Cellulose Biomaterials for Tissue Engineering

Abstract

In this review, we highlight the importance of nanostructure of cellulose-based biomaterials to allow cellular adhesion, the contribution of nanostructure to macroscale mechanical properties, and several key applications of these materials for fundamental scientific research and biomedical engineering. Different features on the nanoscale can have macroscale impacts on tissue function. Cellulose is a diverse material with tunable properties and is a promising platform for biomaterial development and tissue engineering. Cellulose-based biomaterials offer some important advantages over conventional synthetic materials. Here we provide an up-to-date summary of the status of the field of cellulose-based biomaterials in the context of bottom-up approaches for tissue engineering. We anticipate that cellulose-based material research will continue to expand because of the diversity and versatility of biochemical and biophysical characteristics highlighted in this review.

Keywords: biocompatibility; biomaterials; cellulose; mechanics; nanostructure.

Figure 1

Schematic of the influence of the local physical and biochemical environment on cell fate and function. Mechanosensing and mechanotransduction are mediated by cell adherence to the substrate via integrins and the interaction of focal adhesions and the cytoskeleton. The ligand type, density, and distribution as well as the matrix stiffness, surface topography, and dimensionality provide distinct cues to the cell and elicit specific responses.

Figure 2

Crystal structure cellulose strands and the corresponding major hydrogen bonding arrangements (Wada et al., 2004). Copyright 2004. Reproduced with permission from Elsevier Inc.

Figure 3

SEM images of cellulose biomaterials. (A) NIH 3T3 cells cultured on a bacterial cellulose film, scale = 10 μm (Fu et al., 2013). Copyright 2013. Reproduced with permission from Elsevier Inc. (B) Schwann cells cultured on a synthetic electrospun cellulose matrix, scale = 100 μm (Naseri-Nosar et al., 2017). Copyright 2017. Reproduced with permission from Elsevier Inc. (C) C2C12 cells cultured on decellularized apple cellulose scaffolds, scale = 50 μm. (Modulevsky et al., 2014) Copyright 2014. Reproduced with permission from PLOS.

Figure 4

Young's modulus of plant materials and human tissues. A small subset of plant candidates are compared to key biological tissue stiffnesses. The source material can be selected to match the elasticity of the native tissue. It should be noted that with processing and modifications the moduli of the plant candidates can be tuned. Adapted from Gibson et al. (2010) with permission from Cambridge University Press.

Figure 5

Human ear scaffolds carved out of plant based cellulose (A) and 3D printed with nanofibrillated cellulose both cultured with human cells (HeLa and chondrocytes, respectively). (A) (Hickey et al., 2018), Copyright 2018. Reproduced with permission from American Chemical Society. (B) (Markstedt et al., 2015), Copyright 2015. Reproduced with permission from American Chemical Society.

Figure 6

Applications of cellulose biomaterials. (A) Skin, (B) nerve, (C) tendon/ligament, (D) larynx, (E) cartilage, (F) bone. (A) (Hakkarainen et al., 2016), Copyright 2016. Reproduced with permission from Elsevier Inc. (B) (Naseri-Nosar et al., 2017), Copyright 2017. Reproduced with permission from Elsevier Inc. (C) (Mathew et al., 2013), Copyright 2013. Reproduced with permission from John Wiley and Sons. (D) (De Souza et al., 2011), Copyright 2011. Reproduced with permission from Elsevier Inc. (E) (Guler et al., 2015), Copyright 2015. Reproduced with permission from John Wiley and Sons. (F) (Park S. et al., 2015) Copyright 2015. Reproduced with permission from Elsevier Inc.