Injectable Allograft Adipose Matrices in the Management of Chronic and Postoperative Wounds: A Retrospective Analysis

Chronic wounds are those that do not progress through the healing process in a timely manner. They are a significant challenge to patients and health care systems, with an estimated 2.4 million to 4.5 million people currently affected in the United States alone.¹ Chronic wounds are often managed as a comorbidity of other conditions, such as diabetes and peripheral vascular disease.² Because of the significant humanistic and economic burden at both an individual level (eg, quality of life) and a societal level (eg, health care costs), it is crucial to find effective treatments for patients with chronic wounds.³ Currently, there is a lack of clinical options for the management of chronic wounds or ulcers when debridement, skin grafting, or negative pressure wound therapy dressings are unsuccessful. This frequently leads to limb loss or amputation.⁴

One technique for wound treatment or atrophy prevention that has been successfully implemented in all anatomic regions is autologous fat grafting. This type of grafting has a variety of clinical indications, including soft-tissue defects, contour irregularities, and volume augmentation.^5,6 However, it has only recently been applied to chronic wounds or ulcers following unsuccessful conservative management techniques such as wound dressings or debridement^6,7; thus, additional research is needed to confirm its viability in chronic wound restoration. Use of decellularized adipose matrix to fill soft tissue defects has been extensively studied for its potential to replace intensive and complex stem cell injections. AAM is the extracellular component of adipose tissue, sans lipid and cellular components, that encourages local ECM growth for healing.⁶ AAM provides an ECM that functions as a scaffold for patients to create new fat. This is owing to preservation of naturally derived endogenous components such as matrix proteins, cytokines, and growth factors that are robust supporters of angiogenesis and adipogenesis. Specifically, factors within AAM such as adiponectin, leptin, angiopoietin, insulin-like growth factor 1, fibroblast growth factor 1 and 2, PDGF-BB, and VEGF have been noted to promote cell survival. Previous evidence in animal models has shown that human fat grafting can lead to neovascularization, increased synthesis of type I collagen, and increased dermal thickness via fibroblast recruitment.⁸ Moreover, clinical results in radiation-induced lesions indicate that AAM application led to enhanced tissue regeneration, neovasculature formation, and symptomatic relief.⁹

Clinical use of AAM in chronic wounds has also been encouraging but lacks compelling scientific evidence. In addition to its primary role of promoting wound healing, AAM is a ready-to-use, off-the-shelf preparation, which reduces the cost, time, and pain of adipose tissue collection. Given the lack of adequate literature either in favor of or against the use of AAM in the management of chronic wounds, the authors of the current study sought to understand the short-term efficacy and complications of AAM application on chronic wounds. This case series describes the effectiveness of AAM in the management of chronic wounds in 11 patients.

This retrospective case series uses collected data on patients with chronic wounds undergoing AAM treatment. Patients who presented with 1 or more chronic nonhealing wound of any etiology, location, and length of chronicity were recruited for the study. Exclusion criteria included patients with multiple chronic wounds or those who had undergone skin grafting for wound repair. Patients were then treated with Leneva AAM (MTF Biologics) injections, which is a human adipose tissue functioning as an ECM for tissue reconstruction. This matrix functions as a scaffold for the patient’s own cells to create new fat and allow for wound healing. Current clinical applications include pressure-related wounds, tunneling wounds, diabetic foot ulcers, and fat pad reconstruction procedures, among others.

All wounds were initially debrided with a curette to remove any fibrin, biofilm, or additional debris. This was followed by adequate irrigation. The AAM was applied using a 1.5-mL syringe. The matrix used was of a paste-like consistency rather than a very liquid material. The matrix was then applied to the wounds, covered with a foam dressing, and reapplied as needed. The number of follow-up appointments were determined by the PI (R.D.G.), and wound dimensions were recorded and photographs were taken during each visit. The AAM was reapplied according to the PI’s clinical judgment at follow-up visits. Data variables recorded for each wound included location, etiology, chronicity, number of AAM applications, and duration of follow-up. In addition, the patients were evaluated for possible complications related to wound healing and infection. The study was deemed exempt by the Northwestern University institutional review board.

Eleven patients (7 males, 4 females), each with 1 chronic wound, were recruited for this case series. The average patient age was 65 years (range, 35–79 years). One patient had diabetes. Table 1 provides a summary of patient demographics and wound characteristics. The wound etiologies were postoperative (n = 7), traumatic (n = 2), and foot ulcer (n = 2). In terms of wound location, there were 2 wounds on the head, 3 on the right lower extremity, 5 on the left lower extremity, and 1 on the abdomen. Average wound dimensions measured 8.45 mm × 7.36 mm, and the average chronicity was 3.77 months. Ten patients received only 1 application of the AAM, and 1 patient received 2 treatments 5 days apart. The average follow-up time after AAM application was 6.6 weeks. Seven patients (63%) achieved wound closure. Of these 7 wounds, 4 (57%) healed within 1 week of application, and the other 3 achieved closure at 4 weeks, 2 months, and 3 months, respectively. Four patients experienced incomplete wound healing, that is, adequate closure was not achieved. All 4 of these patients underwent primary suture closure at either 1 week, 2 weeks, or 3 weeks after AAM treatment.

Table 2 shows the number of applications and wound outcomes. The longitudinal outcomes after administration of AAM are shown in Figure 1 and Figure 2. Both hard-to-heal chronic wounds are examples of foot ulcers that required one usage of AAM. Wound dimensions were monitored at frequent visits to illustrate the filling efficacy of the matrix and progression of healing.

Previous literature has illustrated the clinical benefits of AAM, particularly in the diabetic foot, but there remains a need for additional studies on the application and effectiveness of AAM.^10,11 The current case series demonstrated wound closure in majority of patients (63%). Notably, 4 (57%) of these 7 closed wounds were healed within 1 week after AAM application. In 2017, Shahin et al¹⁰ advocated for the use of AAM in chronic wounds, highlighting its ability to reduce tissue stress over preulcerative and postulcerative lesions. They noted that this effect improved time to wound healing.¹⁰ In the current case series, most wounds had substantial depth and chronicity, and the use of AAM resulted in faster epithelialization compared with standard packing or dressing changes, as illustrated in the literature.^10,11

Soft tissue loss is commonly associated with traumatic injury, chronic disease, advanced age, or surgery. Often these wounds can be repaired by adipose tissue grafting when the size of the defect is not large enough to require flaps or implants.¹² Stasch et al⁴ further emphasized the role of fat grafting in promoting wound healing as well as mitigating pain. Importantly, in the current case series the use of an AAM provided an ECM that functions as a scaffold for patients to create new fat. Specifically, factors within AAM such as adiponectin, leptin, angiopoietin, insulin-like growth factor 1, fibroblast growth factor 1 and 2, PDGF-BB, and VEGF have been noted to promote cell survival. These factors also play a key role in endothelial cell growth and glucose and lipid metabolism, both of which can further augment wound healing.¹⁰ Given the decellularized structure of AAM, the tissue also retains the native structural and biochemical characteristics that allow for sufficient growth and granulation tissue formation.¹³ Zuk et al¹⁴ described this characteristic of processed lipoaspirate and its distinction from MSCs. This is relevant because the clinical use of MSCs in other treatment modalities has presented problems for patients, including additional pain, morbidity, and a low cell count upon harvest, all of which ultimately diminish the wound healing effect.

This case series has limitations. First, the number of follow-up visits and time to follow-up were inconsistent among patients. The follow-up was at the discretion of the PI (R.D.G.) who provided treatment for all patients included in this series. Reapplication of AAM, which was necessary for 1 patient, was also determined on the clinical judgment of the PI rather than a standardized clinical protocol. Second, this small series is meant to be hypothesis generating rather than a concluding study with level I evidence. There was no control group, and all 11 patients were administered AAM to highlight the potential benefit of this matrix in difficult-to-heal wounds. Patients in this series had a variety of wound locations and chronicity. Only 1 patient had a history of diabetes, but additional comorbidities (eg, hypertension, peripheral vascular disease) may confound results.

Future studies that include a larger sample of specific chronic wounds and a more regulated AAM treatment protocol would assist in evaluating the effectiveness of AAM in wound healing and its clinical course. This will be important for determining the specific indications for the clinical use of AAM. Additionally, the use of AAM with negative pressure wound therapy or additional matrices should be studied.

Injectable AAM is marketed as a viable, easy, and ready-to-use treatment option for chronic wounds of various etiologies. AAM shows promising results for enhancing wound healing by providing a scaffolding for cell growth and promoting sufficient granulation tissue formation. The initial data reported herein support the ability of AAM to improve chronic wound regeneration. This study is intended to be hypothesis generating, and clinical trials are needed to further substantiate the efficacy of AAM in chronic wound healing.