Adipose Graft Research Articles

Regeneration of full thickness common extensor tendon tear after percutaneous microfragmented adipose graft.

Tennis elbow, also commonly known as lateral epicondylitis or common extensor tendinosis, is a common musculoskeletal injury in the adult population. Currently, the standard treatment regimen prescribed for this injury involves a combination of rest, physical therapy, bracing and anti-inflammatory medications. If refractory to these conservative measures, platelet-rich plasma has been shown effective. However, in the case of full thickness tears, surgery has remained the only treatment option until now. We present a case report of a 56-year-old man with a diagnosis of a left large full thickness tear and rupture with retraction of his common extensor tendon (CET) following a corticosteroid injection. The patient was treated with microfragmented adipose transfer. He was re-evaluated around 7weeks and again at 15weeks post-treatment and demonstrated ultrasound evidence of complete bridging and remodeling of his prior full thickness CET tear and resolution of retraction. This case presents a promising option for patients with full thickness CET tears who would like to refrain from or are unable to have surgery. Further research and possible randomized controlled trials are needed to further assess the full efficacy of microfragmented adipose transfer in the treatment of full thickness CET tears.

Lymphatic Vessel-Mediated Attenuation of Persistent Macrophage Infiltration Improves Fat Grafting Outcomes in Mice Models.

Persistent macrophage infiltration may lead to adverse consequences, such as calcifications and nodules in fat grafts. Lymphatic vessels, which transport inflammatory cells, are involved in regulating inflammatory responses. Less is known, however, about lymphatic vessels after fat grafting. The aim of this study was to explore the regulation of fat graft survival by lymphatic vessels. A common adipose graft model was constructed to assess the processes responsible for changes in the number of lymphatic vessels in grafts. Adipose tissue samples from C57/BL6 mice and green fluorescent protein-expressing mice were cross-grafted to determine the source of lymphatic vessels. The number of lymphatic vessels in the grafts was increased by treatment with vascular endothelial growth factor C, and the effects of this increase on fat grafting were evaluated. The number of lymphatic vessels was greater in postgrafted fat than in inguinal fat before transplantation, with lymphatic vessels in these grafts gradually transitioning from donor to recipient sources. Lymphatic vessels grew more slowly than blood vessels during early stages of grafting; during later stages, however, the number of blood vessels declined markedly, with more lymphatic vessels than blood vessels being observed 60 days after grafting. Vascular endothelial growth factor C treatment increased graft lymphatics and distant volume retention, while reducing fibrosis and oil sacs. Lymphatic vessels acted as drainage channels for macrophages, with the degree of sustained macrophage infiltration decreasing with increases in the number of lymphatic vessels. Increasing the number of lymphatic vessels is beneficial for fat graft survival, which may be related to a reduction in prolonged macrophage infiltration.

Differential Secretomes of Processed Adipose Grafts, the Stromal Vascular Fraction, and Adipose-Derived Stem Cells.

There are multiple methods to prepare lipoaspirate for autologous fat transfer; however, graft retention remains unpredictable. The purpose of this study was to compare the cellular and protein composition of adipose grafts and the stromal vascular fraction (SVF) resulting from three common techniques to prepare adipose grafts. Adipose grafts were harvested from healthy donors and processed via three techniques: centrifugation (C), a single-filter (SF) device, and a double-filtration (DF) system. Part of each graft was analyzed or further processed to isolate the SVF. Cell viability, surface markers, cytokine, and growth factors were compared between the graft and SVF as well as adipose-derived stem cells (ASCs). Overall, we found variations across the three processing techniques and among the graft components (ASCs, SVF, and fat). Cell viability within the grafts was similar (94.6%, 92.3%, and 93.6%; P = 0.93). The trend was a greater percentage of ASCs from SF versus DF or centrifugation (6.95%, 4.63%, and 1.93%, respectively, P = 0.06). Adipogenic markers (adiponectin and leptin) were similar among all three grafts (P = 0.45). Markers of tissue remodeling were greatest in the SVF compared with fat and ASCs, regardless of processing technique. There was higher relative expression of MMP-9 (2×), Extracellular matrix metalloproteinase inducer (EMMPRIN) (2.5×), endoglin (5×), and IL-8 (1.5×) in the SVF (P < 0.005). Our study identified differences in cytokine expression in adipose grafts and the SVF, particularly in cytokines important in inflammation and wound healing. These secretomes may impact graft retention and fat necrosis and have the potential implications in cell-assisted lipotransfer. There were no significant differences between the final products of any of the processing techniques.

Advancing Standardization in Fat Graft Survival Studies: Assessing the Superiority of Paraepididymal Fat Graft as a Donor Site.

There is currently no standardization in the field of research on fat grafts in rats, which is one of the most popular topics in plastic surgery. The aim of our study was to demonstrate the effects of selecting paraepididymal fat grafts as the donor area on enhancing the reliability of fat graft studies. In this study, 12 male Sprague-Dawley rats were used to obtain adipose grafts from both inguinal and paraepididymal regions. After measuring the graft weights, they were subjected to histological examination using hematoxylin-eosin staining, as well as immunohistochemical staining with antiperilipin antibody. Purity of the samples, viability of adipose cells, and the presence of lymph nodes within the grafts were analyzed. The purity of adipose cells in graft samples obtained from the paraepididymal region was found to be 98.1% compared with the total sample. In contrast, the purity of adipose cells in graft samples obtained from the inguinal region was 58.37%. Hematoxylin-eosin staining revealed significantly higher adipocyte viability and vascularity in the paraepididymal region compared with the inguinal region (P = 0.0134). Conversely, lymphatic tissue content in samples obtained from the inguinal region was significantly higher compared with paraepididymal adipose tissue samples (P < 0.0001). Immunohistochemical staining with antiperilipin antibody showed a denser and more uniform staining pattern in paraepididymal adipose grafts (P < 0.0001). Using paraepididymal fat, devoid of lymphatic tissue, naturally eliminates 2 critical biases (estrogen and lymphatic tissue), enhancing the standardization and reliability of fat graft survival studies.

NPTX1 Mediates the Facilitating Effects of Hypoxia-Stimulated Human Adipocytes on Adipose-Derived Stem Cell Activation and Autologous Adipose Graft Survival Rate.

Autologous adipose tissue is an ideal material for soft tissue filling and transplantation; however, high volumes of fat absorption over time lead to a relatively low overall survival percentage. The survival and differentiation of adipose-derived stem cells (ADSCs) in the transplanted microenvironment might improve adipose graft survival. Adipocytes have been reported to affect ADSC activation. However, its underlying mechanisms remain unclear. Human ADSCs were incubated in a culture medium supplemented with hypoxic or normoxic conditioned culture medium (CM) derived from human adipocytes. Neuronal Pentraxin 1 (NPTX1) was overexpressed or knocked down in human adipocytes using an overexpression vector (NPTX1 OE) or small interfering RNA (siRNA) transfection, respectively. ADSC differentiation and paracrine secretion were assessed. Nude mice were implanted with human adipocytesand ADSCs. The adipose tissue was subsequently evaluated by histological analysis. CM from hypoxic-stimulated human adipocytes significantly facilitated the differentiation ability and paracrine levels of ADSCs. NPTX1 was significantly up-regulated in human adipocytes exposed to hypoxic conditions. In vitro, CM derived from hypoxia-stimulated human adipocytes or NPTX1-overexpressing human adipocytes exposed to normoxia promoted ADSC differentiation and paracrine; after silencing NPTX1, the facilitating effects of hypoxia-treated human adipocytes on ADSC activation were eliminated. Similarly, in vivo, the NPTX1 OE + normoxia-CM group saw improved histological morphology and fat integrity, less fibrosis and inflammation, and increased vessel numbers compared with the OE NC + normoxia-CM group; the adipocyte grafts of the si-NC + hypoxia-CM group yielded the most improved histological morphology, fat integrity, and the most vessel numbers. However, these enhancements of ADSC activation and adipose graft survival were partially abolished by NPTX1 knockdown in human adipocytes. NPTX1 might mediate the facilitating effects of hypoxia-stimulated human adipocytes on ADSC activation, thereby improving adipose tissue survival rate after autologous fat transplantation and the effectiveness of autologous fat transplantation through promoting ADSC activation. 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 .

Brown Adipose Tissue Promotes Autologous Fat Grafts Retention Possibly Through Inhibiting Wnt/β-Catenin Pathway.

In plastic surgery, autologous fat grafts (AFG) play an important role because of their abundant supply, biocompatibility, and low rejection rate. However, the lower retention rate of fat grafts limits their widespread use. Brown adipose tissue (BAT) can promote angiogenesis and regulate the level of associated inflammation. This study explored whether BAT has a facilitative effect on fat graft retention. We obtained white adipose tissue (WAT) from c57 mice and combined it with either BAT from c57 mice or phosphate-buffered saline (PBS) as a control. These mixtures were injected subcutaneously into the back of thymus-free nude mice. After 12 weeks, fat grafts were harvested, weighed, and analyzed. We found that the BAT-grafted group had higher mass retention, more mature adipocytes, and higher vascularity than the other group. Further analysis revealed that BAT inhibited M1 macrophages; down-regulated IL-6, IL-1β, and TNF-β; upregulated M2 macrophages and Vascular endothelial growth factor-A (VEGFA); and promoted adipocyte regeneration by inhibiting the Wnt/β-catenin pathway, which together promoted adipose graft retention. The study demonstrated that BAT improved adipose graft retention by promoting angiogenesis, inhibiting tissue inflammation levels and the Wnt/β-catenin pathway. 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.

Repurposing Decellularized Lung to Generate Vascularized Fat.

Conventional therapies to address critically sized defects in subcutaneous adipose tissue remain a reconstructive challenge for surgeons, largely due to the lack of graft pre-vascularization. Adipose tissue relies on a dense microvasculature network to deliver nutrients, oxygen, nonadipose tissue-derived growth factors, cytokines, and hormones, as well as transporting adipose tissue-derived endocrine signals to other organ systems. This chapter addresses these vascularization issues by combining decellularized lung matrices with a step-wise seeding of patient-specific adipose-derived stem cells and endothelial cells to develop large-volume, perfusable, and pre-vascularized adipose grafts.

CD304 + adipose tissue-derived mesenchymal stem cell abundance in autologous fat grafts highly correlates with improvement of localized pain syndromes.

Surgery, burns or surgery-free accident are leading causes of scars with altered tissue consistency, a reduced degree of motion and pain. Autologous fat grafting can dramatically improve tissue consistency and elasticity but less frequently results in the reduction of pain. Therefore, we analyzed different cell populations present within the adipose tissue to be engrafted and correlated them with the reduction of pain after surgery. Here, we identify a population of CD3 - CD4 - CD304 + cells present in grafted adipose tissue, whose abundance highly correlates with pain improvement shortly after surgery ( r2 = 0.7243****) as well as persistently over time (3 months later: r2 = 0.6277****, 1 year later: r2 = 0.5346***, and 4 years later: r2 = 0.5223***). These cells are characterized by the absence of the hematopoietic marker CD45, whereas they express CD90 and CD34, which characterize mesenchymal stem cells (MSCs); the concomitant presence of CD10 and CD73 in the plasma membrane supports a function of these cells in pain reduction. We deduce that the enrichment of this adipose tissue-derived MSC subset could enhance the therapeutic properties of adipose grafts and ameliorate localized pain syndromes.

Effect of Combined Bone Marrow Aspirate, Lipoaspirate, and Platelet-Rich Plasma Injections on Pain, Function, and Perceived Change Amongst Individuals with Glenohumeral Osteoarthritis

Purpose: This study was conducted to investigate the efficacy of a combined minimally processed bone marrow aspirate (BMA), adipose graft, and leukocyte-rich platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with glenohumeral osteoarthritis (GHOA) and record any complications or adverse events associated with the protocol. Methods: Ten adults (mean age 65 years) previously recalcitrant to conservative care with clinical and radiographic evidence of GHOA were included. At the initial visit, patients were assessed for eligibility of treatment. All patients were assessed pre- and post-treatment with numerical pain rating and patient-specific functional scales (PSFS). All study participants were treated with 4–6 ml of PRP, 6 ml adipose graft, and 12 ml of BMA, which were administered via a landmark-based anterior intra-articular injection. Patients were requested to return twice over 4-week intervals for booster PRP injections. At each follow-up, the GROC and prior outcome measures were completed. Results: Patients returned after an average of 27 days for first (F1) and 68 days for the second (F2) PRP injection. Friedman Chi Square analysis indicated significant improvements in best and worse pain and PSFS from baseline initial visit to F1 and F2 (P ≤ .002). Post-hoc Wilcoxon signed-rank testing with Bonferroni correction (α = 0.017) identified significant improvements from baseline to F1 and F2 for the PSFS (P ≤ 0.012). Improvements in best and worse pain were significant at F2 (P ≤ 0.016), not F1 (P ≥ 0.02), compared to baseline. Effect sizes were large, ranging from r = 0.57 to 0.84 for pain and function. Improvements in pain, GROC, and PSFS met minimum clinically important differences at F2 based on previously validated clinimetrics. The only adverse events reported are related to administration of injectate that was temporary and managed in all cases with over-the-counter analgesics. Conclusion: A minimally processed adipose graft with BMA and three PRP injections improved pain and function among individuals with GHOA who were recalcitrant to conservative care. Although significant functional improvement at both follow-up points occurred, clinically important and significant changes in pain did not occur until F2. A one-group design and multimodal approach limit generalization of results. Level of Evidence: IV

Strategies to Improve AFT Volume Retention After Fat Grafting.

Autologous fat grafting has gained increasing popularity used in plastic surgery as a strategy to improve functional and aesthetic outcome. However, variable augmentation results have concerned surgeons in that volume loss of grafted fat reported fluctuates unsteadily. An optimal technique that clinically maximizes the long-term survival rate of transplantation is in urgent need to be identified. The PubMed/MEDLINE database was queried to search for animal and human studies published through March of 2022 with search terms related to adipose grafting encompassing liposuction, adipose graft viability, processing technique, adipose-derived stem cell, SVF and others. 45 in vivo studies met inclusion criteria. Theprincipal of ideal processing technique is effective purification of fat and protection of tissue viability, such as gauze rolling and washing-filtration devices. Cell-assisted lipotransfer including SVF,SVF-gel and ADSCs significantly promotes graft retention via differentiation potential and paracrine manner. ADSCs induce polarization of macrophages to regulate inflammatory response, mediate extracellular matrix remodeling and promote endothelial cell migration and sprouting, and differentiate into adipocytes to replace necrotic cells, providing powerful evidence for the benefits and efficacy of cell-assisted lipotransfer. Based on the current evidence, the best strategy can not be decided.Cell-assisted lipotransferhas great potential for use in regenerative medicine. But so far mechanically prepared SVF-gel is conducive to clinical promotion. PRP as endogenous growth factor sustained-release material shows great feasibility. 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 .

Microfractured Adipose Tissue Graft for the Advanced Treatment of Non-Healing Cutaneous Fistulas

Chronic cutaneous non-healing fistulas very often are dehiscences of surgical or traumatic wounds that do not repair properly and progressively undergo intrafistular and perifistular fibrosis. The fibrous tissue constitutes a natural barrier to the progression of the fistula repair process and represents the major cause of non-healing and chronicization even in a context of proper vascularization. The microfractured autologous adipose graft allows to provide the tissues involved in the fibrotic process with a regenerative stimulus by MSCs (mesenchymal stem cells) contained in adipose clusters of 0.3 mm. In this context, MSCs are able to secrete cytokines with antibiotic, antifibrotic, angiogenic and analgesic effects. The micro-fragmentation technique guarantees a high regenerative effect, as the MSCs are not isolated enzymatically with the simultaneous destruction of the adipose tissue. The micro-fragmentation allows the maintainance of the structure of the adipose cluster including microvessels and allows it to amplify by 6000 times the active surface that exposes the MSCs. Our experience with the mechanical microfracturing method of lipoaspirate consists of 41 treatments. In 7 cases the graft was performed due to the presence of a non-healing cutaneous fistula, which lasted from 128 to 243 days. In 6 cases we achieved immediate repair and closure of the fistula while in one case the procedure failed. The purpose of the paper is to describe in detail our experience by an accurate description of the implemented method of the used device accompanied by the document with adequate photographic documentation.

Electrophysiological effects of adipose graft transposition procedure (AGTP) on the post-myocardial infarction scar: A multimodal characterization of arrhythmogenic substrate.

ObjectiveTo assess the arrhythmic safety profile of the adipose graft transposition procedure (AGTP) and its electrophysiological effects on post-myocardial infarction (MI) scar.BackgroundMyocardial repair is a promising treatment for patients with MI. The AGTP is a cardiac reparative therapy that reduces infarct size and improves cardiac function. The impact of AGTP on arrhythmogenesis has not been addressed.MethodsMI was induced in 20 swine. Contrast-enhanced magnetic resonance (ce-MRI), electrophysiological study (EPS), and left-ventricular endocardial high-density mapping were performed 15 days post-MI. Animals were randomized 1:1 to AGTP or sham-surgery group and monitored with ECG-Holter. Repeat EPS, endocardial mapping, and ce-MRI were performed 30 days post-intervention. Myocardial SERCA2, Connexin-43 (Cx43), Ryanodine receptor-2 (RyR2), and cardiac troponin-I (cTnI) gene and protein expression were evaluated.ResultsThe AGTP group showed a significant reduction of the total infarct scar, border zone and dense scar mass by ce-MRI (p = 0.04), and a decreased total scar and border zone area in bipolar voltage mapping (p < 0.001). AGTP treatment significantly reduced the area of very-slow conduction velocity (<0.2 m/s) (p = 0.002), the number of deceleration zones (p = 0.029), and the area of fractionated electrograms (p = 0.005). No differences were detected in number of induced or spontaneous ventricular arrhythmias at EPS and Holter-monitoring. SERCA2, Cx43, and RyR2 gene expression were decreased in the infarct core of AGTP-treated animals (p = 0.021, p = 0.018, p = 0.051, respectively).ConclusionAGTP is a safe reparative therapy in terms of arrhythmic risk and provides additional protective effect against adverse electrophysiological remodeling in ischemic heart disease.

Soft Tissue Reconstruction Strategy of Spontaneous Calcaneal Fracture in a Patient with Diabetic Penetrating Foot Ulcer

Background: Spontaneous pathologic fractures of the calcaneum in diabetic patients are rarely described in the literature. The pathologic fractures following osteomyelitis represent a possibly limb-threatening condition and if associated with a concomitant calcaneal ulcer, they present defiance for the surgeon and furthermore an outstandingly challenging condition to handle. Methods: A 61-year-old diabetic female patient on insulin therapy has been treated for a penetrating foot ulcer. In sequence the following procedures were carried out: Negative pressure wound therapy with instillation and dwell time (NPWTi-d), Negative Pressure Wound Therapy (NPWT), arterial percutaneous angioplasty (PTA), calcanectomy and temporary arthrodesis, application of Dermal Regeneration Template (DRT) and transplantation of microfractured autologous adipose graft (LIPOGEMS®), treatment of residual dehiscence with physical cold plasma (kINPen®MED). Results: The patient completely healed within 20 months and was able to walk without further aids. Conclusion: The authors point to the promptness within the treatment of pathologic calcaneal fractures, whether throughout the usage of technical devices targeting the reduction of the bacterial load and stimulation of healthy tissue, like in NPWTi-d and kINPen®MED. The use of a dermal regeneration template followed by skin grafting enriched with autologous microfractured adipose tissue (LIPOGEMS®), therefore represents today the most advanced regenerative surgical procedures.

Variability in Patient-Incurred Costs and Protocols of Regenerative Medicine Procedures for Musculoskeletal Conditions in the United States.

Background: The use of regenerative medicine as an "off label" treatment for musculoskeletal conditions has increased in recent years. However, the literature is sparse regarding the costs of these treatments to patients. Purposes: We sought to determine the patient-incurred costs for regenerative medicine treatments performed by physicians for musculoskeletal conditions in the United States, according to primary specialty, geographic region, practice setting, and years in practice. We also sought to characterize pre- and posttreatment protocols and image guidance use. Methods: We performed a cross-sectional study with data collection occurring between April 2020 and April 2021. It began with the distribution of an online survey through an email campaign by the American College of Sports Medicine to its members. Approximately 90 emails were sent by our research team as well. Throughout the year, various participant recruitment methods were used (through Twitter, for example). Survey data included physician demographics, practice/training information, types/costs of regenerative medicine treatments performed, and pre-/postprocedure protocols. Results: One hundred physicians who self-reported performing standalone regenerative medicine procedures participated in this online survey. According to the responses, the most common treatments performed were platelet-rich plasma (PRP; 100%), bone marrow concentrate (BMC; 41%), microfragmented adipose grafting (36%), prolotherapy (33%), and bone marrow aspirate (BMA; 21%) administered to the peripheral joints, tendons/muscles, ligaments, and/or spine. Overall, the respondents reported large variations in treatment costs to patients; BMA and BMC were the most expensive and had the largest ranges in costs for all anatomical locations. Costs for PRP were lower than those for BMA and BMC, with less variation. Physicians in private practice reported higher PRP, BMC, and BMA costs in the peripheral joints than those in academic settings. Most physicians recommended avoiding non-steroidal anti-inflammatory drugs pre- and postprocedure, and 74% recommended physical therapy postprocedure. Conclusions: Findings from a survey of physicians who provide regenerative medicine procedures as off-label treatment for musculoskeletal conditions suggest that there is variation in related patient-incurred costs. Future studies should explore associations between treatment costs and outcomes.

Adipose-Derived Stem Cells Exosomes Improve Fat Graft Survival by Promoting Prolipogenetic Abilities through Wnt/β-Catenin Pathway.

Autologous fat grafting has been widely used in plastic surgery in recent years, but the unstable retention of fat graft has always been a key clinical problem. Adipose tissue has poor tolerant to ischemia, so the transplanted adipose tissue needs to rebuild blood supply at an early stage in order to survive stably. Our previous study has found that comparing to human foreskin fibroblast exosome (HFF-Exo), human adipose-derived stem cells exosome (hADSC-Exo) can significantly improve the proliferation of vascular endothelial cells and the angiogenic effect of artificial dermal preconstructed flaps. Therefore, the ability of hADSC-Exo to improve the retention of adipose grafts and its potential regenerative mechanism aroused our strong interest. In this study, we applied hADSC-Exo and HFF-Exo to adipose grafts and explored the potential regeneration mechanism through various means such as bioinformatics, immunofluorescence, immunohistochemistry, and adipogenic differentiation. The results showed that hADSC-Exo can significantly promote grafts angiogenesis and adipogenic differentiation of ADSC to improve the retention of fat grafts and may downregulate the Wnt/β-catenin signaling pathway to promote the adipogenic differentiation. In summary, our results provide a theoretical basis for the clinical translation of hADSC-Exo in fat grafting.

Cardiac reparative therapy with adipose graft transposition procedure (AGTP) improves electrophysiological remodeling of chronic myocardial infarction

Abstract Background Cardiac regeneration is a promising therapeutic option for patients with prior myocardial infarction (MI). Adipose graft transposition procedure (AGTP) is a cardiac reparative therapy consisting of the transposition of a vascularized adipose flap from the autologous pericardium over the epicardial scar area, which has shown to reduce the infarct size and improve the left ventricular function. Purpose To assess the impact of the AGTP on the electrophysiological remodeling of the post-MI scar by means of electrophysiological study (EPS), high density (HD) mapping, and 3D contrast-enhanced MRI (ceMRI). Methods A lateral MI was induced in 14 Landrace X Large White pigs by coil deployment at the first marginal branch of the circumflex artery. A 3D ceMRI, EPS and endocardial HD mapping were performed 2 (baseline) and 6 weeks post-MI (30 day post-treatment). Subjects were randomized to AGTP (n=8) or sham surgery (n=6) following baseline tests. Voltage and activation maps were blindly analyzed off-line with self-customized ParaView-based software. ceMRI was post-processed with ADAS3D. Conventional bipolar and unipolar voltage cut-offs were used (0.5–1.5mV and 6.7mV, respectively). Conduction velocity (CV) was determined for every pair of contiguous points. Areas of CV were quantified for every 0.2m/s steps (&amp;lt;0.2 - 4 m/s). Results At follow-up, and compared to the sham group, the AGTP group showed a significant reduction of the border zone area in both bipolar voltage mapping (−18±50% vs +10±144%, p=0.043) and ceMRI (−2.0±1.7 vs +1.1±2.8g; p=0.047), as well as a reduction in dense scar mass by ceMRI (−1.1±0.7g vs. +0.6±0.9 g, p=0.001). The AGTP group had a significant reduction of the size of very-slow CV areas (&amp;lt;0.2 m/s), compared to the sham group (−3.5±3.4 vs. +1.5±3.8 mm2, p=0.022), without differences in other CV ranges. EPS did not induce ventricular tachycardia in any subject at baseline, and only in 1 of the sham group at the follow-up. Conclusions Cardiac reparative therapy with AGTP of post-MI scar reduced the size of border zone tissue and very-slow conduction zones and could provide a protective effect against arrhythmic events in ischemic heart disease. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FIS grant - Instituto de Salud Carlos III

Engineering a 3D Vascularized Adipose Tissue Construct Using a Decellularized Lung Matrix.

Critically sized defects in subcutaneous white adipose tissue result in extensive disfigurement and dysfunction and remain a reconstructive challenge for surgeons; as larger defect sizes are correlated with higher rates of complications and failure due to insufficient vascularization following implantation. Our study demonstrates, for the first time, a method to engineer perfusable, pre-vascularized, high-density adipose grafts that combine patient-derived adipose cells with a decellularized lung matrix (DLM). The lung is one of the most vascularized organs with high flow, low resistance, and a large blood–alveolar interface separated by a thin basement membrane. For our work, the large volume capacity within the alveolar compartment was repurposed for high-density adipose cell filling, while the acellular vascular bed provided efficient graft perfusion throughout. Both adipocytes and hASCs were successfully delivered and remained in the alveolar space even after weeks of culture. While adipose-derived cells maintained their morphology and functionality in both static and perfusion DLM cultures, perfusion culture offered enhanced outcomes over static culture. Furthermore, we demonstrate that endothelial cells seamlessly integrate into the acellular vascular tree of the DLM with adipocytes. These results support that the DLM is a unique platform for creating vascularized adipose tissue grafts for large defect filling.

QS5: Cryopreserved Adipose for Hypodermal Augmentation After Full-thickness Burns

Purpose:Burn and blast injuries to the face and extremities are highly morbid injuries affecting quality of life, ability to work, and psychosocial well-being. Without exception, extensive burn injuries require surgical debridement, with standard of care reconstruction involving autologous skin grafting to restore cutaneous integrity. This treatment modality is limited in extensive burns or in highly visible areas by lack of donor site and/or soft tissue deficits resulting in significant disfigurement. Hypodermal restoration via autologous adipose transplantation provides padding for the overlying skin, helps restore native features, and enhances contour and texture. However, this technique is limited by graft retention and often requires multiple rounds of grafting and consequently, multiple rounds of surgery, each with separate anesthesia, to achieve adequate results. The goal of this study was to demonstrate the therapeutic validity and efficacy of utilizing cryopreserved adipose to avoid multiple liposuction events when serial skin and fat grafting procedures are performed to restore epidermal, dermal, and hypodermal integrity after full-thickness burn.Methods:Adipose was collected from female Yorkshire swine and processed day-of-collection for immediate cryopreservation. This adipose was preserved for 3 months prior to initiation of the next stage of the experiment. After three-month elapse, female Yorkshire swine received 16, 4x4 cm full-thickness burns using an electric brand. After 48 hours, eschar was removed down to fascia. Skin grafts were collected as split-thickness skin grafts. The pigs were maintained for 8 weeks from time of engraftment and interval serum, photography, ultrasound, and biopsies were collected. At 8 weeks post-engraftment animals were sacrificed and all wounds were collected for histology and proteomic evaluation.Results:Split thickness skin graft take was greater than 95% in all injuries. Adipose grafts from Group B, were noted to remain present and incorporated into the granulation tissue in absence of skin graft with viability confirmed on biopsy. Initial increase in granulation layer thickness was noted in presence of fat graft with Group B vs. Group A. On serial ultrasound assessment, penetrating adipose grafts from Group D were noted to be present without gross resorption at all time points. Cryopreserved adipose remained viable throughout the duration of the experiment with histologic evidence of incorporation at 8 weeks post-operative.Conclusion:Burn and blast injuries predominantly affect military personnel and first responders for whom improvement in protective equipment has decreased mortality without resolving the risk of morbidity to the face or extremities. Hypodermal augmentation with lipografting as part of a strategy of autologous skin grafting addresses contour deficits and skin quality, however is limited by the need for multiple liposuction and grafting procedures, requiring multiple trips to the operating room with increased surgical and anesthetic risk and high economic burden. Here we demonstrate cryopreservation of adipose as an avenue to alleviate that burn.

Hybrid adipose graft materials synthesized from chemically modified adipose extracellular matrix.

Decellularized extracellular matrix (ECM) from tissues is a promising biomaterial that can provide a complex 3D microenvironment capable of modulating cell response and tissue regeneration. In this study, we have integrated the decellularized thiolated adipose-derived ECM, at different concentrations, with polyethylene glycol (PEG) using Michael addition between thiol and acrylate moieties. The potential for this material to support adipogenic differentiation of human adipose-derived stem cells was evaluated by encapsulating cells in hydrogels with increasing concentrations of chemically modified ECM (mECM). Our results demonstrated a positive correlation between the ECM content in the hydrogels and cell proliferation, adipogenic marker expression, and lipid formation and accumulation. Furthermore, we have shown host cell infiltration and enhanced adipogenesis in vivo after implantation. These findings support the graft as a potential alternative for adipose tissue regeneration.

Adipose Grafting for Volume and Scar Release.

Adipose fat grafting (AFG) is a popular technique used to add volume in the face, breasts, and other tissue deficient areas of the body. In terms of scar release, not only has fat provided additional soft tissue coverage but also the relief of pain in scars in those patients suffering from disease processes, such as complex regional pain syndrome with steroid-induced atrophy, burn scars, morphea, and lupus. The purpose of this article is to demonstrate the senior author's technique and outcomes of using AFG in the face and body for treating volume deficiency, atrophic scarring, and deformities.A retrospective chart review of 127 AFG procedures of the face and body from September 2006 to September 2019 was performed. Of these, 14 patients had scar releases performed with fat grafting of areas of scar contracture. Fat was harvested from the abdomen, thighs, and flanks using Toomey syringes or an enclosed power-assisted system with 3.7- or 3.0-mm cannulas. Grafting in small areas, such as the face, was performed with the 0.9-mm blunt cannula.The majority of AFG was completed in the face (45%), followed by breasts (22%), and scar contracture (16%). The mean volume of fat grafted in procedures involving the breasts, buttocks, and face was 102, 182, and 21 mL, respectively. For scar contracture, the mean volume was 38 mL and for deformations, 27 mL. Sixteen percent of the cohort required at least 1 additional AFG procedure to achieve satisfactory results. There were no major complications, such as skin loss, vascular injury, embolization, or blindness. Minor complications, such as erythema, edema, and hematoma at the fat harvest or graft site, did occur and were managed with local measures.Autologous fat grafting has consistently resulted in volume correction. In addition, in patients with autoimmune disorders, burn scars, and retracted scars, not only has there been volume correction but also decreased pain in the area of treatment. In our series of patients, we described our technique of AFG for the face, body, and scar contracture. Our results demonstrate that AFG remains an inexpensive, safe, and effective treatment option to achieve volume.