A multi-center, open-label, pilot study of allograft adipose matrix for the correction of atrophic temples.

BACKGROUND: Autologous fat grafting (AFG) and synthetic fillers are currently used in esthetic and reconstructive surgery. Challenges in AFG include inconsistent graft retention, donor site morbidities, insufficient harvest, and excessive harvesting times. An allograft adipose matrix (AAM) has been developed as an off-the-shelf alternative to AFG and synthetic fillers. AIMS: To evaluate the clinical safety and retention of an AAM over 24 weeks after treatment of bilateral atrophic temples. PATIENTS/METHODS: Ten subjects (nine females, one male, aged 47-69 years) with temple atrophy were enrolled in the IRB-approved study. AAM (Renuva® , MTF Biologics, Edison, NJ) was injected (<3 mL) bilaterally into the atrophic temples of each subject. Volume retention, global improvement, and safety were evaluated at 1, 4, 8, 12, 16, 20, and 24 weeks. Biopsy specimens were obtained for adipogenic and angiogenic histological evaluation. RESULTS: The mean temple volume improved over the baseline and was retained throughout the study period. Fullness (measure of volume) increased immediately from 0 pretreatment to 2.8 post-treatment (scale 0-4 = none-maximum). Fullness varied from 0.8 to 2.2 from weeks 1 through 12 and was 2.7-3.0 from weeks 16-24, around 75% increase from baseline. Furthermore, skin tone, smoothness, texture, and overall appearance also improved with 71% of subjects being satisfied to very satisfied with the results. Adverse events were minimal and histology revealed native tissue incorporation and remodeling. CONCLUSION: AAM is safe and well tolerated, provides at least 6-month volume retention, improves skin quality, and supports adipose tissue remodeling after treatment into temples.

Clinical Evaluation of an Off-the-Shelf Allogeneic Adipose Matrix for Soft Tissue Reconstruction.

Biomaterials derived from human adipose extracellular matrix have shown promise in vitro and in animal studies as an off-the-shelf adipogenic matrix for sustained volume replacement. Herein, we report the results of a randomized prospective study conducted with allograft adipose matrix (AAM) grafted into the pannus of presurgical abdominoplasty patients 3 or 6 months before scheduled surgery. This is the first report of a longitudinal histologic analysis of AAM in clinical use. METHODS: Ten healthy patients undergoing elective abdominoplasty were recruited to receive AAM before surgery. Enrolled subjects were randomized into either a 3-month follow-up cohort or a 6-month follow-up cohort. Subjects were monitored for adverse events associated with AAM grafting in addition to undergoing serial biopsy. Following surgical excision of the pannus, representative samples from the AAM surgical sites were stained and evaluated with hematoxylin and eosin for tissue morphology, Masson's trichrome for collagen, and perilipin for adipocytes. RESULTS: All subjects tolerated AAM with no severe adverse events reported. At 3 months following implantation, AAM remained visible within the confines of the subjects' native surrounding adipose tissue with sparse adipocytes apparent within the matrix. By 6 months, AAM had remodeled and was primarily composed of perilipin-positive adipocytes. Histologic analysis confirmed tissue remodeling (hematoxylin and eosin), adipogenesis (perilipin), and angiogenesis (Masson's trichrome) occurred with the presence of AAM. CONCLUSIONS: AAM is a safe, allogeneic, off-the-shelf regenerative matrix that is adipogenic and noninflammatory and promotes angiogenesis.

Injectable Allograft Adipose Matrix Supports Adipogenic Tissue Remodeling in the Nude Mouse and Human.

BACKGROUND: Adipose tissue reaches cellular stasis after puberty, leaving adipocytes unable to significantly expand or renew under normal physiologic conditions. This is problematic in progressive lipodystrophies, in instances of scarring, and in soft-tissue damage resulting from lumpectomy and traumatic deformities, because adipose tissue will not self-renew once damaged. This yields significant clinical necessity for an off-the-shelf de novo soft-tissue replacement mechanism. METHODS: A process comprising separate steps of removing lipid and cellular materials from adipose tissue has been developed, creating an ambient temperature-stable allograft adipose matrix. Growth factors and matrix proteins relevant to angiogenesis and adipogenesis were identified by enzyme-linked immunosorbent assay and immunohistochemistry, and subcutaneous soft-tissue integration of the allograft adipose matrix was investigated in vivo in both the athymic mouse and the dorsum of the human wrist. RESULTS: Allograft adipose matrix maintained structural components and endogenous growth factors. In vitro, adipose-derived stem cells cultured on allograft adipose matrix underwent adipogenesis in the absence of media-based cues. In vivo, animal modeling showed vasculature formation followed by perilipin A-positive tissue segments. Allograft adipose matrix maintained soft-tissue volume in the dorsal wrist in a 4-month investigation with no severe adverse events, becoming palpably consistent with subcutaneous adipose. CONCLUSIONS: Subcutaneous implantation of allograft adipose matrix laden with retained angiogenic and adipogenic factors served as an inductive scaffold for sustaining adipogenesis. Tissue incorporation assessed histologically from both the subcutaneous injection site of the athymic nude mouse over 6 months and human dorsal wrist presented adipocyte morphology residing within the injected scaffold.

Real-Time Ultrasound-Assisted Gluteal Fat Grafting.

BACKGROUND: The number of gluteal fat augmentation procedures has increased recently and so has the number of complications. Because of the increased risk of morbidity and mortality when fat is injected intramuscularly, not knowing where fat is injected is concerning. We sought to identify the planes in which fat is injected during the procedure. METHODS: We selected 15 consecutive female patients who desired gluteal fat augmentation. All patients had epidural anesthesia and the gluteal region was infiltrated with a vasoconstrictive solution. With the patient in prone position, an ultrasound probe placed on the buttocks was used to identify the fascial layers. While decanted fat was being injected with a blunt cannula, the images were projected wirelessly to a screen, so that the surgeon and assistant could follow the planes in which the cannula was being introduced and the fat injected. RESULTS: The mean volume of harvested fat was 3533 ml and the mean volume of fat injected per gluteal region was 528 ml. The evaluation of the depth and location of the cannula was performed in real time with the ultrasound, accurately and reliably identifying the planes of fat injection. All injections were subcutaneous. The downsides of this technique were the purchase cost of the ultrasound device, increased surgical time, the need for an assistant to follow the cannula and the probe constantly, and the learning curve. CONCLUSION: Real-time ultrasound-assisted gluteal fat grafting is reliable and may avoid injuring the deep vessels, further decreasing the risks of major complications.

Regulatory Advocacy Update: American Society of Plastic Surgeons Comments in Response to the U.S. Food and Drug Administration Draft Guidance Documents on Human Cell and Tissue Products.

The U.S. Food and Drug Administration released draft guidance documents on human cells, tissues, and cellular and tissue-based products regulations. These proposed guidance documents can impact the practice of plastic surgery in the area of tissue grafting procedures. This article describes the relevant issues in these draft guidance documents, and presents the comments provided to the U.S. Food and Drug Administration by the American Society of Plastic Surgeons.

Demystifying the U.S. Food and Drug Administration: understanding regulatory pathways.

BACKGROUND: The field of plastic surgery has been at the forefront of ideation and innovation. Surgeon scientists today continue to develop novel products that fulfill the needs of the medical community and patients. Part of this process requires the approval from various regulatory agencies and offices, including the U.S. Food and Drug Administration. Unfortunately, medical training does not include regulatory knowledge, and many surgeon scientists find the regulatory pathway and U.S. Food and Drug Administration perplexing, overly complicated, and insurmountable. The authors aim to clearly outline the path of the regulatory process as it pertains to the U.S. Food and Drug Administration and its various jurisdictions that may relate to the plastic surgeon. METHODS: The authors aim to demystify the classification system, 510(k), and Premarket Approval processes for devices; clarify the Investigational New Drug and New Drug Application requirements for drugs; and explain how human cells, tissues, and cellular or tissue-based products are classified and approvals obtained. RESULTS: The structure of the U.S. Food and Drug Administration, its offices, and their roles are delineated, and the complex process of obtaining approval to market devices, drugs, biologics, and combination products is explained in a manner that is broadly useful to innovators whether new or experienced. CONCLUSION: The authors provide information for innovators and inventors developing promising technologies to be more knowledgeable and motivated to embrace the process in a fashion that will potentially save time and errors in U.S. Food and Drug Administration submissions.

Demystifying the U.S. Food and Drug Administration: I. Understanding agency structure and function.

The U.S. Food and Drug Administration is the government agency responsible for oversight of the safety and efficacy of pharmaceuticals and devices, including biologics and devices that combine biologics with other materials. Within the U.S. Food and Drug Administration, the Center for Biologics Evaluation and Research is specifically responsible for the evaluation and approval of biological products. This department of the U.S. Food and Drug Administration has a series of mechanisms in place to aid researchers in the process of developing new biologics. This article outlines the study phases involved in developing new biologics and how the Center for Biologics Evaluation and Research and investigators can work together to facilitate this process. It also discusses issues specific to biologics that have been encountered in the past and that investigators should consider when developing and obtaining approval for new biologics. The equivalent center within the U.S. Food and Drug Administration for approving medical devices is the Center for Devices and Radiological Health. The equivalent process of development and approval of medical devices is similarly discussed. Finally, essential contacts for investigators within the Center for Biologics Evaluation and Research and the Center for Devices and Radiological Health are provided.

A report of the ASPS Task Force on regenerative medicine: opportunities for plastic surgery.

In 2011, the American Society of Plastic Surgeons (ASPS) created the Task Force on Regenerative Medicine to address the Society's strong interest in the emerging field of regenerative medicine, particularly cell- and tissue-based therapies applicable to plastic surgery procedures. The Task Force's U.S. Food and Drug Administration's Workgroup is informing ASPS interactions with the U.S. Food and Drug Administration's Center for Biologics Evaluation and Research. Engaging in dialogue with the agency to determine which research protocols will produce scientific data necessary to determine safety and efficacy for regenerative cellular therapies can allow research to be targeted to gather data that prove safety and efficacy of specific categories of therapies and/or products. This article reviews the regulatory backdrop of regenerative medicine, briefly reviews the history of regenerative medicine, and then looks at current research and potential future areas of research and clinical application. The historic ability of plastic surgeons to innovate and apply translational research positions the specialty of plastic surgery as a strong leader in clinical applications of regenerative medicine therapies.

First global summit of national plastic surgery societies: joint statement.

This article constitutes the joint statement from the plastic surgery societies of Australia, Belgium, Brazil, France, Great Britain, New Zealand, South Africa, South Korea, Switzerland, and the United States. It reviews the background, history, and participants of the First Global Summit of National Plastic Surgery Societies, held on October 1, 2010, in Toronto, Canada. In addition, it documents the highlights of the meeting, focuses on areas of agreement among the representative societies, and looks forward to future actions of the participating societies.

Risks and opportunities for plastic surgeons in a widening cosmetic medicine market: future demand, consumer preferences, and trends in practitioners' services.

BACKGROUND: The American Society of Plastic Surgeons and the American Society for Aesthetic Plastic Surgery launched a joint Cosmetic Medicine Task Force to address the growing trend of non-plastic surgeons entering the cosmetic medicine field. The task force commissioned two surveys in 2007 to determine consumer attitudes about choosing cosmetic medicine providers and to learn about the cosmetic services that plastic surgeons offer. METHODS: The first survey obtained responses from 1015 women who had undergone a cosmetic procedure or were considering having one within 2 years. The second survey obtained responses from 260 members of the two societies. RESULTS: Compared with other practitioners, plastic surgeons enjoy higher rates of satisfaction among their patients who undergo noninvasive procedures. Injectables present a particularly promising market for plastic surgeons. Half of consumers surveyed said they were very concerned about complications associated with injectables, and generally, the higher the perceived risk of the procedure, the higher the likelihood that a patient would choose a plastic surgeon to perform it. In addition, injectables were among the noninvasive treatments most frequently being considered by consumers. However, almost half of consumers said that if they had a positive experience with a non-plastic surgeon core provider for a noninvasive procedure, that physician would likely be their first choice for a surgical procedure. CONCLUSIONS: These findings suggest that plastic surgeons, and especially those who are building young practices, must expand their offerings of nonsurgical cosmetic services to remain at the core of the cosmetic medicine field.

Use of regenerative human acellular tissue (AlloDerm) to reconstruct the abdominal wall following pedicle TRAM flap breast reconstruction surgery.

BACKGROUND: Harvest of transverse rectus abdominis musculocutaneous (TRAM) flaps for breast reconstruction leaves a variable defect in the anterior rectus fascia. Inadequate closure of the defect could lead to the development of hernia or abdominal wall bulging. Various techniques have been developed to reduce the incidence of hernia and abdominal wall bulging. The authors describe a novel technique of using a regenerative human acellular matrix (AlloDerm) as a fascial substitute in closing the defect. METHODS: Fifty-four consecutive patients who opted for pedicle TRAM flap procedures for breast reconstruction postmastectomy were scheduled for donor-site repair with the use of AlloDerm. AlloDerm was placed interpositionally as an inlay graft to mimic the anterior rectus fascia. RESULTS: Hernia or infection did not develop in any of the patients. There was a greater incidence of seroma and bulging among the first 18 patients, with eight seromas (44.4 percent) and six bulges (33.3 percent). When the technique was ameliorated in the next 36 patients, there was a reduction in the incidence of seromas (16.7 percent, p = 0.03) and bulges (16.7 percent, p = 0.17). Of the three patients who experienced wound dehiscence, partial AlloDerm exposure occurred in two, but was resolved without further consequences. Biopsy specimens of AlloDerm, obtained 12 and 14 months after TRAM donor-site repair, showed full tissue integration. The cell density, vasculature, and collagen orientation in the biopsies were consistent with abdominal fascia tissue. CONCLUSION: Based on these results, the authors recommend the use of AlloDerm as an alternative option for abdominal fascia closure after TRAM flap harvest for breast reconstruction.