and regular showers, potentially contributing to patients' quality of life in this challenging period.
Finally, our study was conducted in a real-world clinical environment.As such, this design inherently includes a limitation, as no internal control was involved.However, we were able to compare our results with already published

CONCLUSION
Current findings indicate that using the Spincare System in managing partial-thickness burns is safe and effective while suggesting advantages such as excellent adherence, ease of use in a hard-to-dress area, early removal of secondary dressings, and early showers.Spincare achieved rapid and complete wound healing with a low incidence of AE.

Figure 1 .
Figure 1.Fifty-Four-Year-Old Male, Right-Hand Superficial to Intermediate Partial-Thickness Burn (A) Treated With Spincare Matrix (B) 24 h Postinjury and Posthypochlorite Solution and Blister Debridement.Smooth Healing Process (C-E) and Complete Healing Achieved by Day 14 With No Infection or Other Complication.Excellent Adherence Allowed Free Use of the Hand and Early Start of Exercise.Excellent Scarring Was Observed at 6 months (F).

Figure 2 .
Figure 2. Forty-Two-Year-Old Male With Superficial Partial-Thickness Burn on the Left Shoulder, Proximal Arm, and Lower Back (A).A Spincare Matrix Was Applied on Admission and Posttreatment With a Hypochlorite Solution.Spincare Was Easily Applied to This Overly Complicated Area to Dress.Excellent Adherence Allowed the Immediate Start of Physiotherapy and Showers.Healing Progress on Day 7 (B) and Complete Healing by Days 14 and 21 (C, D) With Excellent Scarring at 6 months (E).

Figure 3 .
Figure 3.A 60-Year-Old Female With Partial-Thickness Burns Hot Water in the Lateral Area of the Left Thigh (A).Spincare Applied on Admission (B).Healing Progress on Day 7 (C) and Complete Healing by Days 14 and 21 (D, E) With Excellent Scarring at 6 months (F).

Table 1 .
Patient Enrollment and Clinical Characteristics

Table 2 .
Cumulative Percent of Healing Wounds a a Note that cumulative numbers are taking in account wounds healed up to the respective follow-up visit.b Wound healing considered complete at ≥95% re-epithelization

Table 3 .
Evaluation of Dermal Safety in Wounds Treated With the Spincare System

Table 4 .
Pain Assessment Pre, During, and Post-procedure using the Spincare System

Table 5 .
Itching Assessment of Wounds Treated with the Spincare System

Table 6 .
Scarring Assessment of Wounds Treated with the Spincare System using the Vancouver Scar Scale

Table 7 .
Summary of Adverse Events by SOC and PT Recorded in Patients Treated with the Spincare System

Table 8 .
Assessment of the Ease of Use of the Spincare System