Seaweed polysaccharide-based hydrogels used for the regeneration of articular cartilage

This manuscript provides an overview of the in vitro and in vivo studies reported in the literature focusing on seaweed polysaccharides based hydrogels that have been proposed for applications in regenerative medicine, particularly, in the field of cartilage tissue engineering. For a better understanding of the main requisites for these specific applications, the main aspects of the native cartilage structure, as well as recognized diseases that affect this tissue are briefly described. Current available treatments are also presented to emphasize the need for alternative techniques. The following part of this review is centered on the description of the general characteristics of algae polysaccharides, as well as relevant properties required for designing hydrogels for cartilage tissue engineering purposes. An in-depth overview of the most well known seaweed polysaccharide, namely agarose, alginate, carrageenan and ulvan biopolymeric gels, that have been proposed for engineering cartilage is also provided. Finally, this review describes and summarizes the translational aspect for the clinical application of alternative systems emphasizing the importance of cryopreservation and the commercial products currently available for cartilage treatment.Authors report no declarations of interest. Authors thank the Portuguese Foundation for Science and Technology (FCT) for the PhD fellowship of Elena G. Popa (SFRH/BD/64070/2009) and research project (MIT/ECE/0047/2009). The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no REGPOT-CT2012-316331-POLARIS

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place

Adipose Stem Cell Microbeads as Production Sources for Chondrogenic Growth Factors

Microencapsulating stem cells in injectable microbeads can enhance delivery and localization, but their ability to act as growth factor production sources is still unknown. To address this concern, growth factor mRNA levels and production from alginate microbeads with encapsulated human adipose stem cells (ASC microbeads) cultured in both growth and chondrogenic media (GM and CM) were measured over a two week period. Human ASCs in microbeads were either commercially purchased (Lonza) or isolated from six human donors and compared to human ASCs on tissue culture polystyrene (TCPS). The effects of crosslinking and alginate compositions on growth factor mRNA levels and production were also determined. Secretion profiles of IGF-I, TGF-ß3 and VEGF-A from commercial human ASC microbeads were linear and at a significantly higher rate than TCPS cultures over two weeks. For human ASCs derived from different donors, microencapsulation increased pthlh and both IGF-I and TGF-ß3 secretion. CM decreased fgf2 and VEGF-A secretion from ASC microbeads derived from the same donor population. Crosslinking microbeads in BaCl2 instead of CaCl2 did not eliminate microencapsulation's beneficial effects, but did decrease IGF-I production. Increasing the guluronate content of the alginate microbead increased IGF-I retention. Decreasing alginate molecular weight eliminated the effects microencapsulation had on increasing IGF-I secretion. This study demonstrated that microencapsulation can enhance chondrogenic growth factor production and that chondrogenic medium treatment can decrease angiogenic growth factor production from ASCs, making these cells a potential source for paracrine factors that can stimulate cartilage regeneration

The relationship between components of tumour inflammatory cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer

BACKGROUND: The importance of the components of host local inflammatory response in determining outcome in primary operable ductal invasive breast cancer is not clear. The aim of this study was to examine the relationship between components of the tumour inflammatory cell infiltrate and standard clinicopathological factors including hormone status (oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)-2), Ki-67 and survival in patients with primary operable invasive ductal breast cancer. METHODS: Tumour inflammatory cell infiltrate, hormone status (ER, PR and HER-2), Ki-67 and standard clinicopathological factors were determined using routine pathological and immuno-histochemical techniques in 468 patients. RESULTS: The large majority (94%) of ductal tumours had evidence of inflammatory cell infiltrate. The general inflammatory cell infiltrate was positively associated with high grade (P<0.001), the absence of ER (P<0.001), the absence of PR (P<0.01), the presence of vascular invasion (P<0.05) and high lymphocytic infiltrate, plasma cell infiltrate, other inflammatory cell infiltrate and macrophage infiltrate (all P<0.001). The median follow-up of the survivors was 165 months. During this period, 93 patients died of their cancer. On univariate analysis, stratified for ER status, tumour size (P<0.01), lymph node involvement (P<0.001), tumour plasma cell infiltrate (P<0.001), other inflammatory cell infiltrate (P<0.05) and treatment (P<0.05) were associated with poorer cancer-specific survival whereas lymphocyte infiltrate (P<0.001) was associated with improved cancer-specific survival. On multivariate analysis, stratified for ER status, lymph node involvement (P<0.05) was independently associated with poorer cancer-specific survival whereas increased tumour lymphocyte infiltrate (P<0.001) was independently associated with improved cancer-specific survival. CONCLUSION: The results of this study show that, using routine histology, the general inflammatory cell infiltrate was a common feature and was positively associated with high grade, the absence of ER, the absence of PR, the presence of vascular invasion and high-grade infiltration of lymphocytes, plasma cells, other inflammatory cells and macrophages. Also, that within a mature cohort of patients, a high lymphocytic infiltrate was associated with improved survival, independent of clinicopathological characteristics including ER status, in primary operable ductal invasive breast cancer. These results rationalise previous work and provide a sound basis for future studies in this important area of breast cancer research

Relationship between preoperative comorbidity, systemic inflammatory response, and survival in patients undergoing curative resection for colorectal cancer.

Besides tumor characteristics, colorectal cancer (CRC) outcomes are also determined by host factors, in particular the systemic inflammatory response. The basis of this relationship with survival is not known; however, systemic inflammation may reflect comorbidity. The present study examines relationships between host factors (including age, comorbidity, deprivation, and systemic inflammation) and survival in CRC. A total of 302 patients underwent curative elective CRC resection between 1997 and 2005. Data was collected on patient comorbidity (Charlson Comorbidity Index [CCI], Lee Cardiac Risk Index [LCRI], National Institute on Aging and National Cancer Institute Comorbidity Index [NIA/NCI], and Adult Comorbidity Evaluation-27 [ACE-27]), systemic inflammatory response (Glasgow Prognostic Score [mGPS]), deprivation [Carstairs Deprivation Index], body mass index, and smoking status. For cancer-specific survival, age (P = 0.047), tumor, node, metastasis system stage (P &lt; 0.001), high-risk Petersen Index (P &lt; 0.001), LCRI (P = 0.021), and mGPS (P &lt; 0.001) were independent factors by multivariate analysis. For overall survival, age (P &lt; 0.001), tumor, node, metastasis system stage (P = 0.001), high-risk Petersen Index (P = 0.002), postoperative infective complications (P = 0.002), ACE-27 (P = 0.008), and mGPS (P &lt; 0.001) were independent factors. Older age related to increasing comorbidity (ACE-27, CCI, LCRI [P &lt; 0.005]) and increased mGPS (P &lt; 0.005). Smoking and deprivation related to increasing comorbidity (P &lt; 0.05). The mGPS was associated with high comorbidity burden assessed with ACE-27 (P = 0.065), CCI (P = 0.016), LCRI (P = 0.095), and NIA/NCI (P = 0.084). Comorbidity does not fully explain the relationship between the mGPS and cancer-specific survival in CRC patients. Furthermore, comorbidity, in particular that measured by the LCRI, is an important independent indicator of cancer survival

Lessons from hands-free data entry in flexible cystoscopy with Glass for future smart assistance

We explore how Google Glass can be used to annotate cystoscopy findings in a hands-free and reproducible manner by surgeons during operations in the sterile environment inspired by the current practice of hand-drawn sketches. We present three data entry variants involving head movements and speech input. In an experiment with 8 surgeons and Foundation Doctors having up to 30 years’ cystoscopy experience at a UK hospital we assessed the feasibility, benefits and draw-backs of the system. We report data entry speed and error rate of input modalities and contrast it with the participants’ feedback on their perception of usability, acceptance, and suitability for deployment. These results offer an expanded analysis of the participants’ feedback compared to a previous analysis. The results highlight the potential of new data entry technologies and point out directions for future improvement of eyewear computers. The findings can be generalised to other endoscopic procedures (e.g. OGD/laryngoscopy) and could be included with-in hospital IT in the future. The source code of the Glass application is available at https://github.com/sussexwearlab/GlassMedicalDataEntry