Autologous fat grafting in the treatment of hard-to-heal wounds of lower extremities: surgical technique and examples

Introduction

Hard-to-heal wounds is a group of disorders, management of which is particularly challenging. They are defined as wounds not reduced by 40–50% after 4 weeks of standard of care (SoC) treatment including early intervention, accurate assessment of the wound, regular follow-up, optimal wound management strategy according to the TIME acronym (tissue debridement, infection and inflammation control, maintenance of moisture balance and proper environment for epithelization) [1].
Management of hard-to-heal wounds includes causal and local treatment, the latter containing debridement (surgical, enzymatic and biological) and application of various kinds of dressings [2]. Additional treatment includes negative pressure wound therapy (NPWT), hyperbaric oxygen therapy (HBOT), placement of split-thickness skin graft (STSG) or less often full-thickness skin graft (FTSG) [2]. A novel and promising approach for hard-to-heal wounds is autologous fat grafting (AFG) rich in adipose-derived stem cells (ADSCs) performed within the ulcer bed and edges in order to use regenerative and proangiogenic properties of ADSCs [3].

Objective

In this article we describe the surgical technique of AFG applied in management of hard-to-heal wounds of lower extremities and present six clinical cases of patients, who underwent AFG performed on ulcers particularly hard to treat in a standard way. We also discuss results observed during multi-month treatment duration.

Case reports

Surgical technique

AFG procedure consisted of the following steps:
1. infiltration of the anesthetic fluid into subcutaneous tissue at the site of lipoaspirate harvesting; 2. fat harvesting from the donor area; 3. lipoaspirate processing; and 4. fat application in the desired area.
The donor transplant site was a lower and lateral abdominal region. In these sites a surgeon made incisions, in which anesthetic fluid was administered (Step 1). For this purpose surgeons used various modifications of Klein solution.
The second step was conducted according to a standardized Coleman’s method [4, 5]. Through incisions mentioned above the lipoaspirate was harvested using 3-mm diameter, two-hole, blunt tip cannula connected to a Luer-Lock syringe. The volume of fat aspirate ranged from 10 to 100 ml depending on wound’s size and stage of healing.
In the third stage the removal of contaminants such as cell debris and oil droplets was achieved by gravity sedimentation, which resulted in separation into three distinct layers: top layer composed mainly of oil, middle layer being a fat tissue and the lower layer consisted of water, blood, lidocaine and fluid. The top layer was decanted and the lower layer was discarded by removing the plug from the syringe. The remaining middle layer was used as injection material.
In the fourth step the obtained material was injected into the wound’s bed and edges using 1.5-mm diameter cannula. Its volume ranged from 4 to 20 ml per wound.

Case reports and results

Six patients with hard-to-heal wounds of lower extremities previously treated according to Standard-of-Care underwent AFG one or several times giving results reported below.

Case 1

A 50-year-old patient with sarcoidosis, alcohol abuse and nicotine addiction suffered from three wounds located on the right leg: on the anterior surface, posterior surface and in the region of lateral malleolus. The patient had undergone debridement five times and STSG combined with NPWT. After a year of this procedure, the patient underwent his first AFG, which was then repeated two times. A size reduction of the remaining wound was observed and several months later all ulcers were totally healed (table 1, fig. 1).

Case 2

A 57-year-old woman, after a traffic accident in 1976, suffered from hard-to-heal wounds of the left lower leg and foot located in its lateral and medial region. Ulcers were treated with professional dressings as well as skin grafting with no significant improvement in healing. The patient had undergone AFG within above-mentioned wounds, which was repeated sixteen months later. During follow-up a healing improvement was observed (table 2, fig. 2).

Case 3

A 66-year-old woman with controlled type 2 diabetes and arterial hypertension suffered from a hard-to-heal wound located on the medial plantar region of the left foot in the course of the diabetic foot syndrome. The patient had undergone STSG, however a skin graft was lost after 2 months. AFG procedure was performed and healing improvement was reported in the next months (table 3, fig. 3).

Case 4

A 65-year-old man with arterial hypertension, recurrent venous insufficiency treated with two surgical interventions and a history of deep vein thrombosis, suffered from two hard-to-heal wounds located on the right lower limb: dorsal region of the foot and medial region of the lower leg. They were covered by STSG, which failed, remaining wounds that showed no tendency to heal by secondary intention. It was decided to perform AFG on the bed of each wound. After 2 years the progression of wound healing was observed (table 4, fig. 4).

Case 5

A 58-year-old man with obesity, arterial hypertension, atherosclerosis of lower extremities (for 5 years), alcohol abuse and nicotine addiction, suffered from hard-to-heal wounds located on the anteromedial region of the right lower leg. In the past the patient was treated with STSG and NPWT with no significant improvement in healing. He was also under supervision of vascular surgeons, however he did not qualified for revascularization procedure. It was decided to perform AFG. Nine months later the surgery was repeated due to poor healing outcomes. After that, the size of the ulcer was still unsatisfactory (table 5, fig. 5) and further follow-up was interrupted as the patient stopped visiting the outpatient clinic.

Case 6

A 58-year-old obese woman suffered from varicose veins of both lower extremities with an accompanying chronic ulcer located on the medial surface of the right leg. Venous insufficiency was treated two times with sclerotherapy and her hard-to-heal wound was treated with STSG, without success. Nine months later, the first AFG was performed. During this procedure a significant modification was introduced – autologous fat was not obtained by standard Coleman’s method, but it was excised from the subcutaneous tissue of hypogastrium. After several months AFG procedure was repeated with fat harvesting according to a standard Coleman’s method. At follow-up appointments a very fast healing improvement and wound size reduction in comparison to other cases was observed (table 6, fig. 6).

Discussion

Autologous fat grafting has a wide clinical application, especially in esthetic procedures like modelling of body parts e.g. breast, filling of wrinkles and lips, as well as in treatment of post-traumatic, iatrogenic and congenital deformities. A wide use of autologous fat results not only from being a biocompatible, safe and efficient filling material, but also from its regenerative properties [6]. Treatment of hard-to-heal wounds of various etiologies is another use of autologous fat’s potential. Publications suggest an accelerated wound healing after application of fat within its area [7–10]. Not only the ulcer size reduction was observed, but also pain reduction was reported [9, 10].
Additionally, autologous fat grafted into scars is associated with improvement of skin quality in a recipient site. AFG is also characterized by minimally invasive character of the procedure, as well as its simplicity and limited adverse reactions.
In five of six described cases the desired effect was achieved. Patients, in which a long-standing SoC, skin grafting and causative treatment did not bring prominent results, after AFG procedure had a size reduction or closure of a wound without recurrences observed during the follow-up.
Satisfactory outcomes of AFG in wound healing are attributed to the presence of ADSCs in fat tissue, which are the pluripotent stem cells [11]. They are a part of subpopulation of cells isolated from adipose tissue and separated from adipocytes called stromal vascular fraction (SVF) [11]. ADSCs present self-renewing capacity and can differentiate into keratinocytes and fibroblasts playing a crucial role in wound regeneration and remodeling, as well as extracellular matrix component production. These cells also release different growth factors with proangiogenic properties such as hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), different cytokines and chemokines, growth factors and chemokines, which stimulate angiogenesis and damaged tissue regeneration [3]. Their ability to differentiate into endothelial cells along with proangiogenic factor production may contribute to formation of new vessels [12]. Development of the vascular network enables formation of granulation tissue. Also fibroblasts and macrophages recruitment is promoted by ADSCs [13]. Nevertheless, the exact role of fat tissue in wound healing promotion is still not fully understood.
In case 5, AFG did not bring the expected results. Advanced atherosclerosis disqualifying the patient from revascularization procedure, resulted in inadequate blood supply to the wound area, which may have affected the healing process. Additionally, nicotinism may have contributed to this situation, as well as alcohol abuse and poor patient compliance in terms of appropriate wound care and taking care of total wellbeing. Case 5 confirms that despite previously described good results of AFG in majority of patients there are of course instances of treatment failure [9]. The indications and contraindications for wound treatment with fat grafting need future research.
The above-described technique is one of several methods of autologous fat grafting used in treatment of hard-to-heal wounds. In the literature there are many modifications described aimed to improve the effectiveness of this procedure in healing of wounds and reduce the volume of material injected into the ulcer area. One of them is cell-assisted lipotransfer (CAL), in which either SVF extracted from a separate sample of lipoaspirate or purified ADSCs are added to processed lipoaspirate before injection [14]. Another way is to administer purified or culture-expanded ADSCs alone, as well as administer purified SVF alone [15].
In case 6, during the first AFG, the modification was introduced, namely a fat tissue was harvested from the excised subcutaneous tissue followed by mechanical fragmentation, dilution in Klein solution and sedimentation. The effect of this AFG was noticeable – wound dimensions decreased by 1 cm in length and width after 2 months of follow-up. Although such procedure can result in a larger scar in the donor area, the outcome of wound healing was satisfactory. Because of the limited number of reports of wound treatment with the use of autologous fat harvested in this manner, future research can explore this method.

Conclusions

In 5 of 6 presented cases, autologous fat grafting improved healing of chronic wounds located on lower extremities. The described technique proved to be effective, fast in performance and with a limited number of adverse effects. Presented cases support previous reports that AFG may promote healing [14] and suggest that the described technique may be a therapeutic option for this condition, however there are instances of treatment failure. In order to take full advantage of autologous fat’s potential, standardization of the surgical technique that provides the greatest improvement in healing depending on the ulcer size and etiology is needed. In order to better understand how the presented procedure affects the mechanism of wound healing, further research on ADSCs and their regenerative potential is required.

Funding

No external funding.

Ethical approval

Not applicable.

Conflict of interest

The authors declare no conflict of interest.

References