Elsevier

Acta Biomaterialia

Volume 7, Issue 12, December 2011, Pages 4139-4148
Acta Biomaterialia

Transparent, elastomeric and tough hydrogels from poly(ethylene glycol) and silicate nanoparticles

https://doi.org/10.1016/j.actbio.2011.07.023Get rights and content

Abstract

The structures and mechanical properties of both physically and covalently cross-linked nanocomposite hydrogels made from poly(ethylene glycol) (PEG) and silicate nanoparticles (Laponite RD) are investigated. Injectable nanocomposite precursor solutions can be covalently cross-linked via photopolymerization. The resulting hydrogels are transparent and have interconnected pores, high elongation and toughness. These properties depend on the hydrogel composition, polymer–nanoparticle interactions and degree of cross-linking (both physical and covalent). Covalent cross-linking of polymer chains leads to the formation of an elastic network, whereas physical cross-linking between nanoparticles and polymer chains induces viscoelastic properties. At high deformations covalent bonds may be broken but physical bonds rebuild and to some extent self-heal the overall network structure. Addition of silicate also enhances the bioactivity and adhesiveness of the hydrogel as these materials stick to soft tissue as well as to hard surfaces. In addition, MC3T3-E1 mouse preosteoblast cells readily adhere and spread on nanocomposite hydrogel surfaces. Collectively, the combinations of properties such as elasticity, stiffness, interconnected network, adhesiveness to surfaces and bio-adhesion to cells provide inspiration and opportunities to engineer mechanically strong and elastic tissue matrixes for orthopedic, craniofacial and dental applications.

Graphical abstract

The structures and mechanical properties of both physically and covalently cross-linked nanocomposite hydrogels made from poly (ethylene glycol) (PEG), and silicate nanoparticles (Laponite RD) are investigated. The property combinations that included elasticity, stiffness, interconnected network, adhesiveness to surfaces, and bio-adhesion to cells provide inspiration and opportunities to engineer mechanically strong and elastic tissue matrixes from nanocomposite hydrogels for biomedical applications.

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Introduction

Hydrogels are of great interest for biotechnology, tissue engineering and drug delivery applications due to their hydrophilic character, porous structure and often biocompatible nature [1], [2], [3], [4], [5]. Poly(ethylene glycol) (PEG)-based hydrogels have been extensively used in these applications and a variety of formulations are available [5], [6], [7], [8], [9]. Despite the many advantages of PEG-based hydrogels, they often lack appropriate mechanical properties which limit their application to space-filling scaffolds, soft tissue repair, or matrixes used for delivery of bioactive molecules and cells [10], [11]. To overcome some of these limitations, nanoparticle-containing polymer hydrogels have been developed with properties that can be tailored towards mechanical strength, bioactivity and biocompatibility [12], [13], [14]. Among a variety of nanoparticles, silicates such as Laponite have been used to design and develop mechanically strong nanocomposite polymer hydrogels [12], [13], [14]. Laponite consists of synthetic and charged silicate nanodiscs that may dissolve in aqueous environments under pH-dependent conditions [15]. The chemical composition of these nanoparticles is (Na+0.7[(Mg5.5Li0.3)Si8O20(OH)4]0.7) and the dissolution products include Na+, Si(OH)4, Mg2+, Li+. Similar to bioactive glasses [15], [16], [17], [18], Laponite dissolution products such as Mg2+and Si(OH)4 have been found to enhance osteoblast proliferation and cell differentiation [18], [19], [20], [21].

We are especially interested in evaluating the use of Laponite in polymer hydrogels as compared to other bioactive glass nanoparticles, because the dissolution of Laponite into orthosilicic acid can be accelerated at local lower pH. We found that the presence of H+ from acidic polymer degradation products (e.g. added by formulation with polylactic acid) accelerates the dissolution of the Laponite within the polymer hydrogels. Thus Laponite can be used to establish an internal buffer system within a degradable polymer hydrogel formulation by preventing acidic local environments during polyacid degradation. As a result the in vivo degradation of the Laponite-containing hydrogels should also be faster than the in vitro degradation due to local changes in pH during natural inflammation around an implant. Our group is currently working on evaluating the above-mentioned concepts, and work presented in this paper is the first step towards mapping out the influence of Laponite on some biologically relevant hydrogel properties. In this paper the experiments were performed in a time frame in which the dissolution of Laponite is negligible.

Fundamental research done previously by us and other groups has shown that in aqueous solutions PEG chains readily adsorb to the charged Laponite surfaces via physical interactions [22], [23], [24], [25], [26]. At low concentrations viscoelastic solutions and “shake gels” form [27], [28], and at higher concentrations a variety of physically cross-linked and permanent hydrogels can be generated [13], [24], [29], [30]. More recently, moldable hydrogels were reported, for example, by Wang et al. [31] who used a variety of non-covalent approaches to fabricate nanocomposite hydrogels with high water content from Laponite and dendritic PEG-based macromolecules. These moldable hydrogels have robust mechanical properties and preserved the biological activity of entrapped proteins while maintaining self-healing properties [31].

Although research on physically cross-linked PEG–Laponite solutions and hydrogels goes back more than a decade [22], [32], biomedical relevance has been suggested only recently when cell growth studies showed that cells cultured on the surfaces of poly(ethylene oxide) (PEO)–Laponite gels attach and proliferate easily [19], [33], [34], [35], [36], [37]. The addition of silicate nanoparticles to the bio-inert PEO induced cellular adhesion and proliferation [19], and increased the mechanical strength of the nanocomposite substrate [19], [33]. In a similar study, Pek et al. proposed the use of thixotropic nanocomposite hydrogels made from PEG and silica nanoparticles for three-dimensional cell culture [38]. This group took advantage of the reversible gelation potential of these hydrogels to entrap cells and other biological macromolecules within the network. They showed that differentiation of cells can be controlled by changing the matrix stiffness, which, in turn, can be tuned by varying the concentration of nanoparticles. Collectively, these studies suggest that addition of silicate to PEO hydrogel networks improves some physical as well as biological properties.

While physically cross-linked silicate polymer hydrogels have attractive biological properties, their application as scaffold structures for tissue engineering are limited due to insufficient mechanical properties. However, by covalent cross-linking of polymeric chains in the presence of silicate, mechanically robust and dissolution-resistant hydrogels can be obtained [14], [39]. For example, Fukasawa et al. [40] fabricated such robust hydrogels from tetra-PEG and silicate nanoparticles (Laponite XLG). Uniform dispersion of the silicate nanoparticles and formation of covalently cross-linked networks resulted in mechanically robust hydrogels with high elongations (600–1000%) [40].

In this work, we report on the synthesis and formulation of injectable silicate–PEG nanocomposite precursor solutions that can be covalently cross-linked to form transparent, highly elastic (∼2000% strain) and tough hydrogels. We show that the addition of silicate nanoparticles to the covalently cross-linkable PEG network improves the elongation properties, induces adhesion (stickiness) to soft and hard surfaces, and mammalian cell adhesion. The unique property combinations of the hydrogels reported in this article suggest new approaches to engineering complex viscoelastic biomaterials.

Section snippets

Materials

PEG with a molecular weight Mw of 35000 g mol−1 was purchased from Fluka Analytical (Sigma–Aldrich). The hydroxyl groups of PEG were acrylated by a 5-fold molar excess of acryloyl chloride and a 5-fold molar excess of triethylamine in 100 ml dichloromethane under nitrogen. The reaction was stirred at room temperature for 24 h. The resulting solution was then filtered to remove any precipitates. Afterwards PEG–diacrylate (PEGDA) was precipitated out from the filtrate by pouring into cold diethyl

Results and discussion

The structures and physical properties of the nanocomposite hydrogels presented here are dependent on several parameters such as the composition, nanoparticle characteristics and polymer–nanoparticle interactions. The unique combinations of properties observed in these hydrogels can be attributed to the presence of covalent cross-linking between PEG chains and physical cross-linking between the Laponite nanoparticles and PEG chains.

Conclusions and prospects

The nanocomposite hydrogels investigated here show some unique properties that are a result of combining covalent and physical hydrogel cross-linking techniques. The cross-linking leads to a variety of physical and covalent interactions between silicate nanoparticles and polymers and between polymer chains. Extensible and tough hydrogels were synthesized that could be stretched to more than 1500% of their original size. Addition of silicate induced adhesion to soft and hard surfaces as well as

Acknowledgments

This research has been supported partially by the Purdue Research Foundation and the Weldon School of Biomedical Engineering and partially by an NSF DMR 0711783 award. We would like to acknowledge Dr. Debby Sherman (Life Science Microscopy Facility, Purdue University) for her assistance with cryo-SEM imaging.

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