Silk is a promising material for biomedical applications, and much research is focused on how application-specific, mechanical properties of silk can be designed synthetically through proper amino acid sequences and processing parameters. This protocol describes an iterative process between research disciplines that combines simulation, genetic synthesis, and fiber analysis to better design silk fibers with specific mechanical properties. Computational methods are used to assess the protein polymer structure as it forms an interconnected fiber network through shearing and how this process affects fiber mechanical properties. Model outcomes are validated experimentally with the genetic design of protein polymers that match the simulation structures, fiber fabrication from these polymers, and mechanical testing of these fibers. Through iterative feedback between computation, genetic synthesis, and fiber mechanical testing, this protocol will enable a priori prediction capability of recombinant material mechanical properties via insights from the resulting molecular architecture of the fiber network based entirely on the initial protein monomer composition. This style of protocol may be applied to other fields where a research team seeks to design a biomaterial with biomedical application-specific properties. This protocol highlights when and how the three research groups (simulation, synthesis, and engineering) should be interacting to arrive at the most effective method for predictive design of their material.
Engineered tissues represent an increasingly promising therapeutic approach for correcting structural defects and promoting tissue regeneration in cardiovascular diseases. One of the challenges associated with this approach has been the necessity for the replacement tissue to promote sufficient vascularization to maintain functionality after implantation. This review highlights a number of promising prevascularization design approaches for introducing vasculature into engineered tissues. Although we focus on encouraging blood vessel formation within myocardial implants, we also discuss techniques developed for other tissues that could eventually become relevant to engineered cardiac tissues. Because the ultimate solution to engineered tissue vascularization will require collaboration between wide-ranging disciplines such as developmental biology, tissue engineering, and computational modeling, we explore contributions from each field.
Silk‐elastin‐like‐protein polymers (SELPs) are genetically engineered recombinant protein sequences consisting of repeating units of silk‐like and elastin‐like blocks. By combining these entities, it is shown that both the characteristic strength of silk and the temperature‐dependent responsiveness of elastin can be leveraged to create an enhanced stimuli‐responsive material. It is hypothesized that SELP behavior can be influenced by varying the silk‐to‐elastin ratio. If the responsiveness of the material at different ratios is significantly different, this would allow for the design of materials with specific temperature‐based swelling and mechanical properties. This study demonstrates that SELP fiber properties can be controlled via a temperature transition dependent on the ratio of silk‐to‐elastin in the material. SELP fibers are experimentally wet spun from polymers with different ratios of silk‐to‐elastin and conditioned in either a below or above transition temperature (T t) water bath prior to characterization. The fibers with higher elastin content showed more stimuli‐responsive behavior compared to the fibers with lower elastin content in the hot (57–60 °C) versus cold (4–7 °C) environment, both computationally and experimentally. This work builds a foundation for developing SELP materials with well‐characterized mechanical properties and responsive features.
Objective Neither heart valve repair methods nor current prostheses can accommodate patient growth. Normal aortic and pulmonary valves have three leaflets, and the goal of valve repair and replacement is typically to restore normal three-leaflet morphology. However, mammalian venous valves have bileaflet morphology and open and close effectively over a wide range of vessel sizes. We propose that they might serve as a model for pediatric heart valve reconstruction and replacement valve design. We explore this concept using computer simulation. Methods We use a finite element method to simulate the ability of a reconstructed cardiac semilunar valve to close competently in a growing vessel, comparing a three-leaflet design with a two-leaflet design that mimics a venous valve. Three venous valve designs were simulated to begin to explore the parameter space. Results Simulations show that for an initial vessel diameter of 12 mm, the venous valve design remains competent as the vessel grows to 20 mm (67 %), while the normal semilunar design remains competent only to 13 mm (8 %). Simulations also suggested that systolic function, estimated as effective orifice area, was not detrimentally affected by the venous valve design, with all three venous valve designs exhibiting greater effective orifice area than the semilunar valve design at a given level of vessel growth. Conclusions Morphologic features of the venous valve design make it well-suited for competent closure over a wide range of vessel sizes, suggesting its use as a model for semilunar valve reconstruction in the growing child.
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