Fabrication of Biomaterials via Controlled Protein Bubble Generation and Manipulation

Abstract

In this work, we utilize a recently developed microbubbling process to generate controlled protein (bovine serum albumin, BSA) coated bubbles and then manipulate these to fabricate a variety of structures suitable for several generic biomedical applications, tissue engineering, and biosensor coatings. Using BSA solutions with varying concentrations (20, 25, and 30 wt %) and cross-linking (terephthaloyl chloride) mechanisms, structures were fabricated including porous thin films with variable pore sizes and thickness (partially cross-linked coupled to bubble breakdown), scaffolds with variable pore morphologies (fully cross-linked), and coated bubbles (no cross-linking), which can be used as stand-alone delivery devices and contrast agents. The movement of typical biosensor chemicals (catechol and hydrogen peroxide) across appropriate film structures was studied. The potential of formed scaffold structures for tissue engineering applications was demonstrated using mouse cell lines (L929). In addition to low cost, providing uniform structure generation and high output, the size of the bubbles can easily be controlled by adjusting simplistic processing parameters. The combination of robust processing and chemical modification to uniform macromolecule bubbles can be utilized as a competing, yet novel, tool with current technologies and processes in advancing the biomaterials and biomedical engineering remits.

Formation of Protein and Protein–Gold Nanoparticle Stabilized Microbubbles by Pressurized Gyration

“…The microbubble-forming mechanism is very similar to the coflow phenomenon observed in electrohydrodynamic bubbling. 19 However, unlike electrohydrodynamic bubbling, microbubbles generated using the pressurized gyration process evolve from rapid central rotation, which creates a funnel-like down flow near the tip of the vortex, and the centrifugal force, which opposes the final pinch-off.…”

“…Panels a and c of Figure 3 show that the increase of speed and pressure associated with pressurized gyration can result in the preparation of finer microbubbles. It is also noteworthy that further reduction and size control of the microbubbles can be facilitated by adding surfactants to the liquid carrier 13,18,19 of the bubbling formulation (PVA in this case), and this strategy will also be exploited in our ongoing work on the preparation of nearmonodisperse microbubbles using pressurized gyration. Figure 4 shows a parametric plot constructed for the PVA− lysozyme solution as a function of the rotating speed and working pressure.…”

“…Unlike sonication and microfluidic methods, it gives a high production rate of bubbles and also has the capability to produce near-monodisperse microbubbles. 19 However, this method requires high voltage (kilovolt range), and it might not be suitable for certain healthcare-oriented applications.…”

Biofabrication of Gelatin Tissue Scaffolds with Uniform Pore Size via Microbubble Assembly

“…Recently, a one‐step fabrication method of homogenous and scalable porous alginate films was reported in a study, where nitrogen‐trapped monodispersed alginate microbubbles were obtained through T‐junction microfluidics followed by controlled bursting of these bubbles. The range of material used in microfluidic fabrication of ordered structures is broad and several additional examples can be found in the literature, including poly lactide‐ co ‐glycolide‐ b ‐poly ethylene glycol (PLGA‐ b ‐PEG), phospholipid, alginate, and bovine serum albumin . Although bubble formation and microfluidic dynamics were well studied, there is still a lack of results related with cell culture experiments in 3D fabricated structures.…”

Three‐dimensional porous bioscaffolds for bone tissue regeneration: Fabrication via adaptive foam reticulation and freeze casting techniques, characterization, and cell study

“…It is generally believed that optimization of regeneration capacity of the scaffold depends on the composition and physical and mechanical properties of the scaffold and should be similar to those of the physiological extracellular matrix 17–21. There are reports of other allied methods for various other tissue engineering applications including drug delivery that details the use of bioceramics and biopolymers that are of interest in this area of research 22–24…”