Allograft Adipose Matrix: A New Natural Approach with Evidence for 8-Year Longevity of Soft Tissue Augmentation

BACKGROUND

Soft tissue reconstruction, thus far, is limited to hyaluronic acid fillers or polymer-based biostimulation, which are artificial means for augmentation, and autologous fat transplant, which is more natural and has a high rate of reabsorption. Allograft adipose matrix (AAM; Renuva^®, MTF Biologics, Edison NJ), a new off-the-shelf option, is a decellularized human allograft tissue form with biophysical cues that allow for the patient’s own adipose tissue to repopulate the scaffold, resulting in volume restoration, as shown in this communication. Preclinical studies have shown that the AAM retains critical structural proteins reported to support fat formation¹. In addition, it is postulated that an adipose-derived architecture may support new blood vessel formation via infiltration of endothelial cells, creating a functional, three-dimensional scaffold (Figure 1).

Figure 1.

Schematic representation on the proposed mechanism of action for AAM and adipose tissue lifecycle. MSCs=mesenchymal stem cells. AAM= allograft adipose matrix. Created with BioRender.com.

Traditionally, the generation of adipocytes has been thought to be a dynamic process, responding to signals of growth, differentiation, apoptosis, and energy surplus. Adipose cells arise from a lineage of mesodermal multipotent stem cells from the vascular stroma, known as adipose mesenchymal stem cells (MSCs). MSCs undergo hyperplasia in response to growth signals (i.e., BMP4), which causes development to preadipocyte, and then further growth factors cause terminal differentiation to the mature adipocyte². The signaling factors leading to an adipogenic fate remain elusive. Mature adipocytes can only undergo hypertrophy, growing bigger due to lipogenesis. Mature adipocytes release factors that increase fat generation. Autologous fat transfers often fail, potentially due to low blood supply, leading to transplanted cell death. Mature adipocytes release paracrine signals for lipogenesis (i.e. leptin, adiponectin), and angiogenesis (i.e. VEGF, FGF-2, and TBF-β)³.

The organization and spatial configuration of adipose extracellular matrix provides specific environmental structural cues to support cell behavior through receptor-mediated interactions. The adipose tissue structure is rich in matrix proteins (collagen type V and VI, glycosaminoglycans), which are integral during adipocyte differentiation and the organization of fat lobules. Recent studies have demonstrated that the AAM structure supports host infiltration and new adipose tissue and blood vessel formation, which was assessed histologically^1,4, and resulted in volume restoration and retention in clinical studies.⁴

AAM has been tested in human subjects with minimal side effects. A multicenter study correcting atrophic temples found 75% volume increase from baseline with high patient satisfaction.⁴ However, the follow-up from this study is at 24 weeks. Herein, we describe a case study of a 53-year-old female with long-term outcomes post-AAM treatment at 8-years.

Patient Study

A 53-year-old female with a soft tissue defect in the right upper outer quadrant of the right buttock, secondary to steroid atrophy, was injected with AAM (Figure 2). Informed consent was obtained, and ethical guidelines of the 1975 Declaration of Helsinki were followed. The AAM tissue is aseptically processed without terminal irradiation from donated deceased human adipose tissue, which is recovered and screened in accordance with the American Association of Tissue Banks (AATB) and the U.S. Food and Drug Administration (FDA) regulations and guidelines. AAM meets ISO 10-993 biocompatibility testing panel and each donor must pass USP <71> Sterility Testing, and bacterial endotoxin screening using Limulus Amebocyte Lysate (LAL) requirements, before being released.

Figure 2.

Soft tissue defect due to steroid atrophy in right upper outer quadrant of right buttock before AAM procedure.

AAM was prepared following manufacturer instructions. No topical anesthetic, ice, or lidocaine was used. A 19-gauge cannula was threaded through 2 entry sites. At each entry site, 2.5 cc AAM was injected, totaling 5 cc of AAM into the defect. AAM was injected into the subcutaneous plane until the volume deficiencies were visually optimized. Any unused product was discarded.

Post-injection erythema and purpura were observed (Figure 3). The patient reported that this resolved in a few days. No other adverse events recorded. The patient was followed at 3-years, 5-years, and 8-years post treatment.

Figure 3.

Patient right buttock erythema and purpura immediately post-AAM procedure.

At the 8-year point, there is not an overt concavity or skin depression where the initial defect was located. Furthermore, skin tone, smoothness, texture, and overall appearance also improved (Figure 4). The patient reported satisfaction with the treatment progress overall.

Figure 4.

Patient right buttock 8-years after AAM procedure.

DISCUSSION

This communication demonstrates utilization of AAM in soft tissue augmentation in the subcutaneous plane with 8-year longevity. Prior studies demonstrate the adipogenesis and 6-month AAM retention^1,4. Overall, soft tissue augmentation and volume retention was evident over years with improved cosmesis.

Limitations include the patient-specific microenvironment with native fat prerequisite, as the adipogenesis is supported by the existing adipocytes. This may pose a concern in the current trend to utilize GLP-1 agonists. The side effects include infection, inflammation, bruising, and discoloration at injection site, which are minor in comparison to risks of general anesthesia in autologous fat transplant. These side effects are shared with hyaluronic acid fillers.⁵

CONCLUSION

AAM is a new solution for soft tissue volume restoration with potential to provide 8-year volume retention based on one case study. These findings require corroboration with large-scale case-control clinical trial. AAM can be used in facial and body augmentation, breast contouring, lipodystrophies, cleft lip and palate, and other genetic defects where a fat deficiency may be observed. This may be an attractive option for patients who prefer natural interventions that rely on the endogenous regenerative potential and is part of the expanding regenerative aesthetics portfolio.