Manufacture and evaluation of nano-silver-poly-DL-lactide-co-caprolactone-small intestinal submucosa biological mesh in abdominal wall reconstruction.

Background: Inguinal hernia repair is a routine surgical procedure and many methods are being applied to improve the operation. In this study, an abdominal wall defect model was established in New Zealand rabbits. The safety and efficacy of the test product was evaluated by observing the physiological state and clinical manifestations and conducting anatomical observations in the rabbits after use of the nano-silver-poly-DL-lactide-co-caprolactone-small intestinal submucosa (NS-PLCL-SIS) mesh. Methods: A total of 18 New Zealand rabbits were randomly divided into a test group and a blank group. Routine blood and serum biochemical tests, and anatomical observations were conducted on postoperative day 30 (D30), day 60 (D60), and day 90 (D90). During the study period, all animals underwent clinical observation, and the obtained data were counted. Results: The results showed that the NS-PLCL-SIS mesh was degraded within 90 days, and there was no abnormal reaction and no animal death during the test. There was no significant difference in the changes of animal body weight at each time point. There was no infectious inflammatory reaction in the wound at the study site, and the ocular wound healed well 7 days after the operation. Conclusions: Under the conditions of this experiment, the NS-PLCL-SIS mesh had good performance in the repair of abdominal wall defect in New Zealand rabbits and is clinically safe for veterinarians.

Predicting the recurrence-free survival of phyllodes tumor of the breast: a nomogram based on clinicopathology features, treatment, and surgical margin.

Background: Grading based on histopathologic indicators cannot accurately assess the prognosis of phyllodes tumor (PT) of the breast. This article aimed to investigate the correlation between PT prognosis and clinicopathological features, treatment, and surgical margin. Methods: The clinicopathological data of patients with pathologically confirmed PT at our institution were retrospectively collected. Univariate and multivariate Cox proportional risk models were employed to test the effects of different variables on the prognosis of PT. A nomogram to predict the 1-, 3-, 5-, and 10-year recurrence-free survival (RFS) of PT was proposed, and its discriminative ability and calibration were tested using the concordance index (C-index), area under the curve (AUC), and calibration plots. All statistical analyses were performed using R. Results: A total of 342 PT patients were included, including 242 benign (70.8%), 75 borderline (21.9%) and 25 malignant (7.3%) cases. The median follow-up period was 64.5 months (range, 3-179 months), 66 PT patients had local recurrence (LR), and four patients had distant metastasis. The 1-, 3-, 5-, and 10-year RFS of the PT patients were 90.8%, 81.8%, 78%, and 76.7%, respectively. Age, fibroadenoma (FA) surgery history, treatment, mitotic activity, and surgical margin were selected as the independent factors for PT prognosis. The nomogram showed good discriminative ability and calibration, as indicated by the C-index [0.78, 95% confidence interval (CI): 0.75-0.11]. Conclusions: Independent predictors related to PT prognosis were selected to establish a nomogram for predicting the RFS of PT. This nomogram was able to objectively stratify PT patients into prognostic groups and performed well in the internal validation.

Clinicopathological Characteristics and Prognostic Profiles of Breast Carcinoma with Neuroendocrine Features.

BACKGROUND: Breast carcinoma with neuroendocrine features includes neuroendocrine neoplasm of the breast and invasive breast cancer with neuroendocrine differentiation. This study aimed to investigate the clinicopathological features and prognosis of this disease according to the fifth edition of the World Health Organization classification of breast tumors. MATERIALS AND METHODS: A total of 87 patients with breast carcinoma with neuroendocrine features treated in the First Medical Center, Chinese PLA General Hospital from January 2001 to January 2022 were retrospectively enrolled in this study. RESULTS: More than half of the patients were postmenopausal patients, especially those with neuroendocrine neoplasm (62.96%). There were more patients with human epidermal growth factor receptor 2 negative and hormone receptor positive tumors, and most of them were Luminal B type (71.26%). The multivariate analysis showed that diabetes and stage IV disease were related to the progression-free survival of breast carcinoma with neuroendocrine features patients (p = 0.004 and p < 0.001, respectively). CONCLUSION: Breast carcinoma with neuroendocrine features tended to be human epidermal growth factor receptor 2 negative and hormone receptor positive tumors, most of them were Luminal B type, and the related factors of progression-free survival were diabetes and stage IV disease.

Differences of Clinicopathological Features between Metaplastic Breast Carcinoma and Nonspecific Invasive Breast Carcinoma and Prognostic Profile of Metaplastic Breast Carcinoma.

Introduction: Metaplastic breast carcinoma is a rare special type of breast cancer, which has distinguished clinical characteristics. We aimed to evaluate the clinicopathological features of metaplastic breast carcinoma compared with nonspecific invasive breast carcinoma and study the prognosis of metaplastic breast carcinoma. Methods: We reviewed metaplastic breast carcinoma cases (n = 37) from January 2000 to December 2021 and nonspecific invasive breast carcinoma cases (n = 433) from January 2019 to December 2020 extracted from our institution retrospectively. The following variables were recorded, including the patients' general information, complications, T stage, expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, molecular subtyping, lymph node status, skin or chest wall involvement, vessel carcinoma embolus, therapy modality (surgical treatments, chemotherapy, and radiotherapy), and survival. Results: Patients with metaplastic breast carcinoma had more advanced disease than patients with nonspecific invasive breast carcinoma (T stage: P=0.0011). A greater proportion of metaplastic breast carcinoma presented with triple-negative breast cancer than nonspecific invasive breast carcinoma (79.41% vs. 12.47%, P ≤ 0.001). Our study showed that the skin or chest wall invasion was more frequent in metaplastic breast carcinoma patients (11.76% vs. 1.62%, P=0.005). The 5-year survival rate for metaplastic breast carcinoma patients was 57.66% (95% CI: 0.3195∼0.7667). No local recurrence was observed while distant metastasis occurred in 33.33% of patients with metaplastic breast carcinoma. Death due to disease occurred in 24.24% of patients with metaplastic breast carcinoma. Conclusion: The majority of metaplastic breast carcinoma patients had more advanced disease and triple-negative disease than nonspecific invasive breast carcinoma patients. Also, metaplastic breast carcinoma patients had frequent skin or chest wall invasion and a high rate of distant metastasis and mortality.

Nontherapeutic Risk Factors of Different Grouped Stage IIIC Breast Cancer Patients' Mortality: A Study of the US Surveillance, Epidemiology, and End Results Database.

Objectives: Stage IIIC breast cancer, as a local advanced breast cancer, has a poor prognosis compared with that of early breast cancer. We further investigated the risk factors of mortality in stage IIIC primary breast cancer patients and their predictive value. Methods: We extracted data from the US Surveillance, Epidemiology, and End Results (SEER) database of female patients with stage IIIC primary breast cancer (n = 1673) from January 2011 to December 2015. Results: Hormone receptor negativity (P ≤ 0.001 and P ≤ 0.001, respectively), aggressive molecular typing (P ≤ 0.001 and P ≤ 0.001, respectively), high T stage (P ≤ 0.001 and P ≤ 0.001, respectively), a high number of positive lymph nodes (≥14) (P=0.005 and P=0.001, respectively), and lymph node ratio (≥0.8148) (P ≤ 0.001 and P ≤ 0.001, respectively) were associated with poor disease-specific survival. The indicators of disease-specific survival included estrogen receptor status, progesterone receptor status, molecular typing, T stage, number of positive lymph nodes, and lymph node ratio (P ≤ 0.001,P ≤ 0.001,P ≤ 0.001,P ≤ 0.001, P=0.002, and P ≤ 0.001, respectively). Conclusion: Hormone receptor negativity, aggressive molecular typing, high T stage, high number of positive lymph nodes, and lymph node ratio are poor prognostic factors patients with stage IIIC primary breast cancer. The efficient indicators of disease-specific survival include estrogen receptor status, progesterone receptor status, molecular typing, T stage, number of positive lymph nodes, and lymph node ratio.

Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application.

Articular cartilage is susceptible to damage but hard to self-repair due to its avascular nature. Traditional treatment methods are not able to produce satisfactory effects. Mesenchymal stem cells (MSCs) have shown great promise in cartilage repair. However, the therapeutic effect of MSCs is often unstable partly due to their heterogeneity. Understanding the heterogeneity of MSCs and the potential of different types of MSCs for cartilage regeneration will facilitate the selection of superior MSCs for treating cartilage damage. This review provides an overview of the heterogeneity of MSCs at the donor, tissue source and cell immunophenotype levels, including their cytological properties, such as their ability for proliferation, chondrogenic differentiation and immunoregulation, as well as their current applications in cartilage regeneration. This information will improve the precision of MSC-based therapeutic strategies, thus maximizing the efficiency of articular cartilage repair.

Advanced Polymer-Based Drug Delivery Strategies for Meniscal Regeneration.

The meniscus plays a critical role in maintaining knee joint homeostasis. Injuries to the meniscus, especially considering the limited self-healing capacity of the avascular region, continue to be a challenge and are often treated by (partial) meniscectomy, which has been identified to cause osteoarthritis. Currently, meniscus tissue engineering focuses on providing extracellular matrix (ECM)-mimicking scaffolds to direct the inherent meniscal regeneration process, and it has been found that various stimuli are essential. Numerous bioactive factors present benefits in regulating cell fate, tissue development, and healing, but lack an optimal delivery system. More recently, bioengineers have developed various polymer-based drug delivery systems (PDDSs), which are beneficial in terms of the favorable properties of polymers as well as novel delivery strategies. Engineered PDDSs aim to provide not only an ECM-mimicking microenvironment but also the controlled release of bioactive factors with release profiles tailored according to the biological concerns and properties of the factors. In this review, both different polymers and bioactive factors involved in meniscal regeneration are discussed, as well as potential candidate systems, with examples of recent progress. This article aims to summarize drug delivery strategies in meniscal regeneration, with a focus on novel delivery strategies rather than on specific delivery carriers. The current challenges and future prospects for the structural and functional regeneration of the meniscus are also discussed. Impact statement Meniscal injury remains a clinical Gordian knot owing to the limited healing potential of the region, restricted surgical approaches, and risk of inducing osteoarthritis. Existing tissue engineering scaffolds that provide mechanical support and a favorable microenvironment also lack biological cues. Advanced polymer-based delivery strategies consisting of polymers incorporating bioactive factors have emerged as a promising direction. This article primarily reviews the types and applications of biopolymers and bioactive factors in meniscal regeneration. Importantly, various carrier systems and drug delivery strategies are discussed with the hope of inspiring further advancements in this field.

[Fabrication of poly (lactic-co-glycolic acid)/decellularized articular cartilage extracellular matrix scaffold by three-dimensional printing technology and investigating its physicochemical properties].

OBJECTIVE: To manufacture a poly (lactic-co-glycolic acid) (PLGA) scaffold by low temperature deposition three-dimensional (3D) printing technology, prepare a PLGA/decellularized articular cartilage extracellular matrix (DACECM) cartilage tissue engineered scaffold by combining DACECM, and further investigate its physicochemical properties. METHODS: PLGA scaffolds were prepared by low temperature deposition 3D printing technology, and DACECM suspensions was prepared by modified physical and chemical decellularization methods. DACECM oriented scaffolds were prepared by using freeze-drying and physicochemical cross-linking techniques. PLGA/DACECM oriented scaffolds were prepared by combining DACECM slurry with PLGA scaffolds. The macroscopic and microscopic structures of the three kinds of scaffolds were observed by general observation and scanning electron microscope. The chemical composition of DACECM oriented scaffold was analyzed by histological and immunohistochemical stainings. The compression modulus of the three kinds of scaffolds were measured by biomechanical test. Three kinds of scaffolds were embedded subcutaneously in Sprague Dawley rats, and HE staining was used to observe immune response. The chondrocytes of New Zealand white rabbits were isolated and cultured, and the three kinds of cell-scaffold complexes were prepared. The growth adhesion of the cells on the scaffolds was observed by scanning electron microscope. Three kinds of scaffold extracts were cultured with L-929 cells, the cells were cultured in DMEM culture medium as control group, and cell counting kit 8 (CCK-8) was used to detect cell proliferation. RESULTS: General observation and scanning electron microscope showed that the PLGA scaffold had a smooth surface and large pores; the surface of the DACECM oriented scaffold was rough, which was a 3D structure with loose pores and interconnected; and the PLGA/DACECM oriented scaffold had a rough surface, and the large hole and the small hole were connected to each other to construct a vertical 3D structure. Histological and immunohistochemical qualitative analysis demonstrated that DACECM was completely decellularized, retaining the glycosaminoglycans and collagen typeⅡ. Biomechanical examination showed that the compression modulus of DACECM oriented scaffold was significantly lower than those of the other two scaffolds ( P<0.05). There was no significant difference between PLGA scaffold and PLGA/DACECM oriented scaffold ( P>0.05). Subcutaneously embedded HE staining of the three scaffolds showed that the immunological rejections of DACECM and PLGA/DACECM oriented scaffolds were significantly weaker than that of the PLGA scaffold. Scanning electron microscope observation of the cell-scaffold complex showed that chondrocytes did not obviously adhere to PLGA scaffold, and a large number of chondrocytes adhered and grew on PLGA/DACECM oriented scaffold and DACECM oriented scaffold. CCK-8 assay showed that with the extension of culture time, the number of cells cultured in the three kinds of scaffold extracts and the control group increased. There was no significant difference in the absorbance ( A) value between the groups at each time point ( P>0.05). CONCLUSION: The PLGA/DACECM oriented scaffolds have no cytotoxicity, have excellent physicochemical properties, and may become a promising scaffold material of tissue engineered cartilage.

Autologous-cell-derived, tissue-engineered cartilage for repairing articular cartilage lesions in the knee: study protocol for a randomized controlled trial.

BACKGROUND: Spontaneous recovery from articular cartilage injury is difficult, and the ongoing progression of disease can eventually lead to osteoarthritis. Currently, there is no effective non-surgical treatment for articular cartilage injury. Arthroscopic debridement and microfracture surgery are performed for fibrocartilage repair. But fibrocartilage is different from normal articular cartilage, and functional recovery is not satisfactory. Therefore, it is necessary to develop more effective techniques for articular cartilage repair. Progress in material science, cell biology, biomechanics, and bioreactor technology has allowed the development of biomimetic, tissue-engineered osteochondral composites that have shown potential for the repair of damaged cartilage. We prepared biomimetic, tissue-engineered cartilage scaffolds optimized for biochemical composition and structural characteristics. Based on the experience of our pre-clinical studies on animals, a human articular cartilage acellular matrix scaffold was prepared and is in clinical use. The combination of autologous chondrocytes and scaffolds has shown satisfactory results in repairing cartilage defects in preliminary experiments. METHODS: This is a prospective randomized controlled trial. One hundred patients with full-thickness cartilage injury of the knee will be randomly divided into two groups to receive treatment with either tissue-engineered cartilage constructed using biomimetic cartilage extracellular-matrix-oriented scaffolds combined with autologous chondrocytes, or arthroscopic debridement and microfracture surgery. There will be five visiting time points: at baseline, then at 3, 6, 12, and 18 months postoperatively. The primary outcome will be therapeutic efficacy as assessed by the Lysholm score at 12 months postoperatively. The secondary outcomes will be the International Knee Documentation Committee score, Visual Analog Scale score, and cartilage injury and repair as assessed by magnetic resonance imaging as well as the incidence of postoperative adverse events. DISCUSSION: This trial will attempt to verify the use of tissue-engineered cartilage constructed using autologous chondrocytes combined with allogeneic, acellular cartilage matrix for the repair of cartilage defects, thereby providing favorable evidence for its use in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02770209 . Registered on 11 May 2016.

Bioremediation efficiency in the removal of dissolved inorganic nutrients by the red seaweed, Porphyra yezoensis, cultivated in the open sea.

The bioremediation capability and efficiency of large-scale Porphyra cultivation in the removal of inorganic nitrogen and phosphorus from open sea area were studied. The study took place in 2002-2004, in a 300 ha nori farm along the Lusi coast, Qidong County, Jiangsu Province, China, where the valuable rhodophyte seaweed Porphyra yezoensis has been extensively cultivated. Nutrient concentrations were significantly reduced by the seaweed cultivation. During the non-cultivation period of P. yezoensis, the concentrations of NH4-N, NO2-N, NO3-N and PO4-P were 43-61, 1-3, 33-44 and 1-3 micromol L(-1), respectively. Within the Porphyra cultivation area, the average nutrient concentrations during the Porphyra cultivation season were 20.5, 1.1, 27.9 and 0.96 micromol L(-1) for NH4-N, NO2-N, NO3-N and PO4-P, respectively, significantly lower than in the non-cultivation season (p<0.05). Compared with the control area, Porphyra farming resulted in the reduction of NH4-N, NO2-N, NO3-N and PO4-P by 50-94%, 42-91%, 21-38% and 42-67%, respectively. Nitrogen and phosphorus contents in dry Porphyra thalli harvested from the Lusi coast averaged 6.3% and 1.0%, respectively. There were significant monthly variations in tissue nitrogen content (p<0.05) but not in tissue phosphorus content (p>0.05). The highest tissue nitrogen content, 7.65% in dry wt, was found in December and the lowest value, 4.85%, in dry wt, in April. The annual biomass production of P. yezoensis was about 800 kg dry wt ha(-1) at the Lusi Coast in 2003-2004. An average of 14708.5 kg of tissue nitrogen and 2373.5 kg of tissue phosphorus in P. yezoensis biomass were harvested annually from 300 ha of cultivation from Lusi coastal water. These results indicated that Porphyra efficiently removed excess nutrient from nearshore eutrophic coastal areas. Therefore, large-scale cultivation of P. yezoensis could alleviate eutrophication in coastal waters economically.