Architecturally defined scaffolds from synthetic collagen and elastin analogues for the fabrication of bioengineered tissues
Caves, Jeffrey Morris
MetadataShow full item record
The microstructure and mechanics of collagen and elastin protein fiber networks dictate the mechanical responses of all soft tissues and related organ systems. In this project, we endeavored to meet or exceed native tissue mechanical properties through mimicry of these extracellular matrix components with synthetic collagen fiber and elastin analogues. Significantly, these studies led to the development of a framework for the design and fabrication of protein-based soft tissue substitutes that reproduced many aspects of native biomechanics. A scalable process was developed for production of synthetic collagen microfibers at a rate of 60 m/hr. Fiber properties and ultrastructure were characterized by uniaxial mechanical testing, differential scanning calorimetry, transmission electron microscopy, and second harmonic generation analysis. In vivo responses to synthetic fibers were evaluated in a murine model. A scalable, semi-automated process was designed for the fabrication of multilamellar membranes comprised of sheets of an elastin analogue reinforced with synthetic collagen fibers. Fibers could be organized in a precisely defined three-dimensional hierarchical pattern. The structure of these fiber composites was analyzed by scanning and transmission electron microscopy, and digital volumetric imaging. The effects of fiber orientation and volume fraction on uniaxial mechanical responses were evaluated. Increased fiber volume fraction and alignment increased Young's modulus, resilience, and yield stress. Highly extensible, elastic tissues display a functionally significant transition from low to high modulus deformation at a transition point strain dictated by the crimped collagen microstructure. This response was replicated by the fabrication of dense arrays of microcrimped synthetic collagen fibers embedded in an elastin analogue. The degree of microcrimping could be varied, and generated a transition point mechanical response. Cyclic tensile deformation did not substantially alter microcrimp morphology. A series of small-diameter vascular grafts consisting of an elastin-like protein reinforced with controlled volume fractions and orientations of synthetic collagen fiber was designed and prototyped. The optimal design satisfied target properties with suture retention strength of 173 ± 4 g-f, burst strength of 1483 ± 143 mm Hg, and compliance of 5.1 ± 0.8 %/100 mm Hg.