Customizing the Shape and Microenvironment Biochemistry of Biocompatible Macroscopic Plant-Derived Cellulose Scaffolds

Abstract

Plant-derived cellulose scaffolds constitute a highly viable and interesting biomaterial. They retain a high flexibility in shape and structure, present the ability to tune surface biochemistry, display a high degree of biocompatibility, exhibit vascularization, and are widely available and easily produced. What is also immediately clear is that pre-existing cellulose structures in plants can also provide candidates for specific tissue engineering applications. Here, we report a new preparation and fabrication approach for producing large scale scaffolds with customizable macroscopic structures that support cell attachment and invasion both in vitro and in vivo. This new fabrication method significantly improves cell attachment compared to that in our previous work. Moreover, the materials remain highly biocompatible and retain vascularization properties in vivo. We present proof-of-concept studies that demonstrate how hydrogels can be temporarily or permanently cast onto the macroscopic scaffolds to create composite plant-derived cellulose biomaterials. This inverse molding approach allows us to provide temporary or permanent biochemical cues to invading cells in vitro. The development of a new-generation of rapidly and efficiently produced composite plant-derived biomaterials provides an important proof that such biomaterials have the potential for numerous applications in tissue engineering.

Plant-derived Cellulose Scaffolds for Bone Tissue Engineering

“…In addition, a large number of cell nuclei was observed around the cellulose pores as well as inside the scaffold pores ( Figures 1D and E). This is consistent with previous studies which showed that various types of cells successfully adhered and proliferated onto plant-derived cellulose scaffolds [14], [16]. Moreover, similarly to one of our previous study [14], we observed that the diameter of the scaffold individual pores was about 154 µm, with the majority of the pores being between 100 and 200 µm ( Figure 2).…”

“…They were then extensively washed with deionized water before permeabilizing the cells with a Triton-X 100 solution (ThermoFisher) for 5 min, and washed again with PBS. Staining of the scaffolds was carried out as previously described [14], [16]. Briefly, the scaffolds were incubated in 1% periodic acid (Sigma-Aldrich) for 40 min.…”

“…In a previous study, our group demonstrated that cellulose-based scaffolds derived from plants, using a simple surfactant treatment, can be used as a material for various tissue reconstruction by taking advantage of the native structure of the plant [14]. Furthermore, these biomaterials can be used for in vitro mammalian cell culture [14], are biocompatible, and can become spontaneously vascularized subcutaneously [14]- [16]. Our group and others have shown that these biomaterials can be sourced from specific plants according to the intended application [14]- [18].…”

“…For instance, the vascular structure from plant stems and leaves displays a similar structure as the one found in animal tissue [18]. Plant-derived cellulose scaffolds can also easily be carved into specific shapes and treated to alter their surface biochemistry [16]. In a recent study, we included a salt buffer in the decellularization process, which resulted in an increase in cell attachment, both in vitro and in vivo [16].…”

“…Scaffolds derived from apple hypanthium tissue were prepared in two formulations that we previously described [14]- [16]. MC3T3-E1 pre-osteoblasts were seeded on bare cellulose scaffolds or composite scaffolds composed of a collagen hydrogel embedded in cellulose scaffolds [16]. Both scaffold preparations supported cellular invasion and proliferation at which point the scaffolds were placed in osteoinductive medium.…”