Winner of the Young Investigator Award of the Society for Biomaterials (USA) for 2016, 10th World Biomaterials Congress, May 17–22, 2016, Montreal QC, Canada: Aligned microribbon‐like hydrogels for guiding three‐dimensional smooth muscle tissue regeneration

Abstract

Smooth muscle tissue is characterized by aligned structures, which is critical for its contractile functions. Smooth muscle injury is common and can be caused by various diseases and degenerative processes, and there remains a strong need to develop effective therapies for smooth muscle tissue regeneration with restored structures. To guide cell alignment, previously cells were cultured on 2D nano/microgrooved substrates, but such method is limited to fabricating 2D aligned cell sheets only. Alternatively, aligned electrospun nanofiber has been employed as 3D scaffold for cell alignment, but cells can only be seeded post fabrication, and nanoporosity of electrospun fiber meshes often leads to poor cell distribution. To overcome these limitations, we report aligned gelatin-based microribbons (μRBs) as macroporous hydrogels for guiding smooth muscle alignment in 3D. We developed aligned μRB-like hydrogels using wet spinning, which allows easy fabrication of tissue-scale (cm) macroporous matrices with alignment cues and supports direct cell encapsulation. The macroporosity within μRB-based hydrogels facilitated cell proliferation, new matrix deposition, and nutrient diffusion. In aligned μRB scaffold, smooth muscle cells showed high viability, rapid adhesion, and alignment following μRB direction. Aligned μRB scaffolds supported retention of smooth muscle contractile phenotype, and accelerated uniaxial deposition of new matrix (collagen I/IV) along the μRB. In contrast, cells encapsulated in conventional gelatin hydrogels remained round with matrix deposition limited to pericellular regions only. We envision such aligned μRB scaffold can be broadly applicable in growing other anisotropic tissues including tendon, nerves and blood vessel.

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities

“…[142] Spinning techniques can also readily be modified by using a rotating drum/disk or static parallel bar collector in order to generate aligned fibers. [143] Lee et al used a wet spinning process with a rotating collector to directly fabricate aligned alginate microribbon hydrogels for cell encapsulation applications, [144] while both Baek et al and Yang et al have fabricated aligned electrospun polylactic acid (PLA) fibers using rotating drum and static parallel bar collectors respectively. [145,146] These PLA fibers can then be used as templates for gel channels aiming to dictate the growth and orientation of cells within a collagen-based hydrogel.…”

Recent Advances in Macroporous Hydrogels for Cell Behavior and Tissue Engineering

“…A more promising approach is to simultaneously introduce gelatin and macroporous structures into the hydrogels. For example, gelatin macroporous microstrip hydrogels fabricated by wet spinning can be used for a neatly adherent arrangement of cells [ 212 ]. Arginine–glycine–aspartate peptide (RGD) is a peptide derived from fibronectin or collagen, which provides cells with integrin sites and links to integrins that activate cells, thereby allowing cells to adhere to the ECM [ 213 ].…”

“…In addition, pH-dependent electrospun polyacrylonitrile (PAN) hydrogel supports the adhesion of ADSCs and cardiomyocytes along the nanofiber orientation [ 239 ]. Compared with ordinary gelatin–MA hydrogels, wet-spinning-prepared aligned μRB macroporous hydrogels support rapid adhesion and uniform arrangement of human bladder-derived smooth muscle cells (SMCs) instead of maintaining circular shapes, which mimic the anisotropy of the muscle alignment structure [ 212 ]. The 3D printing technology has received considerable attention in recent years.…”

Macroporous Granular Hydrogels Functionalized with Aligned Architecture and Small Extracellular Vesicles Stimulate Osteoporotic Tendon‐To‐Bone Healing

“…[15] Although macroporous hydrogels have demonstrated improved functionality in several types of tissue regeneration, they have never been used for TBH, mainly due to the limited methods for fabricating macroporous hydrogels with aligned architecture. [12,13,16] Few methods are available for preparing highly ordered macroporous hydrogels, including the template method, the fragmentation method of pressing nanoporous hydrogels through a grid, and the method of collecting high-aspect-ratio microgels with a rotating collector. [12,17] For example, micrometer-sized sodium acetate (NaAc)•3H 2 O crystal templates with aligned microstructures were formed by crystallization from a supersaturated NaAc solution.…”

“…[12,13,16] Few methods are available for preparing highly ordered macroporous hydrogels, including the template method, the fragmentation method of pressing nanoporous hydrogels through a grid, and the method of collecting high-aspect-ratio microgels with a rotating collector. [12,17] For example, micrometer-sized sodium acetate (NaAc)•3H 2 O crystal templates with aligned microstructures were formed by crystallization from a supersaturated NaAc solution. [17a] An agarose hydrogel with aligned microstructure and macropores was obtained by removing these micrometersized aligned crystal templates from the hydrogel.…”