Expanded indications for breast-conserving surgery with oncoplastic approaches compared to conventional approaches: a single-center retrospective comparative cohort study.

Background: Oncoplastic breast-conserving surgery (OPBS) is the evolution of conventional breast-conserving surgery (CBCS); however, data from studies comparing patients who received two surgical procedures are limited. A comparison of differences in terms of the patient characteristics, tumor-nipple distance, volume of resected breast tissue, tumor volume and postoperative breast appearance between patients undergoing OPBS and CBCS was carried out in this study, enhancing the evidence base for OPBS by widening indications and improving patient satisfaction. Methods: From January 2020 to April 2022, the Breast Center of West China Hospital conducted a retrospective comparative study involving 106 patients. Preoperative characteristics of patients were recorded, and the tumor-nipple distance, the volume of resected breast tissue, tumor volume and patient-reported esthetic outcomes measured by the Harris cosmetic scale were compared between patients who underwent OPBS and CBCS. Results: Each group had a median follow-up time of 2 months, ranging from 1 week to 6 months. The tumor-nipple distance was significantly shorter in patients receiving OPBS than in those receiving CBCS (2.98±1.42 vs. 3.85±1.78 cm, P=0.006). The rate of positive margin evaluated by intraoperative frozen section biopsy was significantly lower in OPBS group than in CBCS group (2/43, 4.65% vs. 11/63, 17.46%; P=0.048). The maximum diameter of resected tissue (7.80±2.29 vs. 6.75±1.87 cm, P=0.011) and volume of resected tissue (74.20±42.77 vs. 45.52±30.99 cm3, P<0.001) were significantly larger with OPBS. The tumor size, tumor volume (either clinically measured by ultrasound or pathologically measured), tumor location, and reoperation rate due to positive margins did not differ significantly between groups. Moreover, insignificant differences existed regarding patient satisfaction between two groups (87.30% vs. 81.40%). Conclusions: The OPBS strategy allowed extensive resections and expanded indications with equivalent cosmetic satisfaction and favorable oncological safety.

Modulation of Macrophage Function by Bioactive Wound Dressings with an Emphasis on Extracellular Matrix-Based Scaffolds and Nanofibrous Composites.

Bioactive wound dressings that are capable of regulating the local wound microenvironment have attracted a very large interest in the field of regenerative medicine. Macrophages have many critical roles in normal wound healing, and the dysfunction of macrophages significantly contributes to impaired or non-healing skin wounds. Regulation of macrophage polarization towards an M2 phenotype provides a feasible strategy to enhance chronic wound healing, mainly by promoting the transition of chronic inflammation to the proliferation phase of wound healing, upregulating the level of anti-inflammatory cytokines around the wound area, and stimulating wound angiogenesis and re-epithelialization. Based on this, modulation of macrophage functions by the rational design of bioactive scaffolds has emerged as a promising way to accelerate delayed wound healing. This review outlines current strategies to regulate the response of macrophages using bioactive materials, with an emphasis on extracellular matrix-based scaffolds and nanofibrous composites.

[Renaissance of prepectoral implant-based breast reconstruction: theoretical basis and research status].

Objective: To overview the theoretical basis and research status of prepectoral implant-based breast reconstruction. Methods: The domestic and foreign researches on the application of prepectoral implant-based breast reconstruction in breast reconstruction were retrospectively analyzed. The theoretical basis, clinical advantages, and limitations of this technique were summarized and the future development trend in this field was discussed. Results: The recent advances in breast cancer oncology, the development of materials and the concept of oncology reconstruction have provided a theoretical basis for prepectoral implant-based breast reconstruction. The selection of patients and the experience of surgeons are crucial for postoperative outcomes. Ideal thickness and blood flow of flaps are the most important considerations for the selection of prepectoral implant-based breast reconstruction. However, its long-term reconstruction outcomes and clinical benefits and risks in Asian populations still need to be confirmed by more studies. Conclusion: Prepectoral implant-based breast reconstruction has a broad application prospect in breast reconstruction following mastectomy. However, the evidence is limited at present. Randomized study with long-term follow-up is urgently in need to provide sufficient evidence to evaluate the safety and reliability of prepectoral implant-based breast reconstruction.

Breast cancer cells interact with tumor-derived extracellular matrix in a molecular subtype-specific manner.

Mimicking the native microenvironment is vital for tumor engineering. Breast cancer is a highly heterogeneous disease with various molecular subtypes exhibiting distinct biological behaviors and treatment responsiveness. The heterogeneity of extracellular matrix (ECM) of breast cancer has remained largely unexplored and underestimated. The present study addressed this issue by comparing the composition, architecture, and functional roles of ECMs derived from breast cancers of two molecular subtypes, which are luminal-A breast cancer (less aggressive, ERα+)-derived ECM (LA-ECM) and triple-negative breast cancer (high aggressive, ERα-)-derived ECM (TN-ECM). Compared with normal breast tissue-derived ECMs (B-ECM), tumor-derived ECMs showed higher contents of pro-collagen I, fibronectin, and laminin, in addition with a significantly altered architecture. Transcriptome sequencing revealed that, compared with those cultured with B-ECM, MCF7 cells (an estrogen receptor (ER)α + luminal-A breast cancer cell line) cultured with LA-ECM and TN-ECM showed approximately 9.65 % and 9.04 % changes in the expression of all detected genes, respectively. The TN-ECM induced proliferation, promoted epithelial-to-mesenchymal transition, downregulated ERα expression, and reduced endocrine treatment sensitivity of MCF7. Above results have elucidated the role of phenotype-specific tumor ECM in cell phenotype maintenance, treatment sensitivity, and cancer progression, which highlighted the importance of ECM heterogeneity as well as its role in tumor microenvironment engineering and drug screening.

Methylprednisolone for idiopathic granulomatous mastitis: a prospective observational cohort study.

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign, but locally aggressive breast disease. Steroids are widely used as a breast-conserving option, however, the response rate of steroids varies in reported studies, as well as its different reported usage. This prospective observational cohort study aimed to report the outcomes of methylprednisolone for IGM treatment. Methods: From Aug 2019 to Dec 2021, the clinicopathological information of 156 IGM patients who sought treatment at West China Hospital was prospectively collected. A total of 88 patients treated with methylprednisolone were included in the study. The clinical features, treatment response, and follow-up data were analyzed. Results: The median age at diagnosis was 32 years, and 90.9% of patients were multipara. The predominant symptom at presentation was painful breast mass, with a median size of 4.7 cm. For steroid usage, an initial 20 mg methylprednisolone daily was given until disease stable. The median duration of 20 mg methylprednisolone treatment was 45 (range, 14-376) days. The median duration of whole steroid therapy was 105 (range, 28-381) days. A total of 80.7% of patients (71/88) responded well to steroid treatment. In 63 patients, steroid treatment was successfully withdrawn, and treatment was completed. With an average of 283 days follow-up (range, 0-770 days), relapse was observed in 21 (33.33%) patients. Compared with patients with residual disease as shown by physical examination (PE), those with complete clinical remission (CCR) at the end of treatment had longer relapse-free intervals. Conclusions: Steroids are the preferable breast-conserving option for IGM. Treatment with 20 mg methylprednisolone for an average of 1.5 months is usually required, and full steroid treatment might last for 3 months.

Predictive Value of Pretreatment Peripheral Neutrophil-to-Lymphocyte Ratio for Response to Neoadjuvant Chemotherapy and Breast Cancer Prognosis.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is connected with the response to neoadjuvant chemotherapy (NAC) and prognosis. In addition, residual lymph node burden after NAC is likely important for prognosis. However, most studies have focused on the predictive value of NLR for NAC pathological complete response (pCR) rate. The relationship between NLR and post-operative residual lymph node ratio (LNR), and their prognostic values remain to be determined. METHODS: We retrospectively studied 282 patients with breast cancer who underwent curative surgery after NAC from 2008 to 2018. We collected pretreatment NLR in peripheral blood, the response to NAC, and the amount of axillary lymph nodes (positive and total) from patients who received axillary lymph node dissection (ALND). We followed up all patients from 2 to 116 months, with an average of 63 months. We analyzed the predictive value of pretherapeutic NLR in peripheral blood on the response of NAC, including pCR rate and postoperative LNR. The prognostic value of NLR and LNR was also analyzed. RESULTS: A pCR was achieved in 20 (27.0%) of 74 patients with low NLR, and 34 (16.3%) of 208 with high NLR (P = 0.045). In luminal A and luminal B tumors, patients with high NLR tended to have elevated LNR (LNR>0.5; P=0.041). In Kaplan-Meier analysis, overall survival of patients with low NLR (NLR < 1.8; P = 0.033) was longer than that of patients with high NLR (NLR ≥ 1.8). Moreover, by multivariable analysis, LNR was negatively correlated with overall survival (P < 0.05) and disease-free survival (DFS) (P < 0.05). CONCLUSION: pCR rate, post-operative remaining lymph node involvement and overall survival in all patients who received NAC may be predicted by NLR. Low NLR and LNR may suggest favorable outcomes.

Hydrogel from acellular porcine adipose tissue promotes survival of adipose tissue transplantation.

Lipofilling is a popular technique for soft tissue augmentation, limited by unpredictable graft survival. This study aimed at exploring the effect of hydrogel from acellular porcine adipose tissue (HAPA) on angiogenesis and survival of adipose tissue used for lipofilling. The effect of HAPA on adipose-derived stem cells (ADSCs) proliferation, adipogenic differentiation, and vascular endothelial growth factor (VEGF) secretion were evaluated in hypoxia and normoxiain vitro. For thein vivostudy, adipose tissue with phosphate buffered saline, ADSCs, and HAPA (with or without ADSCs) were co-injected subcutaneously into nude mice. HAPA-ADSCs mixture (tissue engineering adipose tissue) was also grafted. Gross observation, volume measurement, and ultrasound observation were assessed. For histological assessment, hematoxylin and eosin, perilipin, cluster of differentiation 31 (CD31), Ki67, and transferase-mediated d-UTP nick end labelling (TUNEL) staining were performed. HAPA improved ADSCs proliferation, VEGF secretion, and adipogenic differentiation under normoxia and hypoxia conditionsin vitrostudy. For thein vivostudy, HAPA showed improved volume retention and angiogenesis, and reduced cell apoptosis when compared to ADSCs-assisted lipofilling and pure lipofilling. In conclusion, HAPA could maintain ADSCs viability and improve cell resistant to hypoxia and might be a promising biomaterial to assist lipofilling.

In situ Adipogenesis in Biomaterials Without Cell Seeds: Current Status and Perspectives.

For cosmetic and reconstructive purposes in the setting of small-volume adipose tissue damage due to aging, traumatic defects, oncological resections, and degenerative diseases, the current strategies for soft tissue replacement involve autologous fat grafts and tissue fillers with synthetic, bioactive, or tissue-engineered materials. However, they all have drawbacks such as volume shrinkage and foreign-body responses. Aiming to regenerate bioactive vascularized adipose tissue on biomaterial scaffolds, adipose tissue engineering (ATE) has emerged as a suitable substitute for soft tissue repair. The essential components of ATE include scaffolds as support, cells as raw materials for fat formation, and a tolerant local environment to allow regeneration to occur. The commonly loaded seeding cells are adipose-derived stem cells (ASCs), which are expected to induce stable and predictable adipose tissue formation. However, defects in stem cell enrichment, such as donor-site sacrifice, limit their wide application. As a promising alternative approach, cell-free bioactive scaffolds recruit endogenous cells for adipogenesis. In biomaterials without cell seeds, the key to sufficient adipogenesis relies on the recruitment of endogenous host cells and continuous induction of cell homing to scaffolds. Regeneration, rather than repair, is the fundamental dominance of an optimal mature product. To induce in situ adipogenesis, many researchers have focused on the mechanical and biochemical properties of scaffolds. In addition, efforts to regulate an angiogenic and adipogenic microenvironment in cell-free settings involve integrating growth factors or extracellular matrix (ECM) proteins onto bioactive scaffolds. Despite the theoretical feasibility and encouraging results in animal models, few of the reported cell-free biomaterials have been tested in humans, and failures of decellularized adipose tissues in adipogenesis have also been reported. In these cases, the most likely reason was the lack of supporting vasculature. This review summarizes the current status of biomaterials without cell seeds. Related mechanisms and influencing factors of in situ adipogenesis in cell-free biomaterials, dilemma in the development of biomaterials, and future perspectives are also addressed.

[Research progress of adipose-derived stem cells in skin scar prevention and treatment].

OBJECTIVE: To review the research progress of adipose-derived stem cells (ADSCs) in skin scar prevention and treatment. METHODS: The related literature was extensively reviewed and analyzed. The recent in vitroand in vivo experiments and clinical studies on the role of ADSCs in skin scar prevention and treatment, and the possible mechanisms and biomaterials to optimize the effect of ADSCs were summarized. RESULTS: As demonstrated by in vitro and in vivo experiments and clinical studies, ADSCs participate in the whole process of skin wound healing and may prevent and treat skin scars by reducing inflammation, promoting angiogenesis, or inhibiting (muscle) fibroblasts activity to reduce collagen deposition through the p38/mitogen-activated protein kinase, peroxisome proliferator activated receptor γ, transforming growth factor ß 1/Smads pathways. Moreover, bioengineered materials such as hydrogel from acellular porcine adipose tissue, porcine small-intestine submucosa, and poly (3-hydroxybutyrate-co-hydroxyvalerate) scaffold may further enhance the efficacy of ADSCs in preventing and treating skin scars. CONCLUSION: Remarkable progress has been made in the application of ADSCs in skin scar prevention and treatment. While, further studies are still needed to explore the application methods of ADSCs in the clinic.

Predictive value of tumor-infiltrating lymphocytes for response to neoadjuvant chemotherapy and breast cancer prognosis.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are predictive for the response to neoadjuvant chemotherapy (NAC) of breast cancer. However, little is known about the predictive value of TILs for axillary lymph node involvement after NAC. METHODS: We analyzed 282 breast cancer patients who were operated following NAC and curative surgery from 2008 to 2018. TILs were assessed in core needle biopsies before NAC, and the biopsies were divided into three groups: low (0%-10% immune cells in stromal tissue within the tumor), intermediate (11%-59%), and high (≥60%). The patients were followed for an average of 63 months (range, 2-116 months). We analyzed retrospectively the predictive value of TILs for the response to NAC, including pathological complete response (pCR) and axillary lymph node involvement (positive lymph node ratio (LNR; the ratio of the number of nodes involved to the total number of nodes dissected)). The prognostic values of TILs and LNR were assessed. RESULTS: A pCR was achieved in 27 of 188 patients (14.4%) in the low-TIL group, in 14 of 57 patients (24.6%) in the intermediate-TIL group, and in 13 of 37 (35.1%) in the high-TIL group (p = .007). Among patients who underwent axillary lymph node dissection after NAC, patients with high TILs had lower LNR (p = 0021) compared with the other groups. Kaplan-Meier analysis showed that overall survival (OS; p < .001) and disease-free survival (p < .001) were significantly longer for patients with low LNR (≤0.2). TILs were positively correlated with disease-free survival (p = .028), but TILs did not correlate with OS (p = .171). Moreover, by multivariable analysis, LNR independently affected disease-free survival (p < .001). CONCLUSIONS: TILs may be predictive for pCR rate, postoperative residual lymph node involvement, and disease-free survival of breast cancer patients. High TILs may suggest favorable outcomes.

Application of Carbon Nanoparticles in Tracing Lymph Nodes and Locating Tumors in Colorectal Cancer: A Concise Review.

BACKGROUND: Accurate lymph node (LN) staging has considerably prognostic and therapeutic value in patients with colorectal cancer (CRC). The purpose of this study is to evaluate the feasibility of applying carbon nanoparticles (CNPs) to track LN metastases in CRC. METHODS: Two researchers independently screened publications in PubMed, EMBASE, Cochrane and Ovid MEDLINE databases. The keywords were (carbon nanoparticles OR activated carbon nanoparticles) AND (colon cancer OR rectal cancer OR colorectal cancer). Titles and abstracts of the articles were meticulously read to rule out potential publications. Next, full texts of the ultimately obtained eligible publications were retrieved and analyzed in detail. RESULTS: The search produced 268 publications, and 140 abstracts were identified after a bibliographic review. Finally, 20 studies relevant to our subject were obtained; however, only 14 papers met our inclusion criteria and were included for final review. All studies included have compared the control group with carbon nanoparticles group (control group, defined as nontattooed group; and carbon nanoparticles group, defined as administering carbon nanoparticles during surgery) for their efficacy in intraoperative detecting and positioning. After analysis, appreciably less amount of bleeding (3/5 trials), shorter operation time (2/4 trials), and shorter time to detect lesions and dissect LNs (2/2 trials) were revealed in CNPs group compared to control group. Thirteen studies have recorded the numbers of the harvested LNs in both groups; meanwhile, CNPs group shows superiority to control group in LN retrieval as well (11/13 trials), which also could effectively aid in locating and harvesting more LNs with diameter below 5 mm. CONCLUSION: The tracing technique for CNPs is a safe and useful strategy both in localizing tumor and tracing LNs in CRC surgery. But there is still a need for more randomized controlled trials to further establish its contribution to patient survival.

[Preliminary exploration on the application of hydrogel from acellular porcine adipose tissue to assist lipofilling].

OBJECTIVE: To investigate the effect of hydrogel from acellular porcine adipose tissue (HAPA) on the survival of transplanted adipose tissue. METHODS: For in vitro study, adipose tissue and HAPA-adipose tissue complex were cultured in normoxia and hypoxia atmospheres for 24 and 72 hours. TUNEL and Perilipin immunofluorescence staining were performed to observe the effect of HAPA on apoptosis and survival of adipocities. For in vivo study, 42 healthy male nude mice (4-6 weeks old) weighing 15-18 g were randomly divided into adipose group (group A), 10%HAPA group (group B), 20%HAPA group (group C), 30%HAPA group (group D), 40%HAPA group (group E), and 50%HAPA group (group F) according to different HAPA/adipose tissue volume ratio ( n=7). For each group, 1 mL adipose tissue or HAPA-adipose tissue complex was injected subcutaneously into the dorsum of the nude mice. At 4 weeks after transplantation, 7 nude mice in each group were sacrificed and grafts were harvested, gross observation, volume measurement, ultrasound examination, and histologic staining (HE staining, CD31 and Perilipin immunofluorescence stainings) were applied. RESULTS: Hypoxia showed a tendency of promoting adipose tissue necrosis and apoptosis, while HAPA exhibited an obvious effect of inhibiting cell apoptosis in vitro study ( P<0.05). For in vivo study, grafts of all groups had intact fibrocapsule. No obvious signs of infection and necrosis were observed at 4 weeks. Volume shrinkage was observed in all groups, however, the groups A-D had significantly higher volume retention rate than groups E and F ( P<0.05). Ultrasound examination showed that there were no significant difference in the number and volume of liquify area of the grafts in each group ( P>0.05). With the increase of HAPA's volume ratio, HE staining proved an improved fat integrity while a gradually decreased vacuoles and fibrosis. CD31 immunohistochemical staining showed that the number of neo-vascularisation in groups E and F were significantly higher than those in groups A-D ( P<0.05). Perilipin immunofluorescence staining showed that with the increase of HAPA volume ratio, the number of living adipocytes increased gradually, and more new adipocytes could be seen in the field of vision. CONCLUSION: As the volume ratio of HAPA gradually increased, the survival of transplanted adipose tissue also increased, but the volume retention rate decreased gradually. 30%HAPA was considered the relative optimal volume ratio for its superior adipose tissue survival and volume retation rate.

Predicting Survival Benefit of Sparing Sentinel Lymph Node Biopsy in Low-Risk Elderly Patients With Early Breast Cancer: A Population-Based Analysis.

Objective: The application of sentinel lymph node biopsy (SLNB) in elderly patients with early breast cancer remains somewhat controversial. This study aimed to establish individualized nomograms to predict survival outcomes of elderly patients with and without SLNB and find out which patients could avoid SLNB. Methods: A total of 39,962 ≥70-year-old patients diagnosed with T1-T2 breast cancer in 2010-2015 were included from the Surveillance, Epidemiology, and End Results (SEER) program and were divided into the training set (n = 29,971) and the validation set (n = 9,991). Axillary surgery was not specified in the SEER database, and we defined removing one to five lymph nodes as SLNB. Survival analysis was performed using the Kaplan-Meier plot and log-rank test. Multivariate Cox analysis was utilized to identify risk factors for overall survival (OS) and breast-cancer-specific survival (BCSS). Nomograms and a risk stratification model were constructed. Results: In the training set, patients with SLNB had better OS (adjusted HR 0.57, P < 0.001) and BCSS (adjusted HR 0.55, P < 0.001) than patients without SLNB. Multivariate COX analysis identified age, marital status, grade, subtype, T stage, and radiation as independent risk factors for OS and BCSS in both SLNB and non-SLNB groups (all P < 0.05). They were subsequently incorporated to establish nomograms to predict 3- and 5-year OS and BCSS for patients with or without SLNB. The concordance index ranged from 0.687 to 0.820, and calibration curves in the internal set and external set all demonstrated sufficient accuracies and good predictive capabilities. Further, we generated a risk stratification model which indicated that SLNB improved OS and BCSS in high-risk group (OS: HR 0.49, P < 0.001; BCSS: HR 0.54, P < 0.001), but not in the low-risk group (all P > 0.05). Conclusion: Well-validated nomograms and a risk stratification model were constructed to evaluate survival benefit from SLNB in elderly patients with early-stage breast cancer. SLNB was important for patients in the high-risk group but could be omitted in the low-risk group without sacrificing survival. This study could assist clinicians and elderly patients to weigh the risk-benefit of SLNB and make individualized decisions. We look forward to more powerful evidence from prospective trials.

Adjuvant chemotherapy-associated lipid changes in breast cancer patients: A real-word retrospective analysis.

Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy regimens remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare the side effects of different chemotherapy regimens on serum lipid.We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy regimens:The levels of triglycerides (TG), total cholesterols (TC), and low-density lipoprotein (LDL-C) were significantly elevated in patients who received chemotherapy regimens above (P < .001). With respect to different chemotherapy regimens, FEC had less side effects on lipid profiles (TG (P = .006), high-density lipoprotein (HDL-C) (P < .001), and LDL-C (P < .001)) than TC regimen and AC-T and EC-T regimen. Also, the incidence of newly diagnosed dyslipidemia after chemotherapy was lower in FEC group than TC group and AC-T and EC-T group (P < .001). Additionally, the magnitude of the alterations in lipid profiles (TG, TC, HDL-C, and LDL-C) was greater in premenopausal patients than that of the postmenopausal patients (P = .004; P < .001; P = .002; P = .003, respectively). Moreover, after adjusting for multiple baseline covariates, anthracycline-plus-taxane-based regimens (AC-T and EC-T) were still statistically associated with a high level of TG (P = .004) and a low level of HDL-C (P = .033) after chemotherapy compared with FEC regimen. Also, body mass index (BMI) > 24 was associated with abnormal lipid profiles (TG, TC, HDL-C, LDL-C) post-chemotherapy compared with BMI ≤ 24 (P < .001; P = .036; P = .012; P = .048, respectively).BC patients receiving chemotherapy may have elevated lipid profiles, and anthracycline-based regimen had less side effects on lipid profiles compared with regimens containing taxane. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and dyslipidemia prevention and corresponding interventions are indispensable during the whole chemotherapy period.

[Wound-induced hair follicle neogenesis: a new perspective on hair follicles regeneration in adult mammals].

OBJECTIVE: To explore the research progress of the cell sources and related signaling pathways of the wound-induced hair follicle neogenesis (WIHN) in recent years. METHODS: The literature related to WIHN in recent years was reviewed, and the cell sources and molecular mechanism were summarized and discussed. RESULTS: Current research shows that WIHN is a rare regeneration phenomenon in the skin of adult mammals, with multiple cell origins, both hair follicle stem cells and epithelial stem cells around the wound. Its molecular mechanism is complicated, which is regulated by many signaling pathways. Besides, the process is closely related to the immune response, the immunocytes and their related cytokines provide suitable conditions for this process. CONCLUSION: There are still many unsolved problems on the cellular origins and molecular mechanisms of the WIHN. Further study on the mechanisms will enhance the understanding of adult mammals' hair follicle regeneration and may provide new strategy for functional healing of the human skin.

Hydrogel from Acellular Porcine Adipose Tissue Accelerates Wound Healing by Inducing Intradermal Adipocyte Regeneration.

As an important component of the skin, intradermal adipocytes are closely associated with skin homeostasis and wound healing. Although studies have focused on the role of fibroblasts, keratinocytes, and inflammatory cells in wound healing, the role of adipocytes has not been fully investigated. Here, we verified whether the induction of adipocyte regeneration in a wound bed can effectively promote wound healing, finding that the hydrogel from acellular porcine adipose tissue in combination with adipose-derived stem cells can induce in situ adipogenesis in the wound microenvironment. The newly regenerated adipocytes enhanced fibroblast migration, accelerated wound closing, and enhanced wound epithelialization. More importantly, newly formed intact skin structure was observed after treating the wound with adipose-derived stem cell-loaded hydrogel from acellular porcine adipose tissue. These results show that hydrogel from acellular porcine adipose tissue might substantially improve re-epithelialization, angiogenesis, and skin-appendage regeneration, making it a promising therapeutic biomaterial for skin wound healing.

[Effects of adipose-derived stem cells and endothelial cells on survival and neovascularization of fat tissue transplants].

Objective: To investigate the effects of adipose-derived stem cells (ADSCs) and endothelial cells (ECs) on the survival and neovascularization of fat tissue transplants. Methods: The ADSCs were isolated by collagenase digestion from the adipose tissues voluntarily donated by the patients undergoing mastectomy, and subcultured. The passage 3 ADSCs were used for subsequent experiments. The residual fat tissues were used to prepare fat particles (FPs). The human umbilical vein endothelial cells (HUVECs) were used as ECs for subsequent experiments. Eighty healthy male nude mice, aged 4-6 weeks, were randomly divided into 4 groups ( n=20). The mice were received subcutaneous injection at the dorsum of 1 mL FPs+0.3 mL normal saline (NS) in control group, 1 mL FPs+2×10 6 ECs+0.3 mL NS in ECs group, 1 mL FPs+2×10 6 ADSCs+0.3 mL NS in ADSCs group, and 1 mL FPs+1×10 6 ECs+1×10 6 ADSCs+0.3 NS in ADSCs+ECs group. General observations of the injection sites were performed, and the survival of the mice was recorded. At 2, 4, 8, and 12 weeks after injection, grafted fat tissues were firstly assessed by ultrasonography, then they were collected for volume measurement (water displacement method) and histology observation (HE staining and immunofluorescence staining). Results: All mice survived until the end of experiment. At each time point, no significant difference was noted between groups in ultrasonography assay. There was no significant blood flow signal in the grafted fat tissues, or cysts, calcification, solid occupying in recipient area. Generally, the volume of grafted fat tissues decreased with time in all groups. Specifically, the volumes of grafted fat tissues were larger in ADSCs group and ADSCs+ECs group than that in control group and ECs group ( P<0.05) at each time point, and in ADSCs group than in ADSCs+ECs group ( P<0.05) at 8 and 12 weeks. HE staining showed that all groups had similar tendencies in general histology changes, and remodeling in ADSCs group was the fastest than in the other groups. By immunofluorescence staining for neovascularization, the new vessels in all groups were increasing with time. The vessel densities were higher in ECs group, ADSCs group, and ADSCs+ECs group than in control group ( P<0.05) at each time point, in ADSCs group than in ECs group and ADSCs+ECs group ( P<0.05) at 4 weeks, in ADSCs group and ADSCs+ECs group than in ECs group ( P<0.05) at 8 and 12 weeks. Conclusion: ADSCs can significantly increase the survival of transplanted fat tissue, which may be related to promoting the neovascularization.

Evaluating the angiogenic potential of a novel temperature-sensitive gel scaffold derived from porcine skeletal muscle tissue.

Our previous study fabricated decellularized porcine muscle tissues (DPMTs) and demonstrated that DPMTs with few cell residues possess highly preserved protein components and good biocompatibility. In the physical state, skeletal muscle equips an abundant vascular network due to the vast demand of energy from aerobic metabolism. Vascular bioactive factors which are rich in skeletal muscle tissues may contribute to the angiogenic effect of DPMTs. However, implanting DPMTs in vivo in a less invasive way is unfeasible. Hence, the purpose of this study was to fabricate DPMTs into hydrogel and investigate the effects of DPMT gel on promoting neovessel formation in vitro and in vivo. The results demonstrated that the surface topographies of the DPMT gel were looser and more homogeneous than the DPMTs. The rates of retained VEGF, bFGF, and PDGF-BB in DPMT gel were almost half of the corresponding content in fresh skeletal muscle tissues. Human umbilical endothelial cells displayed better proliferation ability and enhanced the formation of neovascular loops when seeded on DPMT gel compared to small intestinal submucosa gels at the same concentration of 2% (W/V). Furthermore, the increased neovessel formation was detected after subcutaneous injection of DPMT gel. Taken together, these findings suggested that DPMT gel may possess the potential of promoting neovascular formation.

The Effects of Platelet-Rich Plasma and Adipose-Derived Stem Cells on Neovascularization and Fat Graft Survival.

BACKGROUND: Adipose-derived stem cell (ADSCs)-assisted and platelet-rich plasma (PRP)-assisted lipofilling aim to enhance angiogenesis and cell proliferation and are promising techniques for lipofilling. This study aimed to compare the outcomes of ADSCs-assisted and PRP-assisted lipofilling. METHODS: Adipose tissue and human venous blood were obtained from women with early breast cancer. Human ADSCs were isolated and amplified in vitro. PRP was extracted through double centrifugation. The effect of PRP on ADSCs proliferation was evaluated. In the in vivo study, 1 ml of adipose tissue with saline (control group), PRP (PRP group), or ADSCs (ADSCs group) was injected subcutaneously into the dorsum of nude mice. At 2, 4, 8, and 12 weeks after injection, tissues were assessed for volume retention and ultrasound abnormality. For histological assessment, hematoxylin and eosin staining were performed. RESULTS: Cytokines in PRP and blood were comparable. Regarding the in vitro assay, PRP significantly improved ADSCs proliferation, and the effect was dose-dependent. Concerning the in vivo study, for each time point, ADSCs-assisted lipofilling showed superior volume maintenance. Similarly, the PRP group showed improved angiogenesis and fat survival, as compared with the control group. The angiogenic effect of PRP was inferior to that of ADSCs at most time points. No significant difference was observed at 12 weeks after lipofilling. Complication rates were comparable between the PRP group and ADSCs group. CONCLUSIONS: PRP-assisted and ADSCs-assisted lipofilling can significantly improve the cosmetic results of grafted fat. PRP-assisted lipofilling, which is considered convenient and clinically available, is a promising technique to improve neovascularization and fat survival. NO LEVEL ASSIGNED: 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 value of positive lymph nodes ratio combined with negative lymph node count in prediction of breast cancer survival.

BACKGROUND: Positive lymph node ratio (LNR), defined as ratio of positive lymph nodes to all lymph nodes removed, is a powerful prognostic factor in invasive breast cancer. Here we focused on the impact of negative lymph node (NLN) count on the prediction of value of LNR in breast cancer survival. METHODS: Of 929 invasive breast cancer patients were enrolled in our retrospective study. We use Kaplan-Meier to calculate the 5-year overall survival (OS) according to different clinicopathologic parameters. The prediction value of NLN count and LNR in OS was examined. RESULTS: The optimal cutoff of NLN count was designated as 9. Five-year OS was 77.0% and 95.0% in patients with NLN of 0-9 and ≥10, respectively (P<0.001). Among 204 patients who had 0-9 NLN, 25 patients with LNR 0-20.0% had 5-year OS of 95.7%, 104 patients with LNR 20.1-65.0% had 5-year OS of 83.4%, and 75 patients with LNR 65.1-100.0% had 5-year OS of 61.7% (P<0.001); Among 725 patients who had NLN ≥10, 650 patients with LNR 0-20.0% had 5-year OS of 96.1%, 68 patients with LNR 20.1-65.0% had 5-year OS of 86.8%, and 7 patients with LNR 65.1-100% had 5-year OS of 71.4% (P<0.001). CONCLUSIONS: High NLN count is associated with improved survival in invasive breast cancer patients. Combining NLN count with LNR could be considered as an alternative to LNR alone in prediction of postoperative breast cancer survival.