Silk-fibronectin protein alloy fibres support cell adhesion and viability as a high strength, matrix fibre analogue

Silk is a natural polymer with broad utility in biomedical applications because it exhibits general biocompatibility and high tensile material properties. While mechanical integrity is important for most biomaterial applications, proper function and integration also requires biomaterial incorporation into complex surrounding tissues for many physiologically relevant processes such as wound healing. In this study, we spin silk fibroin into a protein alloy fibre with whole fibronectin using wet spinning approaches in order to synergize their respective strength and cell interaction capabilities. Results demonstrate that silk fibroin alone is a poor adhesive surface for fibroblasts, endothelial cells, and vascular smooth muscle cells in the absence of serum. However, significantly improved cell attachment is observed to silk-fibronectin alloy fibres without serum present while not compromising the fibres' mechanical integrity. Additionally, cell viability is improved up to six fold on alloy fibres when serum is present while migration and spreading generally increase as well. These findings demonstrate the utility of composite protein alloys as inexpensive and effective means to create durable, biologically active biomaterials.T32 EB006359 - NIBIB NIH HH

Silk - Its Mysteries, How It Is Made, and How It Is Used

This article reviews fundamental and applied aspects of silk–one of Nature’s most intriguing materials in terms of its strength, toughness, and biological role–in its various forms, from protein molecules to webs and cocoons, in the context of mechanical and biological properties. A central question that will be explored is how the bridging of scales and the emergence of hierarchical structures are critical elements in achieving novel material properties, and how this knowledge can be explored in the design of synthetic materials. We review how the function of a material system at the macroscale can be derived from the interplay of fundamental molecular building blocks. Moreover, guidelines and approaches to current experimental and computational designs in the field of synthetic silklike materials are provided to assist the materials science community in engineering customized fine-tuned biomaterials for biomedical applications.National Science Foundation (U.S.) (U01 EB014976)United States. Air Force. Office of Scientific ResearchUnited States. Army Research Office. Multidisciplinary University Research InitiativeUnited States. Office of Naval Research. Presidential Early Career Award for Scientists and Engineer

Materials by design: Merging proteins and music

Tailored materials with tunable properties are crucial for applications as biomaterials, for drug delivery, as functional coatings, or as lightweight composites. An emerging paradigm in designing such materials is the construction of hierarchical assemblies of simple building blocks into complex architectures with superior properties. We review this approach in a case study of silk, a genetically programmable and processable biomaterial, which, in its natural role serves as a versatile protein fiber with hierarchical organization to provide structural support, prey procurement or protection of eggs. Through an abstraction of knowledge from the physical system, silk, to a mathematical model using category theory, we describe how the mechanism of spinning fibers from proteins can be translated into music through a process that assigns a set of rules that governs the construction of the system. This technique allows one to express the structure, mechanisms and properties of the ‘material’ in a very different domain, ‘music’. The integration of science and art through categorization of structure–property relationships presents a novel paradigm to create new bioinspired materials, through the translation of structures and mechanisms from distinct hierarchical systems and in the context of the limited number of building blocks that universally governs these systems.National Institutes of Health (U.S.) (U01 EB014976)National Science Foundation (U.S.) (CAREER 0642545)National Science Foundation (U.S.) (CBET 1067093)United States. Office of Naval Research (PECASE N00014-10-1-0562)United States. Air Force Office of Scientific Research (FA9550-11-1-0199

Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2–positive breast cancer

© 2018, Hong Kong Academy of Medicine Press. All rights reserved. Introduction: The management of human epidermal growth factor receptor 2 (HER2)–positive breast cancer has changed dramatically with the introduction and widespread use of HER2-targeted therapies. There is, however, relatively limited real-world information about the effectiveness and safety of trastuzumab emtansine (T-DM1) in Hong Kong Chinese patients. We assessed the efficacy and toxicity profiles among local patients with HER2-positive advanced breast cancer who had received T-DM1 therapy in the second-line setting and beyond. Methods: This retrospective study involved five local centres that provide service for over 80% of the breast cancer population in Hong Kong. The study period was from December 2013 to December 2015. Patients were included if they had recurrent or metastatic histologically confirmed HER2+ breast cancer who had progressed after at least one line of anti-HER2 therapy including trastuzumab. Patients were excluded if they received T-DM1 as first-line treatment for recurrent or metastatic HER2+ breast cancer. Patient charts including biochemical and haematological profiles were reviewed for background information, T-DM1 response, and toxicity data. Adverse events were documented during chemotherapy and 28 days after the last dose of medication. Results: Among 37 patients being included in this study, 28 (75.7%) had two or more lines of anti-HER2 agents and 26 (70.3%) had received two or more lines of palliative chemotherapy. Response assessment revealed that three (8.1%) patients had a complete response, eight (21.6%) a partial response, 11 (29.7%) a stable disease, and 12 (32.4%) a progressive disease; three patients could not be assessed. The median duration of response was 17.3 (95% confidence interval, 8.4-24.8) months. The clinical benefit rate (complete response + partial response + stable disease, ≥12 weeks) was 37.8% (95% confidence interval, 22.2%-53.5%). The median progression-free survival was 6.0 (95% confidence interval, 3.3-9.8) months and the median overall survival had not been reached by the data cut-off date. Grade 3 or 4 toxicities included thrombocytopaenia (13.5%), raised alanine transaminase (8.1%), anaemia (5.4%), and hypokalaemia (2.7%). No patient died as a result of toxicities. Conclusions: In patients with HER2-positive advanced breast cancer who have been heavily pretreated with anti-HER2 agents and cytotoxic chemotherapy, T-DM1 is well tolerated and provided a meaningful progression-free survival of 6 months and an overall survival that has not been reached. Further studies to identify appropriate patient subgroups are warranted.Link_to_subscribed_fulltex