Granulation-Embedded Autologous Skin Grafting Improves Healing Chronic Wounds at High Altitudes: A Pilot Study

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Chronic wounds are long-lasting wounds that fail to achieve complete anatomical and functional repair or re-epithelialization through the normal healing process after 1 month of clinical treatment.¹ Chronic wounds are characterized by complex pathogenesis and long disease courses, which may be associated with the long-term excessive inflammatory response,² the persistence of bacterial biofilms, decreased angiogenesis, and insensitivity to repair stimulation, finally resulting in high disability rates.^3-4 It is estimated that approximately 10 million patients in the world suffer from chronic wounds.⁵ The long disease course and high disability rates of chronic wounds are not only associated with poor quality of life but also incur a high health care burden.⁶

Over recent decades, surgery has been used as the main treatment for chronic wounds, including procedures such as debridement, skin grafting, or the use of local flaps.^7-8 In stamp skin grafting, the edematous granulation tissue is removed and the skin graft is placed on the normal tissue base. However, the stamp skin is easily removed from the surgical area during dressing changes in the early postoperative period. Local flap repair requires the use of adjacent or distant healthy tissue to cover the wound, and it has high requirements for local medical conditions and surgical skills. Moreover, both stamp skin grafting and the use of local flaps require hospitalization for surgery, and it may increase the financial burden.

In high-altitude, remote, and resource-limited areas, the timely and effective treatment of chronic wounds is an important clinical problem that requires an urgent solution. Therefore, this pilot study was conducted to evaluate the efficacy of granulation-embedded autologous skin grafting in patients with chronic wounds living in high-altitude areas in China.

Study design, setting, and participants

This study was approved by the Ethical Committee of the Yushu People's Hospital, and all subjects included in the study signed the informed consent form. Among patients with chronic wounds (average altitude 4493 meters) admitted to the Yushu People's Hospital from September 2021 to December 2022, a sample of 45 patients was retrospectively enrolled according to the following inclusion criteria: chronic wounds that had not healed or showed no signs of healing despite regular treatment for over 1 month; consent to undergoing surgery; and living in high altitudes. Patients with contraindications to surgical debridement, immunocompromised status, cancerous wounds, and unavailable follow-up data were excluded.

All enrolled patients received a preoperative evaluation, systemic treatment, and wound care according to a standard management protocol after admission. This included laboratory tests, imaging, anti-infection treatment, detumescence, and nutritional support. Patients were divided based on grafting approach used, into a stamp skin-grafting group (n = 22) and granulation-embedded skin-grafting group (n = 23).

Surgical grafting treatment

After the removal of necrotic tissue and edematous granulation tissue on the wounds by debridement, the wounds were treated by stamp skin grafting or granulation-embedded skin grafting.

For patients in the stamp skin-grafting group, stamp skin of 0.25-mm thickness was obtained from normal skin, and it was then affixed to pieces of gauze with petroleum jelly. The gauze pieces were further cut down to a size of approximately 25 mm² and then affixed to the wound.

For patients in the granulation-embedded skin-grafting group, stamp skin of 0.25-mm thickness was obtained from normal skin. The granulation flap on the wound was 8 × 8 mm and its thickness was 2 mm, which ensured that the granulation flap was evenly distributed on the wound. A 0.25-mm thick stamp skin sample was laid under the granulation flap to ensure that the dermal surface was in full contact with the base. The wound was covered with a sterile compression dressing. The details of a typical granulation-embedded skin grafting are shown in Figure 1, and the healing process is shown in Figure 2.

Outcome evaluation

The post-surgery survival rate of skin grafts, wound-coverage rate, and wound-healing time for each patient were recorded and the corresponding data were analyzed. The survival rates of the skin grafts on day 7 after surgery were assessed and calculated as (the skin graft survival area/total skin graft area) × 100%. The survival criteria for the grafts were that the skin graft was rosy in color, closely connected with the base, and presented with no exudation or secretion under the skin. The wound coverage rate on day 7 was assessed for both groups and was calculated as (original wound area - remaining wound area)/original wound area) × 100%. The wound-healing time was defined as the interval between the surgery and complete wound healing.

The length of hospital stay and 1% total body surface area (TBSA) treatment cost were evaluated to analyze the cost-effectiveness of the 2 skin-grafting approaches.

Baseline characteristics

The baseline characteristics of all enrolled patients are shown in Table 1. A total of 45 patients were enrolled with a mean age of 53.81 ± 3.84 years, including 24 males and 21 females, with mean wound sizes of 24.7 ± 2.9 cm² on lower limbs. There were no significant differences in the baseline demographic and clinical characteristics between the groups (all P > .05), as shown in Table 1.

Efficacy of granulation-embedded skin grafting

The skin graft survival rate in the granulation-embedded skin-grafting group was significantly higher than that in the stamp skin-grafting group (94% ± 3% vs 86% ± 3%, P < .01). Moreover, the wound coverage rate on postoperative day 7 in the granulation-embedded skin-grafting group was also significantly higher than that in the stamp skin-grafting group (61% ± 16% vs 54% ± 18%, P < .01). There was also a significant difference in the wound-healing time between the granulation-embedded skin-grafting group (23 ± 2.52 days) and the stamp skin-grafting group (31 ± 3.61 days) (P < .05), as shown in Figure 3. This indicated that the average healing time of granulation-embedded skin grafting was significantly less compared with stamp skin grafting.

Cost-effectiveness of granulation-embedded skin grafting

The length of hospital stay in the stamp skin-grafting group was significantly longer than that in the granulation-embedded skin-grafting group (28% ± 4% vs 19% ± 3.61%, P < .05). Moreover, the 1% TBSA treatment cost in the stamp skin-grafting group was also significantly higher than that in the granulation-embedded skin-grafting group (5791.67 ± 743.09 vs 3904 ± 792.69, P < .01), as shown in Figure 4.

It was found that the graft survival rate and wound coverage on day 7 after surgery were significantly better in the granulation-embedded skin-grafting group than in the stamp skin-grafting group. The wound healing time was also significantly shorter for granulation embedding than stamp grafting. At the same time, the length of hospital stay was shortened, and the cost of treatment was reduced.

Chronic wounds are caused by various factors, such as burns, diabetes, and venous ulcers. They are often associated with microcirculatory disorders and microvascular lesions.⁹ Venous ulcerations are caused by blocked blood reflux in the leg with excessive venous pressure in the vicinity.¹⁰ Blood reflux leads to blood stasis in the venous bed, resulting in long-term hypoxia and nutritional deficits in the local tissue.¹¹ Most chronic wounds associated with metabolic diseases involve vascular and nerve lesions that result in insufficiencies in local blood supply, paresthesia, ulcers, and possibly infections.¹² Also, chronic wounds formed by burns or trauma can occur due to local injuries that cannot be repaired in time, resulting in ischemia and hypoxia around the ulcer.¹³ In these cases, the wound cannot heal by itself due to the lack of oxygen and blood supply. Chronic wounds often contain complex biofilms. These biofilms form physical barriers that affect wound healing and extend the inflammatory phase of the wound, leading to repeated infection of the wound.¹⁴

In clinical practice, debridement involves the removal of foreign bodies, necrotic tissue, potential biofilm substances, and senescent cells from the wound.^15-17 This process transforms the chronic wound into an acute wound by re-establishing the molecular and cellular environment of the wound.¹⁸ When the condition of the wound is optimal, stamps, skin grafts, or flaps are used to cover the wound.

Granulation-embedded skin grafting is a method that can be used in the treatment of chronic ulcer wounds. In this study, the stamp skin was dissected using a scalpel and the edematous granulation tissue was removed. A granulation flap was made on the wound surface to form an acute wound. The presence of abundant capillaries in the deep layers of the granulation tissue can increase the blood supply to provide favorable conditions for the growth of skin.¹⁸ The granulation flap can cut off the fibrous tissue to prevent it from thickening, thus improving the hypoxic state of the wound. At the same time, the granulation flap also anchors the grafting skin, so it greatly reduces the possibility of the graft being accidentally dislodged during clinical care or dressing changes. Moreover, granulation-embedded skin implantation is feasible at the bedside, and local anesthesia avoids the risk of general or lumbar anesthesia.^19-20 In addition, it can shorten the course of the disease while reducing the patient's pain and financial burden.

In this study, the survival rates of the skin grafts on day 7 in the granulation-embedded skin-grafting group were significantly higher than those in the stamp skin-grafting group. This may be due to the conversion of chronic wounds into acute wounds and the blood supply provided by the basal layer. The granulation flap protects the grafting skin, significantly increasing its survival. Furthermore, the grafting skin becomes fused, so the wound coverage on day 7 was significantly higher. The wound healing time was also significantly shorter than that in the stamp skin-grafting group. Wound healing was accelerated, further reducing the length of hospital stay. Moreover, reducing the use of clinical consumables could lower hospital costs.

High-altitude areas are usually remote and economically depressed, with insufficient health resources.²¹ Residents in these regions often lack medical knowledge, resulting in a lower control rate of chronic wounds and higher possibility of chronic illness.²² As shown in this pilot study, granulation-embedded skin grafting for chronic wounds can help wound healing in these patients while shortening the hospital stay and reducing the economic burden. Granulation-embedded skin grafting provides a new option for chronic wound treatment at high altitudes, which is worth promoting.

There are some limitations in this study. First, despite being piloted at more than 1 site, the authors only reported on patients treated at 1 institution. A larger multicenter study will be required to validate these findings. Second, it was difficult to find patients with chronic wounds with similar characteristics and sizes in the established age range. Third, the follow-up period of the study was limited to 2 months.

It was found that the treatment of chronic wounds with granulation-embedded skin grafting resulted in a higher graft survival rate, shorter healing time, and lower hospitalization cost than stamp skin grafting. This approach could provide a new option for chronic wound treatment.

Acknowledgments: The authors appreciate all the staff of the burn and plastic surgery department for their efforts in treating patients and thank the patients' families for their care.

Authors: Cong-Mo Shen, MD¹; Yong-Zhang Qi, MD²

Affiliations: ¹Senior Department of Burns and Plastic Surgery, Fourth Medical Center of PLA General Hospital, Beijing, China; ²Department of Burns and Plastic Surgery, Qinghai University Affiliated Hospital, Qinghai, China

Disclosure: The authors disclose no financial or other conflicts of interest.

Correspondence: Yong-Zhang Qi, Qinghai University Affiliated Hospital, Xining 810016, Qinghai Province, China; qiyongzhangyx@163.com.

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