Micropore‐Forming Gelatin Methacryloyl (GelMA) Bioink Toolbox 2.0: Designable Tunability and Adaptability for 3D Bioprinting Applications

Abstract

It is well‐known that tissue engineering scaffolds that feature highly interconnected and size‐adjustable micropores are oftentimes desired to promote cellular viability, motility, and functions. Unfortunately, the ability of precise control over the microporous structures within bioinks in a cytocompatible manner for applications in 3D bioprinting is generally lacking, until a method of micropore‐forming bioink based on gelatin methacryloyl (GelMA) was reported recently. This bioink took advantage of the unique aqueous two‐phase emulsion (ATPE) system, where poly(ethylene oxide) (PEO) droplets are utilized as the porogen. Considering the limitations associated with this very initial demonstration, this article has furthered the understanding of the micropore‐forming GelMA bioinks by conducting a systematic investigation into the additional GelMA types (porcine and fish, different methacryloyl‐modification degrees) and porogen types (PEO, poly(vinyl alcohol), and dextran), as well as the effects of the porogen concentrations and molecular weights on the properties of the GelMA‐based ATPE bioink system. This article exemplifies not only the significantly wider range of micropore sizes achievable and better emulsion stability, but also the improved suitability for both extrusion and digital light processing bioprinting with favorable cellular responses.

Cell Infiltrative Inner Connected Porous Hydrogel Improves Neural Stem Cell Migration and Differentiation for Functional Repair of Spinal Cord Injury

“…GelMA is a temperature-sensitive material that experiences a gel-to-solution (gel-to-sol) transition when the temperature is elevated . Rheological analysis of porous hydrogel was first performed.…”

“…GelMA is a temperature-sensitive material that experiences a gel-tosolution (gel-to-sol) transition when the temperature is elevated. 21 Rheological analysis of porous hydrogel was first It was reported that GelMA was photocured at 4 °C after physical gelation up to 10 5 Pa, which was 8 times higher than that at 37 °C. 26 To mimic the stiffness of the spinal cord tissue (500−1500 Pa), 27 an adaptive storage modulus scaffold for the spinal cord was obtained and the GelMA and porous pre-gel solution were tested at a concentration of 6 wt %, preheated at 37 °C, and then photocured at 5 mW•cm −2 for 30 s. The storage modulus nearly achieved maximum, as shown in Figure 1D,E.…”

“…In contrast to regular hydrogels, it has been shown that microporous hydrogels enhanced cellular ingrowth . The microporous size and microporosity provide essential cues that not only affect its physicochemical performances but also regulate cellular behaviors and functions. , Recently, it has been shown through three-dimensional bioprinting that microporous GelMA hydrogel shows good cell behavior of proliferation and integration with subcutaneous host tissue and facilitates tissue regeneration. , However, high mechanical strength may not be suitable for nerve tissue repair, especially for the spinal cord tissue. Meanwhile, understanding the process of cell response such as stem cell recruitments and inflammation after porous scaffold implantation is still limited and evidence for porous hydrogels in the treatment of SCI is lacking.…”

“…19,20 Recently, it has been shown through threedimensional bioprinting that microporous GelMA hydrogel shows good cell behavior of proliferation and integration with T h i s c o n t e n t i s subcutaneous host tissue and facilitates tissue regeneration. 21,22 However, high mechanical strength may not be suitable for nerve tissue repair, especially for the spinal cord tissue. Meanwhile, understanding the process of cell response such as stem cell recruitments and inflammation after porous scaffold implantation is still limited and evidence for porous hydrogels in the treatment of SCI is lacking.…”

Application Prospect and Preliminary Exploration of GelMA in Corneal Stroma Regeneration

“…GelMA, as a transparent material, fully meets the requirements of the corneal stroma for transparency, and GelMA can satisfy the biocompatibility and mechanical strength requirements for producing biomaterials, as opposed to other biomaterials made from hydrogels. GelMA offers a good habitat for many types of cells to live in, since it is biocompatible [ 92 ], chemically adaptable [ 93 ], and biodegradable [ 88 ]. According to earlier studies, when cells are grown in three-dimensionally organized hydrogels, they have the ability to modify their surroundings to facilitate migration and spread [ 94 ].…”