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Bone tissue engineering aims to regenerate defected bones by combining cells, scaffolds, and growth factors. In general, defected bone tissues are treated with barrier membranes or guiding scaffolds to achieve bone restoration. However, the growth rate of bone tissue is slower than that of adjacent soft tissue. Therefore, we propose patient-customizable guided bone regeneration (GBR) and membrane-guided tissue regeneration (GTR) scaffold hybrid constructs for precise bone tissue restoration without dimensional collapse beyond the critical bone defect size. Silk fibroin (SF) nanofiber membranes and poly­(glycolic acid) (PGA) scaffolds were fabricated using electrospinning and hot-melt additive manufacturing methods based on a computer-generated scaffold design. Their manipulation parameters, microstructures, compressive moduli, and biodegradability were investigated. The initial attachment and proliferation of preosteoblasts on a PGA scaffold were analyzed based on seeding efficiency and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The regenerated bone volumes of control and SF–PGA hybrid scaffolds were 14.8 and 21.4%, respectively, after 8 weeks of in vivo rabbit calvarial defect regeneration. The SF–PGA hybrid scaffold group exhibits greater regeneration of bone tissue than the control and PGA scaffold groups, indicating that this is a promising material combination as a GBR–GTR agent.

Porous collagen scaffolds with micropatterned structures are manufactured using preformed ice micropattern templates. The scaffolds show precisely controlled pore structures and micropattern structures of bioactive substances, which can be tethered by designing a program.

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Discrete micropatterns on biomaterial surfaces can be used to guide the direction of mammalian cell movement by orienting cell morphology. However, guiding cell assembly in three-dimensional scaffolds remains a challenge. Here we demonstrate that the random motions of motile cells can be rectified within continuous microchannels without chemotactic gradients or fluid flow. Our results show that uniform width microchannels with an overhanging zigzag design can induce polarization of NIH3T3 fibroblasts and human umbilical vein endothelial cells by expanding the cell front at each turn. These continuous zigzag microchannels can guide the direction of cell movement even for cells with altered intracellular signals that promote random movement. This approach for directing cell migration within microchannels has important potential implications in the design of scaffolds for tissue engineering.

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Development of porous scaffolds with open surface pore structures is required for tissue engineering to deliver cells into the three-dimensional spaces in the scaffolds and improve cell distribution. This study demonstrated a new type of funnel-like chitosan sponge prepared using ice particulates as a template. The funnel-like chitosan sponges had a hierarchical bilayer porous structure of a surface layer and an interconnected bulk porous layer. The top surface porous layer consisted mainly of large open pores. The bulk porous layer was beneath the large surface pores and consisted of small pores that were connected with the large surface pores. The large surface pores were dependent on the shape, dimension, and density of the embossing ice particulates, while the bulk pores were dependent on the freezing temperature. The large open surface pores and interconnected bulk pores in the funnel-like chitosan sponges facilitated cell seeding and cell distribution from the surface into the inner bulk pores. Cells cultured in the funnel-like chitosan sponges showed high viability, high proliferation, and homogenous tissue formation. Such funnel-like chitosan sponges will be useful for tissue engineering.

A new type of collagen sponge was prepared as a tissue engineering scaffold using ice particulates as a template. The sponge has a hierarchical structure of large open pores on the top surface and interconnected small pores in the inner bulk body. The shape, size, and density of the surface large pores were determined by the ice particulates that were used as the template while the interconnected small pores were determined by the freezing temperature. The open and interconnected porous structure of the new collagen sponge facilitated cell seeding, cell penetration, and distribution throughout the scaffold, and accelerated cell proliferation and regeneration of new tissue. These ice particulate templates could be used to create open and interconnected porous scaffold structures.