Three-dimensional Biomimetic Technology: Novel Biorubber Creates Defined Micro- and Macro-scale Architectures in Collagen Hydrogels

Abstract

Tissue scaffolds play a crucial role in the tissue regeneration process. The ideal scaffold must fulfill several requirements such as having proper composition, targeted modulus, and well-defined architectural features. Biomaterials that recapitulate the intrinsic architecture of in vivo tissue are vital for studying diseases as well as to facilitate the regeneration of lost and malformed soft tissue. A novel biofabrication technique was developed which combines state of the art imaging, three-dimensional (3D) printing, and selective enzymatic activity to create a new generation of biomaterials for research and clinical application. The developed material, Bovine Serum Albumin rubber, is reaction injected into a mold that upholds specific geometrical features. This sacrificial material allows the adequate transfer of architectural features to a natural scaffold material. The prototype consists of a 3D collagen scaffold with 4 and 3 mm channels that represent a branched architecture. This paper emphasizes the use of this biofabrication technique for the generation of natural constructs. This protocol utilizes a computer-aided software (CAD) to manufacture a solid mold which will be reaction injected with BSA rubber followed by the enzymatic digestion of the rubber, leaving its architectural features within the scaffold material.

Spatially and temporally controlled hydrogels for tissue engineering

“…Other materials, such as poly(methylmethacrylate) (PMMA), silicon, PTFE, glass, and metals are also frequently used to produce micromolds, although this often requires a surface functionalization process [36, 37]. Recently, the use of 3D printing has significantly expanded the capabilities and flexibility of fabricating complex master molds [38, 39]. To crosslink the hydrogels in micromolds, different techniques have been used including the use of light (most commonly UV light), heat, and chemicals [31, 34, 40].…”

“…For example, Zhao et al used gelatin as the sacrificial material to cast channels within microfluidic devices made from silk fibroin-based hydrogels [42]. Other sacrificial materials including sugars and proteins have been demonstrated [38]. Hosseini et al generated grooved patterns in gelatin methacryloyl (GelMA) hydrogels using nylon fibers as the sacrificial template [43].…”

Microfluidic Cell Chips for High-Throughput Drug Screening

“…While PDMS has been used widely in construction of biomicrofluidic devices, the manually operative nature of PDMS fabrication becomes a critical limitation of using PDMS in mass production. Alternative materials have been utilized in building biomicrofluidic devices, such as thermoplastic materials (e.g., PMMA: poly methyl-methacrylate, PC: polycarbonate, PTFE: polytetrafluoroethylene, PVDF: polyvinyledene fluoride, and PGS: polyglycerol sebacate) [21][22][23][24][25][26][27][28], paper (e.g., nitrocellulose, off-stoichimetry-thoil-ene [OSTE]) [29][30][31], and gelatin with a high melting temperature [32]. In addition, hybrid microfluidic devices using PMMA and PDMS would allow devices to be manufactured easily due to PMMA and have some complexity from PDMS features.…”

Eliminating glutaraldehyde from crosslinked collagen films using supercritical CO2

“…Collagen is versatile and pliable and is used for tissue engineering scaffolds in both the solid and liquid/gel state. Some common fabrication methods for collagen scaffolds include electrospinning, lyophilization, extrusion, and gelation …”