Introducing Controlled Microporosity in Melt Electrowriting

Abstract

proliferation, differentiation, and ultimately the formation of new tissue. [1][2][3][4][5] Recently, the TE paradigm shifted from the classical cell-based/bioreactor approach to an in situ strategy with the aim to exploit the innate natural regenerative potential. [6] In in situ TE, cell-free scaffolds are implanted to attract and harbor host cells directly at the site of implantation. Key advantages include lower regulatory burden for clinical translation and offthe-shelf availability. [7,8] Cell-free scaffolds have to be carefully engineered to immediately withstand the in situ biomechanical loads, [6] to closely match the mechanical characteristics of the targeted tissue to replace, [9] and provide adequate porosity for cell infiltration. [10] There is a wide variety of technologies to fabricate porous scaffolds, for example, salt leaching, [11] gas foaming, [12] ice templating, [13] and fiber forming techniques [14] such as electrospinning. Solution electrospinning (SES) is one of the most used scaffold fabrication techniques. It generates a whipping jet which is collected on a target and results in a nonwoven fabric of nano-to microfibers, where fiber diameter and pore size are inherently coupled. [15] Melt electrowriting (MEW) is a unique solvent-free fiber forming technique [16] that can produce controlled fibers with a Melt electrowriting (MEW) enables the electric field-assisted digital fabrication of precisely defined scaffold architectures of micron-sized fibers. However, charge accumulation and consequent disruption of the precoded pattern by fiber bridging prevents controlled printing at small interfiber distances. This, together with the periodical layer stacking characteristic for additive manufacturing, typically results in scaffolds with channel-like macroporosity, which need to be combined with other biofabrication techniques to achieve the desired microporosity for cellular infiltration. Therefore, a design strategy is devised to introduce controlled interconnected microporosity directly in MEW scaffolds by an algorithm that creates arrays of bridging-free parallel fibers, angularly shifted from layer to layer and starting at a random point to avoid periodical fiber stacking, and hence channel-like pores while defining micropores. This work hypothesizes that pore size can be controlled, decoupled from fiber diameter, and the mechanical properties, including anisotropy ratio, can be tuned. The authors demonstrate this while leveraging the platform for both flat and seamless tubular scaffolds and characterize them via micro-computed tomography and tensile loading. Lastly, successful cell ingrowth into the micropores and extracellular matrix formation are shown. This platform enables microporous scaffolds entirely via MEW that can be tailored to the architectural and mechanical requirements of the target tissues.

Incorporation of Controlled Release Systems Improves the Functionality of Biodegradable 3D Printed Cardiovascular Implants

“…The authors showed the capability to produce microporous tubular scaffolds with tailored anisotropy. 41 Dip coating is another method which has been combined with 3D printing to produce biodegradable vascular grafts using an indirect 3D printing approach. Indirect vascular printing is an appropriate method allowing the fabrication of intricate structures comprising branches with smaller diameters.…”

“…Although patient-specific implants can be precisely 3D printed, the low resolution of extrusion-based 3D printing technologies limits the production of appropriate microporosity needed to support tissue ingrowth. Next to the improvement of the printing resolution and design strategies, the microporosity can be improved by immersion precipitation 3D printing, by incorporating sacrificial porogens to the printing ink, or by saturating the ink with supercritical CO 2 before printing . Apart from 3D printing, new emerging techniques have been developed to further improve the nanoscale fabrication of heart valves.…”

“…Recently, Mueller and colleagues developed a MEW strategy to obtain microporous scaffolds that would not need to be hybridized with another fabrication technique. The authors showed the capability to produce microporous tubular scaffolds with tailored anisotropy . Dip coating is another method which has been combined with 3D printing to produce biodegradable vascular grafts using an indirect 3D printing approach.…”

“…In this approach, the initial compactly folded stent will expand to branched “Y” shaped tubes . The covered stents were produced by melt electrowriting of a microporous PCL membrane directly on a coronary stent …”

Gradient Biomolecular Immobilization of 3D Structured Poly‐ɛ‐caprolactone Biomaterials toward Functional Engineered Tissue

“…Moreover, cell ingrowth and extracellular matrix formation are demonstrated in the study, suggesting the potential of the developed scaffolds for engineered tissue applications. [32] Lu et al have investigated the effect of voltage configurations on PCL jet landing accuracy, furnishing insights into the process variables that affect the accuracy of the MEW process. The study outcomes contribute to the ongoing efforts to optimize the key MEW process parameters.…”