Proficiency of Topical Platelet-Rich Plasma Over Vacuum-Assisted Closure for Chronic Wound Healing: A Clinical Prospective Comparative Study

INTRODUCTION

Chronic wounds are common conditions that greatly impact patients’ quality of life.^[1] These wounds are chronic wounds that do not heal or require a long time to heal and often recur and are becoming more frequent due to population ageing and increasing comorbidities.^[2] They place a heavy burden on the healthcare system due to the high cost of dressing materials, amputation-related costs, and the prolonged, continuous need for human resources for wound management.^[3] The healing of chronic wounds is a topic of scientific inquiry. Despite the emergence of sophisticated therapeutic approaches, a certain proportion of chronic wounds still fails to heal completely.^[4]

The process of wound healing is a physiological phenomenon that involves a series of intricate events, beginning after the skin has been damaged and culminating in the successful restoration of its integrity and functionality. This process involves four sequential and overlapping phases: haemostasis/coagulation, inflammation, proliferation, and remodelling. However, several pathological conditions can disrupt this efficient and well-regulated process, resulting in delayed wound healing or failure, which can lead to chronic wounds. The factors contributing to chronic wounds include local elements (infection, continuing inflammation, and necrotic tissue) and additional clinical or social conditions (ageing, frailty, inadequate blood flow, obesity, vascular diseases, diabetes, malnutrition, severe burns, excessive pressure, immunosuppression, or malignancy). Chronic wound causes are highly diverse, but one crucial element in selecting the appropriate treatment is the origin of the wound, known as aetiology, which includes wounds caused by venous, diabetic, pressure, and arterial ulcers.^[4]

Besides treating the underlying cause, the goal of wound management is to promote healing through professional wound care; the gold standard methods are advanced dressings and compression therapy.^[5] Vacuum-assisted closure (VAC) therapy has been used to treat complex wounds. It is a dynamic and non-invasive system based on the application of air suction at a controlled sub-atmospheric pressure. It facilitates healing by improving the rate of angiogenesis, endothelial proliferation, the integrity of the capillary basement membrane, capillary blood flow and capillary calibre, as well as decreasing interstitial oedema and bacterial burden within the wound.^[6] The reason for the extensive approval of the VAC method by therapists and its widespread application is due to the remarkable clinical outcomes it delivers.^[7]

Several studies have reported the successful use of platelet-rich plasma (PRP) in chronic wounds, including diabetic foot ulcers, venous leg ulcers, pressure ulcers, and surgical wounds.^[8] PRP is a novel therapy that has recently gained interest as a potential treatment option for chronic wounds. The mechanism of PRP action in chronic wounds involves the release of growth factors and cytokines, which promote the migration and proliferation of cells engaged in wound healing, such as fibroblasts and endothelial cells.^[9,10] Activated PRP (aPRP) with a concentration four times the normal amount of platelets (1,000,000 platelets/µl) is a cost-effective and easily accessible blood derivative that has the ability to promote cell growth and maturation. Activated platelets stimulate the upregulation of cellular mitogenesis and angiogenesis.^[9] The high concentration of leukocytes and its autologous nature contribute to its ability to perform local debridement and exhibit antibacterial activity without inducing an immune response.^[10] Autologous aPRP is not only effective in promoting wound healing, but it also aids in the regeneration of skin tissue.^[11] It is significantly beneficial in promoting the healing of fracture wounds, and it serves as a treatment for skin defects or dental mucosal injuries.^[12] In chronic wound management, PRP has shown promising results. Despite the promising results of PRP in chronic wound management, more robust clinical trials are needed to establish its efficacy and safety. Although many studies have evaluated both techniques individually, very few have compared them. Therefore, we conducted a prospective clinical comparative study to evaluate the proficiency of topical PRP over VAC in the management of chronic wounds.

MATERIAL AND METHODS

This prospective randomised comparative study included 102 patients who presented with chronic wounds at the Karnataka Institute of Medical Sciences, Hubli, Karnataka, from August 2022 to August 2023. Adult patients aged 18–70 years with a history of chronic wounds of various aetiologies that have not healed for 3 weeks or more with an inflammatory origin, despite the treatment of the underlying causes and appropriate local wound management, and who were treated with autologous PRP under compassionate use and wound area without the exposure of bone, muscle, ligaments, or tendons were included. Patients with chronic renal or hepatic impairment, sinuses of unknown depth or origin, wounds with malignancy, unstable fractures, untreated osteomyelitis, wounds with open joints, wounds with exposed blood vessels or organs, thrombocytopenia, haemodynamic instability, systemic use of corticosteroids, and pregnant women were excluded from the study.

Patients who satisfied the inclusion criteria were informed about the entire treatment and follow-up process, their consent was obtained voluntarily before they were treated with PRP, and their follow-up information was recorded. The study was carried out in accordance with the guidelines set out in the Declaration of Helsinki while simultaneously ensuring the privacy and well-being of the patients.

RESULTS

This study included 102 patients: 50 in the PRP group and 52 in the VAC group. The age of the patients ranged from 18 to 70 years, with a mean age of the patients in the PRP group of 34.9 and 38.8 years in the PRP and VAC groups, respectively. In the PRP group, 78% (n = 39) of the patients were males and 22% (n = 11) were females in the PRP group. In the VAC group, 73.07% (n = 38) were male and 26.92% (n = 14) were female in the VAC group, showing male predominance in both the PRP and VAC groups.

The aetiologies of the two groups did not differ. Posttraumatic wounds were the most common type of wound, accounting for 66% (n = 33) of PRP and 55.7% (n = 29) in the VAC group, followed by venous ulcers, neuropathic ulcers, postsurgical wounds, and postburn wounds. Diabetes was the most common comorbidity, present in 66% (n = 33) of the PRP group and 71.15% (n = 37) of the VAC group, followed by hypertension in 20% (n = 10) of the patients in the PRP group and 21.15% (n = 11) in the VAC group. With respect to the assessment of health status, no notable differences were observed between the two groups in terms of American society of anesthesiologists (ASA) classification and frequency of comorbidities.

Most patients in the PRP and VAC groups had moderate pain in 60% (n = 30) of the PRP group and 69.23% (n = 36) of the VAC group, followed by mild pain in 34% (n = 17) of the PRP group and 21.15% (n = 11) in the VAC group; 6% (n = 3) in the PRP group and 9.61% (n = 5) of the VAC group had severe pain. Noticeable pain was observed using pain assessment scores in the VAC group compared with the PRP group throughout the duration of the study. Only 38% (n = 9) of the patients in the PRP group required split-thickness skin grafting, and approximately 75% (n = 39) of the patients in the VAC group required split-thickness skin grafting. Secondary healing was observed in 62% (n = 31) of the patients in the PRP group and in 25% (n = 13) of the patients in the VAC group.

The characteristics of the patients included in this study are presented in Table 1 and Figures 1–6. The duration of complete wound healing was lesser (3–8 weeks) in the PRP group than that in the VAC group (3–12 weeks) [Figure 7].

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Figure 1:

Frequencies of male and female patients present in the study groups. PRP: Platelet rich plasma, VAC: Vacuum assisted closure.

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Figure 2:

Mean age of the patients in the study groups. PRP: Platelet rich plasma,VAC: Vacuum assisted closure.

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Figure 3:

Frequencies of comorbidities present in patients in the study groups. PRP: Platelet rich plasma, VAC: Vacuum assisted closure, DM: Diabetes mellitus, HTN: Hypertension.

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Figure 4:

Frequencies of the types of wound present in the study groups. PRP: Platelet rich plasma, VAC: Vacuum assisted closure.

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Figure 5:

Frequencies of pain scores observed in patients in the study groups. PRP: Platelet rich plasma, VAC: Vacuum assisted closure.

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Figure 6:

Frequencies of secondary healing and split-thickness skin grafting used for wound closure in patients in the study groups. PRP: Platelet rich plasma, VAC: Vacuum assisted closure.

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Figure 7:

(a) Post-operative wound on the right foot pre-VAC application. (b) Post-application of VAC after four sessions, wound well granulated. (c) Split-thickness skin graft application. (d) Well-taken skin graft 100% graft uptake. (e) Post-debridement wound over the right heel. (f) PRP session-1. (g) PRP session-5. (h) PRP session-6 and (i) Complete healing of the wound in the right heel after PRP treatment.

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DISCUSSION

Chronic non-healing wounds represent a major healthcare burden and pose a significant challenge to patients and healthcare providers. There is growing interest in the application of PRP as a potential therapeutic modality for non-healing wounds and ulcers. In this study, we evaluated the efficacy of PRP injections over VAC application for the treatment of chronic wounds. Our study found that autologous platelet application led to significant reductions in wound size in all treated patients, with wound healing observed as early as 3 weeks after post-PRP treatment. These findings are consistent with those of several previous studies that reported the effectiveness of PRP in the treatment of chronic non-healing wounds and ulcers. For instance, a randomised controlled trial by Frykberg et al. found that PRP treatment led to significant improvements in wound healing rates and wound size reduction in patients with diabetic foot ulcers compared to the control group.^[15] Similarly, a systematic review and meta-analysis by Xiong et al. reported that PRP treatment led to a significant reduction in ulcer size and improved wound healing rates in patients with venous leg ulcers.^[16] In addition, our study found no bleeding, infection, or procedure-related complications, which is consistent with the findings of several previous studies that have reported the safety of PRP treatment for chronic non-healing wounds/ulcers.^[8,15,17]

In a study conducted by Arora et al., the development of granulation tissue was observed on the 9th day following the application of PRP alone.^[18] On the 23rd day, complete granulation tissue formation was noted, accompanied by a 1.6% reduction in wound size. Complete wound coverage was achieved on the 25th day. In comparison, when PRP was used in conjunction with VAC dressing, granulation tissue appeared on the 4th day. Complete granulation tissue formation was observed on the 13th day, and total wound coverage was achieved in 15 days. This resulted in a 14-day reduction in hospital stay and a notable decrease in wound size by 3.9%.^[18]

VAC treatment has been introduced as a component of the therapy for patients with chronic wounds. These devices operate by maintaining a moist environment, optimising blood flow, removing exudates, and applying negative pressure to promote wound closure. It can initiate numerous factors that may be absent in chronic wounds. Additionally, numerous studies had demonstrated an increased rate of granulation tissue formation with this devices.^[19] The present study differed from previous trials in the type of comparison. In this study, we compared the effects of PRP and VAC on chronic wound healing.

Armstrong and Lavery found that most wounds healed by secondary intention after VAC application in 40% of 77 patients without definitive surgical interference. Less than 16% of patients in the VAC group had healed wounds after undergoing surgical closure.^[20] On the contrary, in this study, split-thickness skin grafts were more commonly used for wound coverage in both groups, especially in the VAC group (39, 75%) than in the PRP group (19, 38%). Patients who received PRP treatment showed complete healing as early as 3–8 weeks compared to those in the VAC group, which healed completely at 3–12 weeks. More pain was noticed in most patients in the VAC group compared to the PRP group. The differences in mild, moderate, or severe pain may be due to the unique characteristics of each wound, such as the size, site, cause, or type of tissue affected.

Kakudo et al. used autologous PRP in the management of five patients with non-healed wounds and found that there was complete healing within 4 weeks in three wounds, with an average of 6.6 weeks in epithelialisation of wounds.^[21] Suthar et al. described that there was decrease in size of the wound, and the mean time of wound healing was 8.2 ± 1.9 weeks in 24 patients with one non-healed wound in every patient using a single dose of a combination of autologous PRP gel and PRP injections administered subcutaneously around the wound periphery, and all the patients showed significant wound healing.^[22] Horn et al. reported that an aPRP gel effectively decreased the width and depth of chronic wounds. The present study confirms their findings.^[23] In our study, the time to complete wound healing in the PRP group was 3–8 weeks, which is similar to the findings of Suthar et al. Hence, most researchers have used PRP effectively to treat non-healing chronic wounds.^[22]

Autologous aPRP provides an economical and affordable solution because it is prepared using a small amount of the patient’s blood; only 7 cc is obtained from 30 cc of freshly drawn venous blood. This eliminates the concern of transmitting blood-borne diseases or experiencing an immunological reaction. Autologous aPRP offers the necessary growth factor for the natural healing process in patients with diabetes.^[24] Seven protein growth factors, which are actively secreted by platelets, play a critical role in initiating the wound healing process. aPRP contains three proteins that serve as cell adhesion molecules, which are fibrin, fibronectin, and vitronectin.^[25] Platelets play a crucial role in the healing process of wounds by secreting transforming growth factor-beta (TGF-β) and monocyte chemoattractant protein-1, which attracts monocytes and neutrophils to the site of injury. By utilising PRP, the risk of amputation can be significantly reduced, as it accelerates the healing of chronic wounds.^[26]

Our study has several limitations. First, the sample size was small, which limits the generalisability of the findings. Second, the absence of a control group renders it challenging to determine the extent to which the observed improvements in wound healing can be attributed to the PRP and VAC treatments. At the same time, there was a lack of control over some confounding factors, including patients’ activities, intake of nutrition, and level of adherence to medical treatments, which are some of the limitations of the present study.

CONCLUSION

Our study suggests that PRP dressings are more effective than VAC dressings in treating chronic non-healing wounds. PRP has demonstrated its superiority over Negative pressure wound therapy (NPWT) owing to its simplicity, safety, cost-effectiveness, shorter procedure time, reduced pain, absence of hospitalisation, and autologous nature in the preparation. However, further studies with larger sample sizes, control groups, and longer follow-up periods are needed to confirm these findings and determine the optimal PRP treatment protocol for chronic non-healing wounds.