DOI: https://doi.org/10.21203/rs.3.rs-21890/v2
Background: Self-repair of lower limb wounds has always been one of the research hotspots. Flaps and skin graft are the preferred treatment for lower extremity wound reconstruction. However, these treatments have many disadvantages, such as secondary damage, poor healing quality. In recent years, the use of acellular dermal matrix has emerged as an alternative treatment option for extremity ulcers.
Methods: This study aimed to explore whether acellular dermal matrix can be used as a single treatment to promote wound healing. 7 patients with lower extremities cutaneous deficiency exposing bone or tendon, was covered by Pelnac, which was an acellular dermal matrix product approved by China Food and Drug Administration. All the wound was treated by Pelnac without flaps and skin graft. The external dressing was changed every 10 days.
Results: After a maximum of 20 weeks, all the wounds were completely healed. During the 12 months follow-up period none of the patients developed skin wear on the treatment area. All patients maintained their postoperative ambulatory ability. All patients were satisfied with the appearance and feeling after wound healing.
Conclusion: These findings may mean acellular dermal matrix is a novel method offering opportunity for treatment of lower extremities cutaneous deficiency exposing bone or tendon. It also has the potential to close wounds of all uninfected, non-ischemic, full-thickness cutaneous deficiency.
Skin is the largest organ covering the human body. Continuity loss of normal anatomic structures and function of the skin results in a wound(1, 2). Based on the wound healing time frame, wounds are classified as acute wound or chronic. In everyday pathology wounds remain a challenging clinical problem, with early and late complications presenting a frequent cause of morbidity and mortality(3, 4). Acute wounds constitute a common health problem, with an estimated 11.8 million wounds treated in emergency departments in USA annually (5, 6). Wounds are typically characterized based on wound depth and area of skin affected(7). According to the degree of skin injury, wounds can be divided into partial-thickness wounds and full-thickness wounds(8). There are numerous therapy methods used to treat different types of wounds, such as negative pressure wound therapy, bioengineered tissue alternatives, pedicle flaps, and free tissue transfer. Based on the “Reconstruction Pyramid”, a guide for wound healing, treatments are arranged hierarchically, from minimally invasive procedures for small and superficial wounds, to highly complex procedures for large, deep, and complex soft tissue defects(9). For instance, due to a lack of redundant or pliable surrounding soft tissue, wounds in foot or ankle often need to be closed by various kinds of flaps. However, surgical flap interventions have associated disadvantages that include secondary damage, poor tissue appearance, and high operation requirements. For this reason, tissue engineered dressings have better application prospects than flap surgery. Acellular dermal matrix (ADM) is a promising method in the treatment of soft tissue defects while maintaining an enhanced quality of wound repair(10–12). In recent years, acellular dermal matrix (ADM) has been used in the treatment of deep tissue defects in combination with split-thickness skin grafts and negative pressure wound therapy(13, 14). However, ADM also has its disadvantage that it cannot achieve epithelial tissue physiological regeneration and repair independently(15). Now, we found that a porcine acellular dermal matrix can promote the complete healing of the wound.
All patients provided informed consent to participate in the study and for the use of images. We used Pelnac (an artificial dermal product approved by China Food and Drug Administration) for wound treatment. Pelnac double layer is composed of atelocollagen sponge layer and a silicone layer.
Seven patients with lower extremity cutaneous deficiency, with exposed bone or tendon, were treated in our Department from December 2014 to January 2017. This prospective study includes a 12-month follow-up, with an overall study period of 3 years. Patient age ranged between 8 and 55 years (mean age 40.6 years). None of the patients had concomitant flap or fascia flap surgery, and none presented with vascular disease or diabetes. Postoperative sensory status was evaluated through two-point discrimination and assessment of total active motion.
All surgical procedures were performed under epidural anesthesia with the patient in a supine position. A tourniquet was placed around the lower limb to limit intraoperative bleeding. After debridement and hemostasis, the wound was rinsed with H2O2 and 0.1% povidone iodine thrice. Following rinse, the wound was covered with Pelnac, following the manufacturer’s protocol. Subsequently, the Pelnac was trimmed to precisely contour to the wound, and then immersed in saline for 15 seconds before coverage. The Pelnac was sutured to the defect using 5/0 Prolene sutures. To facilitate wound exudation, small size drainage holes were made in the silicon film. The silicon film was only detached from the wound after complete healing.
Statistical analysis consists of the comparison between sick side and healthy side with two-point discrimination and total active motion, performed using the Wilcoxon signed-rank test. Statistical significance was set at P < 0.05.
In this study, 7 patients (age range, 6–62 years) were treated with Pelnac for lower extremity wounds with bone or tendon exposure (wound size range, 5–49.5 cm2). All wounds resulted from tissue removal and debridement and defects filled by suturing Pelnac in place. Final wound healing occurred within 13 weeks on average (range, 7–20 weeks) One or two linear scars were left in original wound area, dependant on wound shape. The width of scars varied 1 to 15mm depending on the initial size of wounds.
At 12 months of follow-up skin sensation and joint movement on all patients were evaluated. All patients concluded with a return to normal sensation, though slight variation in sensation between the healthy side and the affected sides was noted in a few instances. At one-year follow-up, the healed wound was free of significant pain, and range of joint motion averaged 90% of that of the healthy side (Table 1). None of the patients showed signs of skin damage or trouble walking. All persons returned to normal daily life. Specific cases can be seen in Figs. 1–3.
| Site of wound | 2-PD(mm) | VAS | TAM(%) | |||
|---|---|---|---|---|---|---|
| NO. | Uninjured side | Injured side | Patients | surgeons | ||
| 1 | Front of ankle | 13.2 | 15.2 | 8 | 9 | 90 |
| 2 | Achilles tendon area | 15.7 | 20.8 | 7 | 7 | 93 |
| 3 | Big toe | 5.4 | 7.3 | 8 | 9 | 94 |
| 4 | Achilles tendon area | 14.7 | 19.2 | 8 | 7 | 85 |
| 5 | Achilles tendon area | 19.1 | 23.9 | 7 | 7 | 84 |
| 6 | Big toe | 6.5 | 7.3 | 9 | 9 | - |
| 7 | Whole foot | 16.3 | 18.2 | 8 | 8 | 90 |
| 8 | Big toe | 6.5 | 7.2 | 8 | 8 | - |
| 9 | Big toe | 5.8 | 7.1 | 9 | 8 | - |
| 10 | Big toe | 5.4 | 7.1 | 8 | 8 | - |
| 11 | Whole foot | 15 | 19.3 | 9 | 7 | 92 |
| 12 | Whole foot | 16.1 | 18.5 | 8 | 6 | 89 |
| 13 | leg | 18 | 20.1 | 7 | 8 | 95 |
| 14 | Achilles tendon area | 15.2 | 18.1 | 7 | 9 | 85 |
| 15 | Front of ankle | 12.6 | 15.1 | 8 | 8 | 88 |
| 16 | leg | 17.6 | 19.8 | 8 | 7 | 94 |
| mean | 12.69 ± 4.99 | 15.26 ± 5.96* | 7.94 ± 0.68 | 7.94 ± 0.77 | 89.9 ± 3.8 | |
| 2-PD, two-point discrimination | ||||||
| VAS, Visual Analogue Scale/Score | ||||||
| TAM, total active motion, the percentage of movement on the affected side relative to the healthy side | ||||||
| *, p < 0.001 | ||||||
ADM has long been used as a soft tissue replacement therapy in the field of wound healing and tissue repair and reconstruction(16). Commonly, the use of ADM to repair wounds has been combined with skin graft or negative-pressure wound therapy (NPWT)(17, 18). A handful of studies indicate regeneration of full-thickness skin defects using ADM, and without skin graft or flap surgery(19–21). PELNAC, a double-layer structure of ADM, is generally used as a pretreatment before skin grafting, which can improve the survival rate of skin grafting and accelerate the wound healing(22). We once treated a case of hand trauma with a skin defect on the palm. However, the patient did not take the doctor's advice on undergoing the second skin-grafting surgery. And when he kept his next outpatient appointment with us approximately 50 days later, we found that the wound had been healed. From this, it is arguably that ADM can not only serve as an anatomical dressing, but also has the ability to stimulate wound repair. The possible mechanism of it is that ADM, which is similar to the dermal reticular structure, reduces the accumulation of collagen, induces angiogenesis and remodel the structure and function of the dermis(23).
In this article, we show that ADM can replace skin graft and flaps to promote the regeneration of full-thickness skin defects. Although the contraction of the wound cannot be completely avoided due to the poor extensibility of the skin at these injured sites, it can still be suggested that the wound is healed by regeneration. Furthermore, we found that PELNAC has certain anti-infective ability. Although at first sight, the wound appears to resemble skin necrosis or pus formation after being covered with PELNAC for a period of time, it then starts to get drier and eventually promotes the would regeneration. This is consistent with the results of our current animal experiments that the infection rate of the wound will be reduced after the use of ADM.
Compared with skin and flaps, ADM presents some distinct advantages. Firstly, patients treated with ADM are unconstrained by donor supply or damage. All volunteers do not need to take skin and flaps from other parts of the body. Secondly, although wound healing time for ADM treatment was longer than that skin graft or flaps surgery, the overall course of disease outcome was not significantly different between two therapeutic methods. We analyze the reason was that all patients treated by ADM acquired one-stage healing and did not require a second operation, thus the average time for postoperative recovery was reduced. Lastly, quality of wounds treated with ADM were better than the skin or flaps surgery arm. Comparison between afflicted and healthy limbs indicate comparable passive (or active) motion of lower limb joints. In addition, the regenerated skin was noted to heal to a fine appearance and feel.
Specimens were not sampled from healed wounds, thereby limiting further pathological analysis. However, previous work conducted at our laboratory found concomitant hair regeneration(20) for a few wounds treated with ADM(20). These rat studies showed the infiltration of stem cells following treatment, with detailed mechanism of action requiring further work.
In conclusion, for select patients, 1-stage Pelnac reconstitution can be considered as a novel method for inducing regrowth of epidermis and hair follicles, thus warranting further research.
Ethics and consent to participate
This study was approved by the Hospital Ethics Committee of the Huazhong University of Science and Technology of Tongji Medical College. All of the research processes were followed the principles outlines in the Declaration to Helsinki.
Consent for Publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Competing interests
No conflict of interest exits in the submission of this manuscript.
Funding
We gratefully acknowledge funding from the National Natural Science Foundation of China (NSFC, 81801922), Chronic Wound & Diabetes Medical Clinical Research Center Foundation of Hubei provincial China (2018BCC340) and Hubei Province key research and development program (2020BCB029, 2020BCB031).
Authors' contributions
G.L and Q.S. wrote the main manuscript text. P.Z. and H.L prepared original draft. J.H. review and editing. All authors reviewed the manuscript.
Acknowledgements
Not applicable