BACKGROUND: Autologous fat grafting (AFG) has emerged as a highly sought-after plastic surgery procedure, although its success has been hampered by the uncertain fat survival rate. Current evidence suggests that adipose-derived stem cells (ADSCs) may contribute to fat retention in AFG. In previous studies, it was confirmed that thymosin beta 4 (Tβ4) could enhance fat survival in vivo, although the precise mechanism remains unclear.
METHODS: ADSCs were isolated from patients undergoing liposuction and their proliferation, apoptosis, anti-apoptosis, and migration were analyzed under Tβ4 stimulation using cell counting kit-8, flow cytometry, wound healing assay, and real-time quantitative PCR. The mRNA levels of genes relating to angiogenesis and Hippo signaling were also determined.
RESULTS: Tβ4 at 100 ng/mL (p-value = 0.0171) and 1000 ng/mL (p-value = 0.0054) significantly increased ADSC proliferation from day 1 compared to the control group (0 ng/mL). In addition, the mRNA levels of proliferation-associated genes were elevated in the Tβ4 group. Furthermore, Tβ4 enhanced the anti-apoptotic ability of ADSCs when stimulated with Tβ4 and an apoptotic induction reagent (0 ng/mL vs. 1000 ng/mL, p-value = 0.011). Crucially, the mRNA expression levels of angiogenesis-related genes and critical genes in the Hippo pathway were affected by Tβ4 in ADSCs.
CONCLUSIONS: Tβ4 enhances adipose viability in AFG via facilitating ADSC proliferation and reducing apoptosis, and acts as a crucial positive regulator of ADSC-associated angiogenesis. Additionally, Tβ4 could be accountable for the phenotypic adjustment of ADSCs by regulating the Hippo pathway.
METHODS: 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 .

Autologous fat grafting is the gold standard for treatment in patients with soft-tissue defects. However, the technique has a major limitation of unpredictable fat resorption due to insufficient blood supply in the initial phase after transplantation. To overcome this problem, we investigated the capability of a medical-grade poly L-lactide-co-poly ε-caprolactone (PLCL) scaffold to support adipose tissue and vascular regeneration. Deploying FDM 3D-printing, we produced a bioresorbable porous scaffold with interconnected pore networks to facilitate nutrient and oxygen diffusion. The compressive modulus of printed scaffold mimicked the mechanical properties of native adipose tissue. In vitro assays demonstrated that PLCL scaffolds or their degradation products supported differentiation of preadipocytes into viable mature adipocytes under appropriate induction. Interestingly, the chorioallantoic membrane assay revealed vascular invasion inside the porous scaffold, which represented a guiding structure for ingrowing blood vessels. Then, lipoaspirate-seeded scaffolds were transplanted subcutaneously into the dorsal region of immunocompetent rats (n = 16) for 1 or 2 months. The volume of adipose tissue was maintained inside the scaffold over time. Histomorphometric evaluation discovered small- and normal-sized perilipin+ adipocytes (no hypertrophy) classically organized into lobular structures inside the scaffold. Adipose tissue was surrounded by discrete layers of fibrous connective tissue associated with CD68+ macrophage patches around the scaffold filaments. Adipocyte viability, assessed via TUNEL staining, was sustained by the presence of a high number of CD31-positive vessels inside the scaffold, confirming the CAM results. Overall, our study provides proof that 3D-printed PLCL scaffolds can be used to improve fat graft volume preservation and vascularization, paving the way for new therapeutic options for soft-tissue defects.

One in seven women will develop breast cancer, making it the most common female cancer worldwide. Consequently, breast cancer-related treatment, including breast reconstruction, impacts societal costs. Autologous fat transfer (AFT) is a relatively new breast reconstruction technique; however, several surgeries are necessary. This study investigates if AFT with pre-expansion is more cost-effective than implant-based reconstruction (IBR).
Seven centers assigned patients randomly from 2015 to 2021 to evaluate costs and EQ-5D-5L quality-adjusted life years (QALY) of AFT vs. IBR at 12 months postoperative. Costs were calculated, including direct costs related to treatment and PROductivity and DISease Questionnaire, to estimate productivity loss (indirect costs). Sensitivity analyses were performed for 10- and 30 years to estimate costs for patients replacing or explanting their breast implants over time.
A total of 152 women, of which 91 received AFT (mean age 49.3) and 80 IBR (mean age 49.1). The mean EQ-5D-5L QALY in the AFT group was 0.83, compared with the IBR group of 0.79. Total costs for AFT at 12 months postoperative were higher than IBR (incremental cost: €6763.59). Sensitivity analyses for 10- and 30-year scenarios showed mean incremental costs of respectively €2586.56 and €680.22.
Mean EQ-5D-5L QALY and costs were higher for AFT over the first year after reconstruction. However, these costs were low; therefore, AFT was estimated to be more cost-effective over the 10- and 30-year period since no additional surgeries are necessary for this group. Larger cohorts are required to confirm AFT is more cost-effective in the long term.

Postherpetic neuralgia (PHN) is one of the most common complications of Herpes zoster (HZ), yet the mechanism and the treatment for PHN remains elusive. We first performed this feasibility study to verify the safety and efficiency of autologous fat grafting into the paravertebral space in early HZ to prevent PHN.
Patients suffering from HZ with a rash in chest, back, or abdomen were arranged for autologous fat grafting to the paravertebral space. The primary endpoint was the incidence of PHN, which was defined as persistence pain in the affected dermal area in 12 weeks after fat grafting. Secondary endpoints including patient-reported changes in pain intensity, assessed pain threshold and the quality of life during follow-ups.
Eight patients accept the intervention and completed all follow-ups. Most patients report immediate pain relief after injection, one patient has a mild to moderate dizzy symptom after injection. No other short- or long-term adverse events occurred. For primary outcome, all patients have a timely reduced pain intensity, with no PHN events occurred, as all patients report pain intensity ≤3 in the VAS scale in 3 months after treatment. For electrical pain threshold, we identify that fat grafting differentially increases sensation and pain threshold in HZ area and healthy skin of patients. Besides, our results indicate significant improvement in patients\' life quality decrease in analgesic consumption.
Autologous fat transplantation to the paravertebral space is a safe and feasible technique in preventing PHN from HZ in a rash. Further randomized controlled trial to investigate the actual long-term benefice of autologous fat grafting to the paravertebral space in preventing PHN is needed.
ChiCTR, (ChiCTR1900025416); registered August 26, 2019.

UNASSIGNED: Cell-assisted lipotransfer (CAL), a modified adipose-derived stromal/stem cells (ADSCs)-based approach for autologous fat grafting that is an ideal option for soft tissue augmentation, has many shortcomings in terms of retention and adverse effects. The objective of our study was to improve the treatment efficacy of CAL by adding fibroblasts.
UNASSIGNED: ADSCs and fibroblasts were isolated from human adipose and dermal tissues, with fibroblasts identified by immunofluorescence and ADSCs identified by the multilineage differentiation method. We performed cell proliferation, apoptosis, migration, adipogenic, and hemangioendothelial differentiation experiments, qPCR and Western blotting analysis in co-cultures of fibroblasts and ADSCs. Subsequently, we conducted animal experiments with BALB/c nude mice. Masson\'s staining, immunofluorescence staining and ultrasound were used to analyze the occurrence of adverse reactions of the grafted fat, and CT and three-dimensional reconstruction were used to accurately evaluate the volume of the grafted fat.
UNASSIGNED: We found that the co-culture of fibroblasts and ADSCs promoted their mutual proliferation, adipogenic differentiation, hemangioendothelial differentiation and proliferation and migration of HUVECs. Fibroblasts inhibit the apoptosis of ADSCs. Moreover, in animal experiments, the autografted adipose group combined with ADSCs and fibroblasts had the least occurrence of oily cysts, and fat had the best form of survival.
UNASSIGNED: We enhanced adipocyte regeneration and angiogenesis in ADSCs and fibroblast cells after adding fibroblasts to conventional CAL autologous fat grafts. In turn, the volume retention rate of the grafted fat is improved, and the adverse reactions are reduced.

Autologous fat grafting for correcting soft-tissue defects in cosmetic and reconstructive procedures has grown in popularity. Fat processing is implicated as a variable affecting quality, viability, and subsequent graft retention. This study aimed to identify a better fat processing technique for optimal outcomes.
Fresh human aspirated fat was processed with cotton gauze rolling or centrifugation and named rolled fat (RF) and centrifuged fat (CF), respectively. Processed fat grafts were analyzed in vitro to determine yield, stromal vascular fraction (SVF) content, and viability. Then, RF and CF were transplanted subcutaneously to different flanks of every nude mouse. Fat samples were weighed to evaluate the volume retention 3 months post-transplantation. Tissue structure, densities of vessels, and CD68-positive macrophages were examined by histological staining.
The compression rate of lipoaspirate by cotton gauze rolling was 25%, which was more effective than the rate of 50% by centrifugation. The numbers of SVF cells per gram of RF and CF were (1.02 ± 0.14) ×106 and (0.65 ± 0.26)×106, respectively (P < 0.05). Long-term graft retention was significantly higher in the RF group than in the CF group. Histological analysis of all implants revealed intact adipose tissue and equivalent vascularity. The number of CD68-positive macrophages in the RF group was much less than in the CF group on day 7.
The results of this animal experiment showed that, compared with centrifugation, processing with cotton gauze rolling produces more condensed fat, higher SVF content, and decreased inflammatory response, thereby improving long-term volume retention. Further explorations are required to verify the superiority of cotton gauze rolling in clinical settings.

UNASSIGNED: Microcirculation plays a vital role in scleroderma physiopathology and the mechanism of fat survival.
UNASSIGNED: This study aims to assess the blood perfusion change after fat grafting and evaluate the relationship between blood perfusion and fat graft retention in patients with localized scleroderma (LS).
UNASSIGNED: A pilot study was conducted in patients with LS receiving autologous fat grafting (AFG). Fat graft retention measured by magnetic resonance imaging (MRI) analysis and blood flow perfusion measured by laser speckle contrast imaging 6 months postoperatively were noted. PUMC Localized Scleroderma Facial Aesthetic Index was used to assess the improvement of facial aesthetic impairment.
UNASSIGNED: The fat retention at the 6-month follow-up was 34.56 ± 11.89 percent. At the 6th month of follow-up, the relative blood perfusion at the lesion area was 115.08 ± 14.39 PU, significantly higher than 100.42 ± 10.62 PU at the pre-operation (p = 0.010). The blood perfusion at follow-up increased by an average of 1.15 ± 0.14 times before the operation. No association between the increase in the blood flow perfusions and fat graft retention was found (r = -0.082, p = 0.811).
UNASSIGNED: Local blood perfusion in the lesion area relatively increased after AFG, but no direct relationship was found between fat retention and increased blood supply.

UNASSIGNED: Autologous fat grafting (AFG) is a technique that can improve the appearance of breasts in surgical patients. There are currently few studies on breast-conserving surgery (BCS) combined with immediate AFG, although we believe that it could achieve satisfactory effects. Therefore, the purpose of this study is to observe the effects of BCS combined with immediate AFG on oncologic safety, satisfaction and psychology of breast cancer patients.
UNASSIGNED: We retrospectively collected the data of 85 breast cancer patients from February 2018 to October 2018. After screening, 40 patients in AFG group (AG, BCS combined with immediate AFG) and 40 patients in control group (CG, BCS alone) were finally included in the study. The primary outcomes were the survival, tumor recurrence and metastasis, and BREAST-Q score of patients. The secondary outcomes were short and long-term complications, degree of depression and anxiety of patients.
UNASSIGNED: A total of 80 patients were included in the analysis. There was no significant difference in the clinicopathological data between the two groups (P>0.05). The average follow-up time of the two groups was 40.58±2.630 and 40.28±2.679 months. In the analysis of oncologic safety, no patients died in AG and 1 patient died in CG. In addition, there was no significant difference between the two groups in terms of the overall recurrence rate and the distribution of recurrence types (P>0.05). As for satisfaction, the BREAST-Q score of AG was significantly higher than that of CG (57.85±4.833 vs 51.93±5.045, P<0.001). In the secondary outcomes, there was no short-term complication specified in the study; in the long-term complications, the incidence of calcification in AG was not significantly higher than that in CG (P=0.065). In the analysis of depression and anxiety, there was no significant difference between the two groups (P>0.05).
UNASSIGNED: BCS combined with immediate AFG can significantly improve patients\' satisfaction without increasing the risk of death and tumor recurrence. However, it does not seem to play a role in improving the conditions of depression and anxiety.

Soft tissue expansion is a common technique for the regeneration of extra skin to repair skin defects. However, some warning signs like skin thinning and telangiectasia are often found during the expansion process, which indicates the skin flaps cannot be further expanded. These signs may result in the suspension of expansion or ultimately jeopardize the final outcome. Fat grafting is used to treat these potential complications and enable the continuation of the expansion procedure in some cases. In this study, we aimed to investigate the efficiency and safety of fat grafting in this process.
The study was conducted on patients from January 2012 to December 2017 with warning signs of expansion treated with fat grafting (treatment group) or pause expansion (control group). Follow-up data, such as expansion status, dermal thickness, telangiectasia, skin texture using volume assessment, B-mode ultrasound, and semiquantitative scoring, were collected.
A total of 67 expanded skin regions with warning signs were enrolled. The expansion fold increased 2.14-fold at 12 weeks after treatment compared with 0.74-fold in control (P=0.02). The semiquantitative score was significant improved at 4 weeks (9.03 ± 0.73 vs. 7.45 ± 0.55; p=0.033). Meanwhile, the skin thickness in the experimental group did not show decreasing trend even in the continued expansion process.
Autologous fat grafting represents an effective and safe method to rescue expanded skin from limited skin regeneration. This technique also represents a valuable tool to increase the chances for further expansion.

BACKGROUND: Autologous fat grafting (AFG), defined as the re-implant to the breast of fat tissue from different body areas, has been firstly applied to esthetic plastic surgery and then has moved to reconstructive surgery, mainly used for scar correction and opposite breast altering. Nevertheless, due to the potentially unsafe stem-like properties of adipocytes at the tumoral bed level, no clear evidence of the procedure\'s oncological safety has been clearly documented at present.
METHODS: We retrospectively collected data of early breast cancer (BC) patients from 17 Italian Breast Units and assessed differences in terms of locoregional recurrence rate (LRR) and locoregional recurrence-free survival (LRFS) between patients who underwent AFG and patients who did not. Differences were analyzed in the entire cohort of invasive tumors and in different subgroups, according to prognostic biological subtypes.
RESULTS: With a median follow-up time of 60 months, LRR was 5.3% (n = 71) in the matched population, 3.9% (n = 18) in the AFG group, and 6.1% (n = 53) in the non-AFG group, suggesting non-inferiority of AFG (p = 0.084). Building Kaplan-Meier curves confirmed non-inferiority of the AFG procedure for LRFS (aHR 0.73, 95% CI 0.41-1.30, p = 0.291). The same effect, in terms of LRFS, was also documented among different biological subtypes (luminal-like group, aHR 0.76, 95% CI 0.34-1.68, p = 0.493; HER2 enriched-like, aHR 0.89, 95% CI 0.19-4.22, p = 0.882; and TNBC, aHR 0.61, 95% CI 0.12-2.98, p = 0.543).
CONCLUSIONS: Our study confirms in a very large, multicenter cohort of early BC patients that, aside the well-known benefits on the esthetic result, AFG do not interfere negatively with cancer prognosis.