Biologically Inspired Scaffolds for Heart Valve Tissue Engineering via Melt Electrowriting

Abstract

Heart valves are characterized to be highly flexible yet tough, and exhibit complex deformation characteristics such as nonlinearity, anisotropy, and viscoelasticity, which are, at best, only partially recapitulated in scaffolds for heart valve tissue engineering (HVTE). These biomechanical features are dictated by the structural properties and microarchitecture of the major tissue constituents, in particular collagen fibers. In this study, the unique capabilities of melt electrowriting (MEW) are exploited to create functional scaffolds with highly controlled fibrous microarchitectures mimicking the wavy nature of the collagen fibers and their load‐dependent recruitment. Scaffolds with precisely‐defined serpentine architectures reproduce the J‐shaped strain stiffening, anisotropic and viscoelastic behavior of native heart valve leaflets, as demonstrated by quasistatic and dynamic mechanical characterization. They also support the growth of human vascular smooth muscle cells seeded both directly or encapsulated in fibrin, and promote the deposition of valvular extracellular matrix components. Finally, proof‐of‐principle MEW trileaflet valves display excellent acute hydrodynamic performance under aortic physiological conditions in a custom‐made flow loop. The convergence of MEW and a biomimetic design approach enables a new paradigm for the manufacturing of scaffolds with highly controlled microarchitectures, biocompatibility, and stringent nonlinear and anisotropic mechanical properties required for HVTE.

A Parameter Study for 3D-Printing Organized Nanofibrous Collagen Scaffolds Using Direct-Write Electrospinning

“…[8]. Polymer melts have been elecrospun in melt electro-writing (MEW) to create organized fibrous scaffolds, but they are incompatible with heat sensitive polymers like collagen [13][14][15][16][17][18]. Additionally, varying polymer solutions and custom equipment make it is necessary to re-optimize methods across laboratories.…”

A mini review on the generation of crimped ultrathin fibers via electrospinning: Materials, strategies, and applications

“…Up to now, electrospun crimped ultrathin fibers have been produced from various polymers, including polyurethane (PU), polyacrylonitrile (PAN), polyamide‐6 (PA6), polycaprolactone (PCL), acrylic, polylactide (PLA), polyvinylidene fluoride (PVDF), poly (L‐lactide‐co‐ε‐caprolactone) (P(LLA‐CL)), poly (L‐lactide‐co‐acryloyl carbonate) (P(LLA‐AC)), poly(lactic‐ co ‐glycolic) acid (PLGA), poly‐L‐lactide (PLLA), and poly(ε‐caprolactone‐co‐acryloyl carbonate) (P(ε‐CL‐AC)), The polymer solutions of these polymers are summarized in Table .…”

“…Saidy et al combined a biomimetic approach and MEW technology to design and fabricate scaffolds with serpentine fiber architecture to mimic the wavy nature of the collagen fibers and their load‐dependent uncrimping and recruitment. They discovered that a controlled biologically inspired fiber architecture leads to scaffolds with highly tunable strain stiffening response and anisotropic and viscoelastic mechanical properties encompassing those of native heart valves.…”

Which Biological Properties of Heart Valves Are Relevant to Tissue Engineering?

“…Recapitulation of the known anisotropic profile of cusp tissue is also essential and will allow tissue engineered valves to expand more in the radial direction than circumferentially, which will assist with the coaptation of the valve cusps during valve closure. Several methods, including newer approaches such as melt electrowriting, have been used to produce anisotropic scaffolds that either mimic, or structurally replicate collagen-like fibrous microarchitecture and associated material behavior (67)(68)(69)(70)(71)(72). Some projects have developed biological scaffolds from different preparations of collagen (73)(74)(75).…”