Advances being made in engineering of injectable soft tissue filler
Fillers have become a mainstay in cosmetic and rejuvenation treatments in aesthetic medicine today. A recent study demonstrates that a novel tissue-engineered filler, developed using a combination of adipose stem cells (ASC) and micronized acellular dermal matrix (Alloderm), is showing promise for many cosmetic and medical indications. Its developers claim it offers a softer, more natural appearance and may raise the bar in terms of aesthetic outcomes in procedures utilizing dermal fillers.
Various filling methods such as fat injection and grafts, as well as popular collagen and hyaluronic acid fillers, are used for cosmetic and medical indications for the treatment of rhytids, loss of subcutaneous tissue secondary to congenital malformation, trauma and extirpation. However, many of these approaches have several limitations including donor-site morbidity and deformity, unsatisfactory and unpredictable results and may have related issues of potential allergy associated with complications and subsequent toxicity to the filler.
OPTIMIZING INJECTABLES
“In using this unique approach with ASCs and micronized Alloderm, we hoped to circumvent many of the common problems encountered with other filler approaches used in plastic surgery,” Jin Soo Lim, M.D., of the Department of Plastic Surgery at The Catholic University of Korea, Seoul, Korea, tells Cosmetic Surgery Times . “It appears that ASCs are an ideal autologous cell source for adipose tissue engineering, and its combination with Alloderm can result in a softer, more natural injectable soft tissue filler.”
Dr. Lim and his team aimed to develop a unique soft tissue filler using the combined strengths of adipose tissue equivalents (which were constructed using ASCs) and micronized Alloderm. In the study, cultured human ASCs were first labeled with fluorescent green protein (to determine whether adipose formation in complexes originated from seeded cells or from surrounding perivascular tissue) and then attached to micronized Alloderm (5×105 cells/1mg). These ASC-Alloderm complexes were subsequently cultured in adipogenic differentiation media for two weeks, and then injected subcutaneously into the dorsal cranial region of nude male mice. Of the eight mice used in the study, four control mice were injected only with micronized Alloderm, and four were injected with ASC-Alloderm complex. The viabilities of the ASCs in micronized Alloderm were determined at 1, 4, 7 and 14 days, and the complexes, which had been cultured for 14 days and implanted in vivo for two months, were histologically evaluated by light, confocal and scanning electron microscopy (SEM).
Results showed that the ASCs in the micronized Alloderm were alive during all time points in the culture period. Light microscopy and SEM evaluations showed that the ASC-Alloderm complexes cultured for 14 days contained round cells with large lipid vesicles and many spherical cells thought to be adipocytes, respectively. Histologic evaluation showed that the ASCs in implanted ASC-Alloderm complexes, which were harvested from mice at two months post-injection, differentiated into adipocytes which had the green fluorescent dye. The H&E evaluation in the control mice which had only received micronized Alloderm showed that some fibroblast-like cells and small capillaries had infiltrated the micronized dermal matrix, whereas in the mice that had received ASC-Alloderm complexes, markedly increased numbers of large signet-ring cells and large capillaries were observed.
“Micronized Alloderm can potentially be a useful medium in which human ASCs can grow and differentiate and serves as a good scaffold for human ASCs when constructing fat tissue for filling and plastic reconstruction purposes,” Dr. Lim says. “This newly grown fat tissue can be used in many medical and cosmetic three-dimensional soft tissue filling scenarios and may ultimately prove to be more advantageous than other currently available filler procedures and modalities.”
ALL IN THE MIX
Alloderm can be injected alone as a filler but in order to achieve long-lasting cosmetic results, cell in-growth and revascularization of the micronized Alloderm is necessary — but according to Dr. Lim, this does not occur in all patients. Sufficient amounts of ASCs have the ability of high proliferation and a strong differentiation to adipocytes and endothelial cells, and mixing the Alloderm with ASCs can potentially improve the aesthetic results of this tissue-engineered filler. Dr. Lim says that, due to the natural approach of this novel soft tissue filler, common unwanted adverse events as sometimes seen with other filling modalities can be avoided.
“The differentiated adipocytes from the ASCs mixed in the micronized Alloderm medium make the injected micronized Alloderm a more acceptable soft tissue substitute, and the differentiated endothelial cells enhance the implantation of the injected soft tissue constructs,” Dr. Lim adds.
SELECTION IS KEY
The choice of stem cells and scaffolding used in tissue engineering plays a central role in the degree of success of adipose tissue engineering. According to Dr. Lim, injectable scaffolds can widen the scope of engineered adipose tissue and Alloderm used on its own has been successfully implemented in soft tissue augmentation for the treatment of wrinkles and scars.
Its developers allow that the ASC-Alloderm complex approach is a more complex and time-consuming procedure than using off-the-shelf dermal fillers. Nevertheless, they say, it can result in a viable injectable soft tissue filler with enduring aesthetic benefits.
REFERENCE
Yoo G, Lim JS. Tissue engineering of injectable soft tissue filler: using adipose stem cells and micronized acellular dermal matrix. J Korean Med Sci. 2009;24:104-109. Epub 2009 Feb 28.
Publish date: Jun 1, 2009 Modern Medicine
