Surface modified cellulose scaffolds for tissue engineering

Abstract

We report the ability of cellulose to support cells without the use of matrix ligands on the surface of the material, thus creating a two-component system for tissue engineering of cells and materials. Sheets of bacterial cellulose, grown from a culture medium containing Acetobacter organism were chemically modified with glycidyltrimethylammonium chloride or by oxidation with sodium hypochlorite in the presence of sodium bromide and 2,2,6,6-tetramethylpipiridine 1-oxyl radical to introduce a positive, or negative, charge, respectively. This modification process did not degrade the mechanical properties of the bulk material, but grafting of a positively charged moiety to the cellulose surface (cationic cellulose) increased cell attachment by 70% compared to unmodified cellulose, while negatively charged, oxidised cellulose films (anionic cellulose), showed low levels of cell attachment comparable to those seen for unmodified cellulose. Only a minimal level of cationic surface derivitisation (ca 3% degree of substitution) was required for increased cell attachment and no mediating proteins were required. Cell adhesion studies exhibited the same trends as the attachment studies, while the mean cell area and aspect ratio was highest on the cationic surfaces. Overall, we demonstrated the utility of positively charged bacterial cellulose in tissue engineering in the absence of proteins for cell attachment.

Synergy in food, energy and advanced materials production from biomass

“…Thus, cellulose continues to amaze researchers as a source of novel features, as in the recent demonstration of the utility of positively charged bacterial cellulose in tissue engineering, for cell attachment in the absence of proteins [33]. The recognition of its amphiphilic character that was recently demonstrated by Lindman et al [34] led to the demonstration of its capability as a graphite exfoliating agent and a component of nanocomposite films that are showing interesting possibilities as electrodes and as substrates in flexible electronics [35].…”

Modulating cell response on cellulose surfaces; tunable attachment and scaffold mechanics

“…Furthermore, a key challenge of tissue engineering is to design scaffolds that direct cells to attach or perform their phenotypic functions, which promote tissue functionality. Cellular responses to the substratum (attachment, proliferation and differentiation) are influenced by many factors including: surface charge (Courtenay et al 2017;Sergeeva et al 2016;Dadsetan et al 2011), surface roughness (Biazar et al 2011;Ranucci and Moghe 2001;Chang and Wang 2011), topology (Berti et al 2013;Dugan et al 2013), the presence of matrix proteins (Watanabe et al 1993;Marklein and Burdick 2010;Schmedlen et al 2002;Hersel et al 2003), and porosity (Ninan et al 2013;Gravel et al 2006;Zaborowska et al 2010), as well as the mechanical properties of the scaffold, such as Young's modulus (Cao et al 2016;Bäckdahl et al 2006;Georges and Janmey 2005).…”

“…Surface modifications of the biomaterial allow tailoring of surface properties without impact on bulk material properties. Thus, through surface modification, the native surfaces of biomaterials can be physically, or chemically, transformed with the primary goal of engineering desired surface chemistry (Ismail et al 2007), topology (Viswanathan et al 2016), reactivity (Ducheyne and Qui 1999), biocompatibility (Lin et al 2015), hydrophilicity (Yang et al 2002), and/or charge (Courtenay et al 2017).…”

“…Furthermore, cellulose nanocrystals have been incorporated into a range of composite materials as reinforcements to produce hybrid scaffolds with stiffer mechanical properties (Kumar and Gupta 2008;Kumar et al 2014;Kumar et al 2017a, b). While native cellulose requires the presence of matrix ligands to facilitate cell attachment due to the lack of integrin binding sites on the substrate (Wu et al 2003;Zou et al 2001;Pelton 2009), chemical modification may be employed to alter surface chemistry, allowing cell attachment (Courtenay et al 2017). Scaffolds produced from cellulose can range from hard composites blended with hydroxyapatite (Jiang et al 2008), to soft hydrogels (Torres-Rendon et al 2015), as well as variably crosslinked materials including oxidised cellulose crosslinked with diamines (Syverud et al 2015), or other crosslinking agents such as glyoxal, glutaraldehyde or diisocyanates (Quero et al 2011;Puspasari et al 2015).…”

“…Previously, we have demonstrated that surface modification, to introduce a positive surface charge to cellulose (Scheme 1), allows cell attachment in the absence of matrix ligands (Courtenay et al 2017). Here we demonstrate the minimal level of surface modification required and combine this with modulation of the mechanical properties of the scaffold material, achieved by crosslinking with glyoxal (Ramires et al 2010), which results in formation of acetal and hemiacetal linkages upon curing (Scheme 2) (Schramm and Rinderer 2000), yielding films with increased elastic moduli depending on degree of crosslinking (Quero et al 2011).…”