Active Vitamin D3 (Calcitriol) Increases Adipose Graft Retention in a Xenograft Model.

BACKGROUND: Autologous fat grafting, although broadly indicated, is limited by unsatisfactory retention and often requires multiple procedures to achieve durable outcomes. Graft survival is strongly influenced by the magnitude and duration of post-engraftment ischemia. Calcitriol is a pleiotropic, safe nutrient with cell-specific influence on viability and metabolic flux. OBJECTIVES: Evaluate the efficacy of activated vitamin D3 (calcitriol) in improving grafting outcomes and examine its mechanisms. METHODS: Lipoaspirate was collected for ex vivo culture (7 unique donors), in vitro bioenergetic analysis (6 unique donors), and in vivo transplantation (5 unique donors). Ex vivo samples were incubated for up to 2 weeks before extraction of the stromal vascular fraction (SVF) for viability or flow cytometry. SVF was collected for Seahorse (Agilent; Santa Clara, CA) analysis of metabolic activity. Human endothelial cell lines were utilized for analyses of endothelial function. In vivo, samples were implanted into athymic mice with calcitriol treatment either (1) once locally or (2) 3 times weekly via intraperitoneal injection. Grafts were assessed photographically, volumetrically, and histologically at 1, 4, and 12 weeks. Hematoxylin and eosin (H&E), Sirius red, perilipin, HIF1α, and CD31 tests were performed. RESULTS: Calcitriol-treated lipoaspirate demonstrated dose-dependent increases in SVF viability and metabolic reserve during hypoxic stress. Calcitriol treatment enhanced endothelial mobility ex vivo and endothelial function in vitro. In vivo, calcitriol enhanced adipocyte viability, reduced fibrosis, and improved vascularity. Continuous calcitriol was sufficient to improve graft retention at 12 weeks (P < .05). CONCLUSIONS: Calcitriol increased fat graft retention in a xenograft model. Calcitriol has potential to be a simple, economical means of increasing fat graft retention and long-term outcomes.

The Impact of Massive Weight Loss on Psychological Comorbidities: A Large, Retrospective Database Review.

BACKGROUND: The obese population has a higher incidence of mood disorders compared to individuals with normal body mass index (BMI). A better understanding of the unique psychosocial challenges faced by this patient population will allow physicians to better optimize patient psychosocial support systems perioperatively, as well as help the patient to maintain appropriate expectations. METHODS: A large, retrospective database of 1135 patients with greater than 50 pounds of weight loss was reviewed. Data were analyzed using a multinomial regression model to determine the influence of psychosocial factors on the incidence of depression and anxiety. RESULTS: Prior to massive weight loss, patients reported an overall incidence of depression and anxiety of 42.5% and 26.3%, respectively. Following massive weight loss, the incidence of depression decreased to 32.3% and the incidence of anxiety decreased to 22.0%. Patients with spousal support and with positive self-image were more likely to experience resolution of depression. Patients with positive self-image were likely to experience resolution of anxiety. Resolution of medical comorbidities correlated with a decrease in the rate of depression. CONCLUSION: Depression and anxiety are prevalent in the massive weight loss patient population undergoing body contouring surgery. Support systems are a vital resource for patients with psychological comorbidities undergoing massive weight loss. Patients who have a positive self-image of themselves are more likely to experience resolution of psychological comorbidities. Physicians should consider recommending support groups and/or counseling in patients who have poor support and negative self-image. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

The Role of Fat Grafting in Alleviating Neuropathic Pain: A Critical Review of the Literature.

BACKGROUND: Neuropathic pain is one of the more severe types of chronic pain and presents a great challenge as response to medical therapy remains often unpredictable. With the opioid epidemic and the search for ways to avoid narcotics, physicians are seeking other modalities to treat neuropathic pain. In recent years, surgeons have explored various surgical avenues to improve outcomes. The aim of this review was to evaluate the current clinical evidence regarding the efficacy of fat grafting for the treatment of neuropathic pain. METHODS: A critical review was conducted to examine the current clinical evidence of fat grafting as a therapy for neuropathic pain caused by neuromas, peripheral neuralgia, migraine and headaches, neuropathic scar pain, and postmastectomy pain syndrome. RESULTS: The precise mechanism role of fat grafting in modulating neuropathic pain remains unclear, but it appears to reduce pain levels through the anti-inflammatory effects of adipose-derived stem cells and mechanical cushioning by fat. CONCLUSIONS: Fat grafting is an emerging therapy for chronic neuropathic pain of various etiologies. Although promising results have been reported, sample size and level of evidence of current studies are low. The encouraging results, however, are worthy of further clinical and scientific study. The minimally invasive nature of fat grafting and favorable risk profile make this an attractive therapy for neuropathic pain.

Quick Calculation of Breast Resection Mass Using the Schnur Scale.

In 1991, Dr Paul Schnur and his colleagues published an article correlating the weight of breast tissue to be removed in a breast reduction operation with the total body surface area (BSA) of the patient. They presented a very cogent argument for selecting three groups of patients: those with medical indications for operation, those who merit review, and those whose operation could be considered cosmetic. The Schnur Sliding Scale is widely used by insurance companies in the western United States in the process of preauthorizing breast reduction operations, and its use may be spreading eastward. The Schnur group presented a nomogram for calculating BSA and a scale in the form of a table for guiding a determination of whether the patient is a reconstructive patient as opposed to an aesthetic patient. We have combined the scale and the BSA nomogram for a simplified nomogram calculator that facilitates rapid determination of anticipated tissue weight of resection for a patient of a given size. This calculator yields the required weight of tissue to remove with just knowledge of the patient's height and weight and the use of a straight edge. We demonstrate and compare performance of this calculation by hand and by nomogram. There is ample evidence that the practice of applying the Schnur Sliding Scale may be prohibitive to symptomatic patients seeking reduction mammaplasty and should be abandoned. While this practice continues, our simplified Schnur Sliding Scale nomogram is meant to help easily determine the insurer-required minimum breast resection weight and thereby both improve patient counseling prior to planning surgery and assist the surgeon with achieving insurer reimbursement for the procedure while avoiding rejected claims.

Surgical Management of the Giant Pannus: Indications, Strategies, and Outcomes.

The obesity pandemic continues to produce an inexorable increase in the number of patients requiring surgical treatment of obesity and obesity-related complications. Along with this growing number of patients, there is a concomitant increase in the complexity of management. One particular example is the treatment of patients with an exceptionally large and morbid pannus. In this report, we detail the management of seven patients suffering from a giant pannus. Medical and surgical variables were assessed. A quality of life questionnaire was administered pre- and postoperatively. All seven patients suffered some obesity-related medical morbidity and six of seven (86%) had local complications of the giant pannus. Each patient underwent giant panniculectomy [resection weight > 13. 6 kg (30 lb)]. The mean resection weight was 20.0 kg. Four of seven (57%) patients experienced postoperative complications, with two (29%) requiring re-operation and blood transfusion. Six patients were available for long-term follow-up; 100% of participants indicated an increased quality of life while five (83%) reported additional postoperative weight loss, increase in exercise frequency and walking ability, and improved ability to work. Our results indicate that giant panniculectomy is a challenging and risky procedure, but careful patient selection and intraoperative scrutiny can ameliorate these risks and afford patients a dramatically improved quality of life. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Adipose derived delivery vehicle for encapsulated adipogenic factors.

Hydrogels derived from adipose tissue extracellular matrix (AdECM) have shown potential in the ability to generate new adipose tissue in vivo. To further enhance adipogenesis, a composite adipose derived delivery system (CADDS) containing single- and double-walled dexamethasone encapsulated microspheres (SW and DW Dex MS) has been developed. Previously, our laboratory has published the use of Dex MS as an additive to enhance adipogenesis and angiogenesis in adipose tissue grafts. In the current work, AdECM and CADDS are extensively characterized, in addition to conducting in vitro cell culture analysis. Study results indicate the AdECM used for the CADDS has minimal cellular and lipid content allowing for gelation of its collagen structure under physiological conditions. Adipose-derived stem cell (ASC) culture studies confirmed biocompatibility with the CADDS, and adipogenesis was increased in experimental groups containing the hydrogel scaffold. In vitro studies of AdECM hydrogel containing microspheres demonstrated a controlled release of dexamethasone from SW and DW formulations. The delivery of Dex MS via an injectable hydrogel scaffold combines two biologically responsive components to develop a minimally, invasive, off-the-shelf biomaterial for adipose tissue engineering. STATEMENT OF SIGNIFICANCE: Scientists and doctors have yet to develop an off-the-shelf product for patients with soft tissue defects. Recently, the use of adipose derived extracellular matrix (adECM) to generate new adipose tissue in vivo has shown great promise but individually, adECM still has limitations in terms of volume and consistency. The current work introduces a novel composite off-the-shelf construct comprised of an adECM-based hydrogel and dexamethasone encapsulated microspheres (Dex MS). The hydrogel construct serves not only as an injectable protein-rich scaffold but also a delivery system for the Dex MS for non-invasive application to the defect site. The methods and results presented are a progressive step forward in the field of adipose tissue engineering.

Peptide-surface modification of poly(caprolactone) with laminin-derived sequences for adipose-derived stem cell applications.

Human adipose tissue has been recognized as a source of adult stem cells for tissue engineering applications such as bone, cartilage, and soft tissue repair. For the success of these tissue-engineering approaches, a cell delivery vehicle such as a hydrogel or scaffold is required to position the stem cells at the site of need. Surface modification techniques have been instrumental in the development of scaffolds that promote cell-surface interactions. In this study, poly(caprolactone) (PCL), surfaces were modified in order to promote the attachment and proliferation of adipose-derived stem cells (ASCs). RGD, YIGSR, and IKVAV peptide sequences derived from the extracellular matrix protein laminin were each covalently attached to an aminated polymer surface using carbodiimide chemistry. The surface was characterized using scanning electron microscopy (SEM), goniometry and X-ray photoelectron spectroscopy (XPS). The attachment and proliferation of ASCs was assessed on the different peptide-treated surfaces. XPS analysis confirmed the presence of the peptide sequences on the surface of the polymer as indicated by the increase in the nitrogen/carbon ratio on the surface of the polymer. Among all peptide sequences tested, IKVAV-treated surfaces had a significantly greater number of ASCs bound 2 and 3 days after cell seeding. SEM confirmed differences in the morphology of the cells attached to the three peptide-treated surfaces. These results indicate that IKVAV is a suitable peptide sequence for use in surface modification techniques aimed at improving the attachment of ASCs to a tissue-engineered scaffold.