Adipose Tissue Grafts Research Articles

Clinically Relevant and Precisely Printable Live Adipose Tissue-Based Bio-Ink for Volumetric Soft Tissue Reconstruction.

Autologous fat is widely used in soft tissue reconstruction; however, significant volume reduction owing to necrosis and degradation of the transplanted adipose tissue (AT) remains a major challenge. To address this issue, a novel live AT micro-fragment-based bio-ink (ATmf bio-ink) compatible with precision 3D printing, is developed. Live AT micro-fragments of ≈280µm in size are prepared using a custom tissue micronizer and they are incorporated into a fibrinogen/gelatin mixture to create the ATmf bio-ink. AT micro-fragments exhibit high viability and preserve the heterogeneous cell population and extracellular matrix of the native AT. The developed bio-ink enables precise micropatterning and provides an excellent adipo-inductive microenvironment. AT grafts produced by co-printing the bio-ink with polycaprolactone demonstrate a 500% improvement in volume retention and a 300% increase in blood vessel infiltration in vivo compared with conventional microfat grafts. In vivo engraftment of AT grafts is further enhanced by using a stem cell-laden ATmf bio-ink. Last, it is successfully demonstrated that the bio-ink is enabled for the creation of clinically relevant and patient-specific AT grafts for patients undergoing partial mastectomy. This novel ATmf bio-ink for volumetric soft tissue reconstruction offers a pioneering solution for addressing the limitations of existing clinical techniques.

The effect of exogenous mitochondria in enhancing the survival and volume retention of transplanted fat tissue in a nude mice model

BackgroundDespite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems.ObjectivesThis study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques.MethodsHuman adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining.ResultsMitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group.ConclusionsThis study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.

Autologous Cryopreserved Adipose Tissue Using an Innovative Technique: An In Vitro Biological Characterization

Abstract Background Utilization of autologous adipose tissue transplantation in plastic and orthopedic surgery such as breast reconstruction and intra-articular injection has become an attractive surgical treatment with satisfactory clinical outcomes. Nevertheless, repeated liposuctions necessary to harvest fatty tissue, normally performed with sedation or general anesthesia, may represent a noteworthy concern. Objectives The aim of this study was to demonstrate through an in vitro characterization the validity of the surgical option of cryopreserved autologous adipose tissue harvested in a single shot for repeated graft transfer in breast reconstruction without impairment of cell viability and sterility. Methods Adipose tissue was collected by standard liposuction from patients who needed numerous fat grafting procedures for breast reconstruction. According to an innovative and patented cryopreservation method, autologous adipose tissue was subsequently fractioned in a sterile bag system and frozen at the RER Tissue Bank of the Emilia Romagna Region. Each graft was evaluated for sterility and cell viability immediately after harvesting, and 1, 3, 6, 12, and preliminarily 18 months after cryopreservation and thawing. Results In vitro results showed that after processing, middle-term and long-term cryopreservation, and subsequent thawing, autologous cryopreserved adipose tissue retained absence of bacterial contamination, high cellular viability, and unmodified histomorphological properties, thereby ensuring maintenance of the stromal vascular niche and the filling properties in different multistep surgical procedures. Conclusions In vitro study and sterility assessment showed that autologous cryopreserved adipose tissue grafting is a safe procedure, making it possible to avoid multiple liposuction surgery. No impairment of sterility, cell viability, or morphology was observed over time.

Limited fasciectomy with versus without autologous adipose tissue grafting for treatment of Dupuytren’s contracture (REMEDY): study protocol for a multicentre randomised controlled trial

BackgroundDupuytren’s contracture is a hereditary disorder which causes progressive fibrosis of the palmar aponeurosis of the hand, resulting in digital flexion contractures of the affected rays. Limited fasciectomy is a standard surgical treatment for Dupuytren’s, and the one with the lowest recurrence rate; however, the recurrence is still relatively high (2–39%). Adipose-derived stem cells have been shown to inhibit Dupuytren’s myofibroblasts proliferation and contractility in vitro, as well as to improve scar quality and skin regeneration in different types of surgeries. Autologous adipose tissue grafting has already been investigated as an adjuvant treatment to percutaneous needle fasciotomy for Dupuytren’s contracture with good results, but it was only recently associated with limited fasciectomy. The purpose of REMEDY trial is to investigate if limited fasciectomy with autologous adipose tissue grafting would decrease recurrence compared to limited fasciectomy alone.MethodsThe REMEDY trial is a multi-centre open-label randomised controlled trial (RCT) with 1:1 allocation ratio. Participants (n = 150) will be randomised into two groups, limited fasciectomy with autologous adipose tissue grafting versus limited fasciectomy alone. The primary outcome is the recurrence of Dupuytren’s contracture on any of the treated rays at 2 years postoperatively. The secondary outcomes are recurrence at 3 and 5 years, scar quality, complications, occurrence of algodystrophy (complex regional pain syndrome), patient-reported hand function, and hypodermal adipose tissue loss at 1 year postoperatively in a small subset of patients.DiscussionThe REMEDY trial is one of the first studies investigating limited fasciectomy associated with autologous adipose tissue grafting for Dupuytren’s contracture, and, to our knowledge, the first one investigating long-term outcomes of this treatment. It will provide insight into possible benefits of combining adipose tissue grafting with limited fasciectomy, such as lower recurrence rate and improvement of scar quality.Trial registrationClinicalTrials.gov NCT05067764, June 13, 2022.

DEVELOPING NEXT-GENERATION INJECTABLE ADIPOSE TISSUE GRAFTS FOR SOFT-TISSUE RECONSTRUCTION

IntroductionAutologous fat grafting has favourable potential as a regenerative strategy and is the current gold-standard to repair large contour defects, as needed in breast reconstruction after mastectomy and traumatic soft tissue reconstruction. Clinically, there is a limit on the volume of lipoaspirate which can be utilised to repair a soft-tissue defect. Surgical complications are the result of poor structural fidelity of lipoaspirate and graft resorption as a filling material and are hindered further by poor graft vascularisation. This study aims to develop injectable lipoaspirate-derived adipose tissue grafts with enhanced biologically and clinically-admissible structural and functional properties adopting light photocrosslinking of unmodified lipoaspirate.MethodsPatient-derived lipoaspirate was harvested and crosslinked using novel photoinitiator and exposure to visible light (wavelength 450nm) in surgery, establishing bonds between extracellular matrix (ECM) proteins within the material. The degree of crosslinking was tuned (photoinitiator concentration, light exposure, light intensity) and covalent bond formation measured using mass spectrometry. To predict patient response, SWATH-MS was used to identify differences in patient ECM and crosslinked grafts were implanted in vivo using a subcutaneous mouse model. Functional vessel formation and resorption were quantified using micro-CT and tissue-remodelling was assessed via histology.ResultsThere was an increase in the relative abundance of covalent bonds present with increasing degree of crosslinking. When injected, crosslinked lipoaspirate had better shape fidelity compared with native lipoaspirate – demonstrated by a smaller fibre diameter. Crosslinked lipoaspirate remained viable over long term culture and resulted in more predictable resorption profiles when implanted in vivo.ConclusionsThe crosslinking approach described here is tunable and functional across different patient samples. Improving the structural properties of lipoaspirate through minimal manipulation has clinical utility for the delivery of grafts with higher shape fidelity and therefore increased graft survival when implanted.

Activated Human Adipose Tissue Transplantation Promotes Sensorimotor Recovery after Acute Spinal Cord Contusion in Rats.

Traumatic spinal cord injuries (SCIs) often result in sensory, motor, and vegetative function loss below the injury site. Although preclinical results have been promising, significant solutions for SCI patients have not been achieved through translating repair strategies to clinical trials. In this study, we investigated the effective potential of mechanically activated lipoaspirated adipose tissue when transplanted into the epicenter of a thoracic spinal contusion. Male Sprague Dawley rats were divided into three experimental groups: SHAM (uninjured and untreated), NaCl (spinal cord contusion with NaCl application), and AF (spinal cord contusion with transplanted activated human fat). Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were measured to assess endogenous inflammation levels 14 days after injury. Sensorimotor recovery was monitored weekly for 12 weeks, and gait and electrophysiological analyses were performed at the end of this observational period. The results indicated that AF reduced endogenous inflammation post-SCI and there was a significant improvement in sensorimotor recovery. Moreover, activated adipose tissue also reinstated the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions. This investigation highlights the efficacy of activated adipose tissue grafting in acute SCI, suggesting it is a promising therapeutic approach for spinal cord repair after traumatic contusion in humans.

Micro Fractured Adipose Tissue Graft (Lipogems), Regenerative Surgery And Potential Outcomes For Infectious And Cancer Diseases

Micro Fractured Adipose Tissue Graft (Lipogems), Regenerative Surgery And Potential Outcomes For Infectious And Cancer Diseases

One-stage cartilage repair using the autologous matrix-induced chondrogenesis combined with simultaneous use of autologous adipose tissue graft and adipose tissue mesenchymal cells technique: clinical results and magnetic resonance imaging evaluation at five-year follow-up

PurposeTo evaluate medium-term outcomes of knee cartilage defects repair by autologous matrix-induced chondrogenesis combined with simultaneous use of autologous adipose tissue graft and adipose tissue mesenchymal cells, defined as LIPO-AMIC technique.MethodsThe LIPO-AMIC technique has been used in ICRS degree III–IV knee defects. Eighteen patients have been prospectively evaluated during two and five years both clinically and by MRI.ResultsPatients showed progressive significant improvement of all scores starting early at six months, and further increased values were noted till the last follow-up at 60 months. Mean subjective pre-operative IKDC score of 36.1 significantly increased to 86.4 at 24 months and to 87.2 at 60 months. Mean pre-operative Lysholm score of 44.4 reached 93.5 at two years and 93.5 at five years. MRI examination showed early subchondral lamina regrowth and progressive maturation of repair tissue and filling of defects. The mean total MOCART score showed that a significative improvement from two year follow-up (69.1 points) to last follow-up was 81.9 points (range, 30–100 points, SD 24). Complete filling of the defect at the level of the surrounding cartilage was found in 77.8%.ConclusionsAdipose tissue can represent ideal source of MSCs since easiness of withdrawal and definite chondrogenic capacity. This study clearly demonstrated the LIPO-AMIC technique to be feasible for treatment of knee cartilage defects and to result in statistically significant progressive clinical, functional and pain improvement in all treated patients better than what reported for the AMIC standard technique, starting very early from the 6-month follow-up and maintaining the good clinical results more durably with stable results at mid-term follow-up.

Guided Superficial Enhanced Fluid Fat Injection (SEFFI) Procedures for Facial Rejuvenation: An Italian Multicenter Retrospective Case Report.

The aging process starts in the center of the face, in the periocular region and around the mouth, with a combination of volume loss, tissue descent, deepened wrinkles, and the loss of skin structure and quality. Recently, several studies have demonstrated the efficacy of therapies based on autologous adipose tissue grafting, which leverages the properties of stromal vascular fraction (SVF) and adipose-derived mesenchymal stem cells (ADSCs) to accelerate the regenerative processes of the skin. This study aims to verify the ability of guided superficial enhanced fluid fat injection (SEFFI) in the facial area to correct volume loss and skin aging, proving that this standardized procedure has a very low rate of complications. We retrospectively collected data from 2365 procedures performed in Italian centers between 2019 and 2021. Guided SEFFI was performed alone or combined with cosmetic treatments, including the use of hyaluronic acid filler, suspension threads, synthetic calcium hydroxylapatite, botulin toxin, and microneedling. guided SEFFI was used alone in more than 60% of the patients and in all facial areas. In about one-tenth of the patients, guided SEFFI was combined with a botulin toxin treatment or hyaluronic acid filling. Other procedures were used more rarely. Ecchymosis in the donor or injection sites was the most frequent adverse event but was only observed in 14.2% and 38.6% of the patients, respectively. The guided SEFFI technique is standardized and minimally invasive, leading to very few complications. It constitutes a promising antiaging medical treatment that combines effectiveness, safety, and simplicity.

Exosomes Derived from Human Adipose-Derived Stem Cells Cannot Distinctively Promote Graft Survival in Cryopreservation Fat Grafting.

Cryopreserved fat has limited clinical applications due to its rapid absorption, high degree of fibrosis, and risk of complications after grafting. Many studies have verified that Adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos) can improve fresh fat graft survival. This study assessed whether ADSC-Exos could improve the survival of cryopreserved fat grafts. Exosomes were isolated from human ADSCs were subcutaneously engrafted with adipose tissues stored under different conditions (fresh; cryopreserved for 1 month) into the backs of BALB/c nude mice (n = 24), and exosomes or PBS were administered weekly. Grafts were harvested at 1, 2, 4, and 8 weeks, and fat retention rate, histologic, and immunohistochemical analyses were conducted. At 1, 2, and 4 weeks after the transfer, cryopreserved fat grafts in groups of exosome-treated showed better fat integrity, fewer oil cysts, and reduced fibrosis. Further investigations of macrophage infiltration and neovascularization revealed that those exosomes increased the number of M2 macrophages at 2 and 4 weeks (p<0.05), but had limited impact on vascularization (p>0.05). It's important to note that no significant differences (p>0.05) were observed between the two groups in both histological and immunohistochemical evaluations at 8 weeks post-transplantation. This study suggests that ADSC-Exos could improve the survival of cryopreserved fat grafts in the short term (within 4 weeks), but the overall improvement was poor (after 8 weeks). This suggests that the utility of using ADSC-Exos to treat cryopreserved adipose tissue grafts is limited. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Clinical evidence of bio-stimulators for cervicofacial liposculpture: a systematic review

Introduction: In the liposculpture scenario, and at the cellular and molecular level, tissue engineering has numerous advantages that meet the needs of the injured tissue or organ for the regeneration process or fillings and contours. Biological microenvironments enable cell recognition and signaling cascades for neovascularization and stabilization of fat grafting. Objective: A concise systematic review was carried out on the use of potential biostimulators (cells and molecules) and the biochemical and physiological mechanisms that can contribute to the successful process of cervicofacial liposculpture, to promote neovascularization and stabilization of fat grafting or fat reduction. Methods: The systematic review rules of the PRISMA Platform were followed. The research was carried out from February to April 2022 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 96 articles were found. A total of 36 articles were fully evaluated and 34 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 11 studies at high risk of bias and 37 studies that did not meet the GRADE. The present study showed that the use of potential bio stimulators such as stromal vascular fraction cells and mesenchymal stem cells from adipose tissue, exosomes, microRNA, and PRP, as well as the molecules secreted by these cells, can contribute to the successful process of cervicofacial liposculpture, to promote neovascularization and stabilization of fat grafting or fat reduction. Furthermore, studies have shown that the use of adipose tissue plus PRP led to the presence of more pronounced inflammatory infiltrates and greater vascular reactivity, increased vascular permeability, and certain reactivity of the nervous component, noting that the addition of 20% PRP activated with calcium to adipose tissue grafts can enhance the results of regenerative and aesthetic facial surgeries.

Fatter Is Better: Boosting the Vascularization of Adipose Tissue Grafts.

Adipose tissue resorption after fat grafting is a major drawback in plastic and reconstructive surgery, which is primarily caused by the insufficient blood perfusion of the grafts in the initial phase after transplantation. To overcome this problem, several promising strategies to boost the vascularization and, thus, increase survival rates of fat grafts have been developed in preclinical studies in recent years. These include the angiogenic stimulation of the grafts by growth factors and botulinum neurotoxin A, biologically active gels, and cellular enrichment, as well as the physical and pharmacological stimulation of the transplantation site. To transfer these approaches into future clinical practice, it will be necessary to establish standardized procedures for their safe application in humans. If this succeeds, the surgical outcomes of fat grafting may be markedly improved, resulting in a significant reduction of the physical and psychological stress for the patients.

The Evaluation of Cartilage Regeneration Efficacy of Three-Dimensionally Biofabricated Human-Derived Biomaterials on Knee Osteoarthritis: A Single-Arm, Open Label Study in Egypt.

Full thickness cartilage defects in cases of knee osteoarthritis are challenging in nature and are difficult to treat. The implantation of three-dimensional (3D) biofabricated grafts into the defect site can be a promising biological one-stage solution for such lesions that can avoid different disadvantages of the alternative surgical treatment options. In this study, the short-term clinical outcome of a novel surgical technique that uses a 3D bioprinted micronized adipose tissue (MAT) graft for knee cartilage defects is assessed and the degree of incorporation of such graft types is evaluated via arthroscopic and radiological analyses. Ten patients received 3D bioprinted grafts consisting of MAT with an allogenic hyaline cartilage matrix on a mold of polycaprolactone, with or without adjunct high tibial osteotomy, and they were monitored until 12 months postoperatively. Clinical outcomes were examined with patient-reported scoring instruments that consisted of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score and the Knee Injury and Osteoarthritis Outcome Score (KOOS). The graft incorporation was assessed using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. At 12 months follow-up, cartilage tissue biopsy samples were taken from patients and underwent histopathological examination. In the results, at final follow-up, the WOMAC and KOOS scores were 22.39 ± 7.7 and 79.16 ± 5.49, respectively. All scores were significantly increased at final follow-up (p < 0.0001). MOCART scores were also improved to a mean of 82.85 ± 11.49, 12 months after operation, and we observed a complete incorporation of the grafts with the surrounding cartilage. Together, this study suggests a novel regeneration technique for the treatment of knee osteoarthritis patients, with less rejection response and better efficacy.

Fat graft survival requires metabolic reprogramming toward the glycolytic pathway

Fat grafts are widely used as natural fillers in reconstructive and cosmetic surgery. However, the mechanisms underlying fat graft survival are poorly understood. Here, we performed an unbiased transcriptomic analysis in a mouse fat graft model to determine the molecular mechanism underlying free fat graft survival. We conducted RNA-sequencing (RNA-seq) analysis in a mousefree subcutaneous fat graft model on days 3 and 7 following grafting (n = 5). High-throughput sequencing was performed on paired-end reads using NovaSeq6000. The calculated transcripts per million (TPM) values were processed for principal component analysis (PCA), unsupervised hierarchically clustered heatmap generation, and gene set enrichment analysis. PCA and heatmap data revealed global differences in the transcriptomes of the fat graft model and the non-grafted control. The top meaningful upregulated gene sets in the fat graft model were related to the epithelial-mesenchymal transition, hypoxia on day 3, and angiogenesis on day 7. Mechanistically, the glycolytic pathway was upregulated in the fat graft model at days 3 (FDR q = 0.012) and 7 (FDR q = 0.084). In subsequent experiments, pharmacological inhibition of the glycolytic pathway in mouse fat grafts with 2-deoxy-D-glucose (2-DG) significantly suppressed fat graft retention rates, both grossly and microscopically (n = 5). Free adipose tissue grafts undergo metabolic reprogramming toward the glycolytic pathway. Future studies should examine whether targeting this pathway can enhance the graft survival rate.

Fat grafts enriched with ex-vivo expanded adipose stem cells improve hyperpigmentation of face.

Facial contour deformities associated with pigmentary changes are of major concern for plastic surgeons being difficult to treat. No definite ideal treatment option is available to address simultaneously both the contour defects as well as related hyperpigmentation. The aim of the current study is to compare long-term effects of conventional adipose tissue grafting and ex-vivo expanded ASC-enrichedadipose tissue grafting for the treatment of contour deformities related pigmentary changes on the face. In this study, 80patients of contour deformities of face with hyperpigmentation were recruited after informed consent. Two techniques, that is, conventional fat grafting (C-FG)and fat grafts enriched with expanded adipose stem cells (FG-ASCs)were used to address the pigmentation. Both techniques were explained to patients and enrolled patients were divided into two groups, that is, C-FGand FG-ASCsas per patients' choice and satisfaction. Patients of the FG-ASCsgroup were treated with FG-ASCs while patients of C-FGsgroup were treated with C-FG (without expanded ASCs). Patients were followed for 12 months and improvement in face pigmentation was assessed clinically as well as measured objectively. Patients' satisfaction was also documented as highly satisfied, satisfied, and unsatisfied. This clinical trial was registered at www.clinicaltrials.gov with ID: NTC03564808. Mean age of patients was 24.42 (±4.49), 66 patients were females. Forehead was involved in 61.20% cases, cheek in 21.20% cases, chin in 11.20% cases, and nose in 6.20% cases. In GF-ASCsgroup, the integrated color density was decreased (1.08 × 106 ± 4.64 × 105 ) as compared withC-FGgroup (2.80 × 105 ± 1.69 × 105 ). Patients treated with fat grafts enriched with expanded ASCs were significantly more satisfied as compared with patients treated with C-FG only. In conclusion, ASC-enrichedautologous fat grafting is preferred option for improving the contour deformities related increased pigmentation of face skin.

New Paradigm in Diabetic Foot Ulcer Grafting Techniques Using 3D-Bioprinted Autologous Minimally Manipulated Homologous Adipose Tissue (3D-AMHAT) with Fibrin Gel Acting as a Biodegradable Scaffold

Adipose tissue is an abundant source of extracellular substances that support the tissue repair process. This pilot study was carried out to determine the efficacy of 3D-bioprinted autologous adipose tissue grafts on diabetic foot ulcers (DFUs), with fibrin gel used to stabilise the graft. This was a single-arm pilot study in a tertiary hospital that provides diabetic wound care services. A total of 10 patients with a DFU were enrolled, and the primary endpoint was complete healing within 12 weeks. The secondary endpoints were wound size reduction, time to healing, and adverse events. Seven out of ten patients showed complete healing of their DFU within 12 weeks (at 2, 4, 5, 10, and 12 weeks, respectively). The wound size reduction rate was significantly and progressively reduced over time. According to our data, autologous adipose tissue grafting using a 3D bioprinter, with the addition of fibrin gel that acts as a scaffold, promotes wound healing with high-quality skin reconstruction. Throughout this study period, no adverse events were observed.

Critical diaphyseal bone defect healing in hens by autologous free transplant of adipose tissue

Treatment of large bone defects and incurable fractures is a challenging clinical problem. A novel approaches in bone engineering is the use of adipose-derived stem cells and adipose tissue. This study aimed to analyse the impact of adipose autograft on the process of bone regeneration in a surgically created critical size defect (CSD) in the hen ulna. In this study, 30 laying hens at the age of 14 months were randomly divided into three groups: control (C, n=10), subcutaneous adipose tissue graft (SC, n=10) and abdominal adipose tissue graft (ABD, n=10). In all 30 hens, a CSD was made in the ulna. Hens from the SC and ABD groups underwent surgery to explant subcutaneous and adipose tissue graft, respectively, and those grafts were then implanted in the ulnar CSD. The first radiographic and histological analysis wer performed 3.5 weeks after surgery on four hens from the C group and five hens from the SC and ABD groups. The second analysis on the remaining 15 hens was performed after 7 weeks. Data were analysed using the Freeman-Halton extension of Fischer’s exact test at the level of statistical significance P&amp;lt;0.05. Statistically significant differences regarding the presence of bridging at 3.5 and 7 weeks after surgery were observed between the C and SC groups, and between the C and ABD groups. Formation of a callus, regardless of the time of analysis, was not observed in the C group, while it was present in the SC and ABD groups (P&amp;lt;0.05). More hens from the ABD group (3) than the SC group (1) developed a bony callus 7 weeks after surgery, though these differences were not significant. Autologous adipose tissue graft positively affected healing of the hens’ ulna at 3.5 and 7 weeks postoperatively. Abdominal adipose tissue appears to have better healing properties than subcutaneous adipose tissue.

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.

Cell-Enriched Lipotransfer (CELT) Improves Tissue Regeneration and Rejuvenation without Substantial Manipulation of the Adipose Tissue Graft.

The good availability and the large content of adult stem cells in adipose tissue has made it one of the most interesting tissues in regenerative medicine. Although lipofilling is one of the most frequent procedures in plastic surgery, the method still struggles with high absorption rates and volume losses of up to 70%. Therefore, many efforts have been made to optimize liposuction and to process the harvested tissue in order to increase fat graft retention. Because of their immunomodulatory properties, their cytokine secretory activity, and their differentiation potential, enrichment with adipose tissue-derived stem cells was identified as a promising tool to promote transplant survival. Here, we review the important parameters for lipofilling optimization. Finally, we present a new method for the enrichment of lipoaspirate with adipose tissue-derived stem cells and discuss the parameters that contribute to fat graft survival.

Regenerative and Endoscopic Treatment of Complex Recurrent Fistula in Ano: When Technology Supports Clinical Treatment

Background: Recurrent anal fistulas present a challenge to surgeons due to the high risk of post-operative incontinence caused by repeated surgery. The correct identification of the anatomy of the main and secondary fistula tracts and the individuation of abscess cavities are fundamental for correct treatment. Intraoperative endoscopic evaluation and the complete destruction of the fistula pathway can be achieved through video-assisted anal fistula treatment (VAAFT). Furthermore, the injection of human autologous Microfractured Adipose Tissue (MFAT) processed by a Lipogems® device can be used as both a bulking agent and a regenerative technique. Methods: A combined approach of VAAFT plus Microfractured Adipose Tissue Graft (MFAT) is proposed in order to treat recurrent and complex fistula in ano. Results: Three cases treated with a combination of VAAFT and MFAT grafts are described. All cases had undergone multiple interventions at the perianal level over a period ranging from 1 to 15 years. One case certainly failed due to poor patient compliance, but in the remaining two cases, the patients made a complete recovery with the disappearance of symptoms over a follow-up period of one to two years. Conclusion: The combination of video-assisted anal fistula treatment and injection of human autologous microfractured adipose tissue may be a valid, safe and feasible therapeutic option. MFAT injections are more effective in promoting tissue regeneration than simply “filling” the fistula tract and are common practice also in the treatment of Crohn’s Disease due to the immunomodulatory power of mesenchymal cells.