Controlling the porosity and microarchitecture of hydrogels for tissue engineering

Abstract

Tissue engineering holds great promise for regeneration and repair of diseased tissues, making the development of tissue engineering scaffolds a topic of great interest in biomedical research. Because of their biocompatibility and similarities to native extracellular matrix, hydrogels have emerged as leading candidates for engineered tissue scaffolds. However, precise control of hydrogel properties, such as porosity, remains a challenge. Traditional techniques for creating bulk porosity in polymers have demonstrated success in hydrogels for tissue engineering; however, often the conditions are incompatible with direct cell encapsulation. Emerging technologies have demonstrated the ability to control porosity and the microarchitectural features in hydrogels, creating engineered tissues with structure and function similar to native tissues. In this review, we explore the various technologies for controlling the porosity and microarchitecture within hydrogels, and demonstrate successful applications of combining these techniques.

FIG. 1.

Morphology and in vivo performance of freeze-dried agarose hydrogel scaffolds. Scanning electron microscopy (SEM) images of longitudinal (A) and cross-sectional (B) orientations show linear porosity. Axonal penetration after 1 month in vivo in a spinal cord injury model in the absence (C) and presence (D) of brain-derived neurotrophic factor. The best sample attained shows axons completely crossing the construct (E). Scale bar: 100 μm. Adapted with permission from Stokols et al.

FIG. 2.

α-Elastin hydrogels fabricated using high-pressure CO₂. SEM images of α-elastin hydrogels fabricated at atmospheric pressure (A) and 60 bar (B, C) [top surface (B), cross section (C)]. Fibroblast cells were shown to attach on the scaffold surface (D). Adapted with permission from Annabi et al.

FIG. 3.

Morphology and in vitro assessment of hyaluronic acid (HA)–based scaffolds. SEM images of electrospun salt-leached HA-based scaffolds at 95:5 (A) and 80:20 (B) ratios of HA:collagen using sodium hydroxide and N,N-dimethyl formamide as a mixed solvent. Laser scanning confocal microscopy (C) and SEM (D) images showed that chondrocytes maintained their typical rounded morphology on an 80:20 HA:collagen scaffold after 3 days. Adapted with permission from Kim et al. Color images available online at www.liebertonline.com/ten.

FIG. 4.

SEM images of chitosan-poly(ɛ-caprolactone) hydrogel scaffold formed by freeze-drying. Hydrogels of pure chitosan (A) and chitosan blended with 50 wt% poly(ɛ-caprolactone) (B). Solutions in 25 vol.% acetic acid were frozen at −196°C and lyophilized at −80°C. Adapted with permission from Sarasam et al.

FIG. 5.

Multilumen poly(ethylene glycol) hydrogel conduits fabricated using stereolithography. Isometric (A, C) and top (B, D) views of a poly(ethylene glycol) hydrogel channels with potential in nerve regeneration. The conduits in (C) and (D) contain green and blue fluorescent particles in the outer and inner region, respectively, demonstrating the ability to fabricate constructs from multiple materials. Scale bars represent 1 mm. Reprinted with permission from Arcaute et al. Color images available online at www.liebertonline.com/ten.

FIG. 6.

Use of sacrificial gelatin to create perfusable microvascular networks. Gelatin patterns are cast in polydimethylsiloxane molds and then encapsulated by collagen (A, B) or fibrin (C, D), and the gelatin is removed via melting at 37°C. Perfusable, one-layer cell-laden structures were created using collagen (A, B) and fibrin (C), and multilayer structures were also demonstrated (D). Reprinted with permission from Golden and Tien. Scale bars are 200 μm for panels A, C, D, 25 μm for panel B, and 50 μm for panel A inset. Color images available online at www.liebertonline.com/ten.

FIG. 7.

Schematic of layer-by-layer hepatic tissue formation. Using incremental spacers combined with alternate photomasks allows for the layer-by-layer creation of cell-laden tissues in specific microarchitectural organization (A). Perfusion of micropatterned hepatic tissues demonstrated significant improvements in albumin and urea secretion over unpatterned controls (B, C). Reprinted with permission from Tsang et al. Color images available online at www.liebertonline.com/ten.