Highly extensible, tough, and elastomeric nanocomposite hydrogels from poly(ethylene glycol) and hydroxyapatite nanoparticles.

Unique combinations of hard and soft components found in biological tissues have inspired researchers to design and develop synthetic nanocomposite gels and hydrogels with elastomeric properties. These elastic materials can potentially be used as synthetic mimics for diverse tissue engineering applications. Here we present a set of elastomeric nanocomposite hydrogels made from poly(ethylene glycol) (PEG) and hydroxyapatite nanoparticles (nHAp). The aqueous nanocomposite PEG-nHAp precursor solutions can be injected and then covalently cross-linked via photopolymerization. The resulting PEG-nHAp hydrogels have interconnected pore sizes ranging from 100 to 300 nm. They have higher extensibilities, fracture stresses, compressive strengths, and toughness when compared with conventional PEO hydrogels. The enhanced mechanical properties are a result of polymer nanoparticle interactions that interfere with the permanent cross-linking of PEG during photopolymerization. The effect of nHAp concentration and temperature on hydrogel swelling kinetics was evaluated under physiological conditions. An increase in nHAp concentration decreased the hydrogel saturated swelling degree. The combination of PEG and nHAp nanoparticles significantly improved the physical and chemical hydrogel properties as well as some biological characteristics such as osteoblast cell adhesion. Further development of these elastomeric materials can potentially lead to use as a matrix for drug delivery and tissue repair especially for orthopedic applications.

Highly extensible bio-nanocomposite fibers.

Here, we show that a poly(ethylene oxide) polymer can be physically cross-linked with silicate nanoparticles (Laponite) to yield highly extensible, bio-nanocomposite fibers that, upon pulling, stretch to extreme lengths and crystallize polymer chains. We find that both, nanometer structures and mechanical properties of the fibers respond to mechanical deformation by exhibiting strain-induced crystallization and high elongation. We explore the structural characteristics using X-ray scattering and the mechanical properties of the dried fibers made from hydrogels in order to determine feasibility for eventual biomedical use and to map out directions for further materials development.

Structural effects of crosslinking a biopolymer hydrogel derived from marine mussel adhesive protein.

In an effort to explore new biocompatible substrates for biomedical technologies, we present a structural study on a crosslinked gelatinous protein extracted from marine mussels. Prior studies have shown the importance of iron in protein crosslinking and mussel adhesive formation. Here, the structure and properties of an extracted material were examined both before and after crosslinking with iron. The structures of these protein hydrogels were studied by SEM, SANS, and SAXS. Viscoelasticity was tested by rheological means. The starting gel was found to have a heterogeneous porous structure on a micrometer scale and, surprisingly, a regular structure on the micron to nanometer scale. However disorder, or "no periodic structure", was deduced from scattering on nanometer length scales at very high q. Crosslinking with iron condensed the structure on a micrometer level. On nanometer length scales at high q, small angle neutron scattering showed no significant differences between the samples, possibly due to strong heterogeneity. X-ray scattering also confirmed the absence of any defined periodic structure. Partial crosslinking transformed the viscoelastic starting gel into one with more rigid and elastic properties.

Robust and adhesive hydrogels from cross-linked poly(ethylene glycol) and silicate for biomedical use.

A systematic approach to develop robust and adhesive hydrogels by photopolymerizing poly(ethylene glycol) (PEG)-diacrylate and methoxy-PEG-acrylate in the presence of charged silicate nanoparticles (Laponite) is presented. PEG-diacrylate and silicate are used for covalent and physical cross-linking, thus providing the hydrogel with mechanical and adhesive strengths. Methoxy-PEG-acrylate is used as a softening agent. The resulting hydrogels can be extensively elongated and the hydrogels readily adhere to tissue even in the elongated state. These hydrogels may aid the development of adhesive tissue engineering matrixes, wound dressings, sealants, and the adhesive components of biomedical devices.

Photocrosslinked nanocomposite hydrogels from PEG and silica nanospheres: structural, mechanical and cell adhesion characteristics.

Photopolymerized hydrogels are extensively investigated for various tissue engineering applications, primarily due to their ability to form hydrogels in a minimally invasive manner. Although photocrosslinkable hydrogels provide necessary biological and chemical characteristics to mimic cellular microenvironments, they often lack sufficient mechanical properties. Recently, nanocomposite approaches have demonstrated potential to overcome these deficits by reinforcing the hydrogel network with. In this study, we investigate some physical, chemical, and biological properties of photocrosslinked poly(ethylene glycol) (PEG)-silica hydrogels. The addition of silica nanospheres significantly suppresses the hydration degree of the PEG hydrogels, indicating surface interactions between the silica nanospheres and the polymer chains. No significant change in hydrogel microstructure or average pore size due to the addition of silica nanospheres was observed. However, addition of silica nanospheres significantly increases both the mechanical strength and the toughness of the hydrogel networks. The biological properties of these nanocomposite hydrogels were evaluated by seeding fibroblast cells on the hydrogel surface. While the PEG hydrogels showed minimum cell adhesion, spreading and proliferation, the addition of silica nanospheres enhanced initial cell adhesion, promoted cell spreading and increased the metabolic activity of the cells. Overall, results indicate that the addition of silica nanospheres improves the mechanical stiffness and cell adhesion properties of PEG hydrogels and can be used for biomedical applications that required controlled cell adhesion.

Robust and semi-interpenetrating hydrogels from poly(ethylene glycol) and collagen for elastomeric tissue scaffolds.

Here we present an injectable PEG/collagen hydrogel system with robust networks for use as elastomeric tissue scaffolds. Covalently crosslinked PEG and physically crosslinked collagen form semi-interpenetrating networks. The mechanical strength of the hydrogels depends predominantely on the PEG concentration but the incorporation of collagen into the PEG network enhances hydrogel viscoelasticity, elongation, and also cell adhesion properties. Experimental data show that this hydrogel system exhibits tunable mechanical properties that can be further developed. The hydrogels allow cell adhesion and proliferation in vitro. The results support the prospect of a robust and semi-interpenetrating biomaterial for elastomeric tissue scaffolds applications.

Physically crosslinked nanocomposites from silicate-crosslinked PEO: mechanical properties and osteogenic differentiation of human mesenchymal stem cells.

The mechanical and biological properties of silicate-crosslinked PEO nanocomposites are studied. A strong correlation is observed between silicate concentration and mechanical properties. In vitro cell culture studies reveal that an increase in silicate concentration enhances the attachment and proliferation of human mesenchymal stem cells significantly. An upregulation in the expression of osteocalcin on nanocomposites compared to the tissue culture polystyrene control is observed. Together, these results suggest that silicate-based nanocomposites are bioactive and have the potential to be used in a range of biotechnological and biomedical applications such as injectable matrices, biomedical coatings, drug delivery, and regenerative medicine.

Recent advances in the development of GTR/GBR membranes for periodontal regeneration--a materials perspective.

UNLABELLED: Periodontitis is a major chronic inflammatory disorder that can lead to the destruction of the periodontal tissues and, ultimately, tooth loss. To date, flap debridement and/or flap curettage and periodontal regenerative therapy with membranes and bone grafting materials have been employed with distinct levels of clinical success. Current resorbable and non-resorbable membranes act as a physical barrier to avoid connective and epithelial tissue down-growth into the defect, favoring the regeneration of periodontal tissues. These conventional membranes possess many structural, mechanical, and bio-functional limitations and the "ideal" membrane for use in periodontal regenerative therapy has yet to be developed. Based on a graded-biomaterials approach, we have hypothesized that the next-generation of guided tissue and guided bone regeneration (GTR/GBR) membranes for periodontal tissue engineering will be a biologically active, spatially designed and functionally graded nanofibrous biomaterial that closely mimics the native extra-cellular matrix (ECM). OBJECTIVE: This review is presented in three major parts, including (1) a brief overview of the periodontium and its pathological conditions, (2) currently employed therapeutics used to regenerate the distinct periodontal tissues, and (3) a review of commercially available GTR/GBR membranes as well as the recent advances on the processing and characterization of GTR/GBR membranes from a materials perspective. SIGNIFICANCE: Studies of spatially designed and functionally graded membranes (FGM) and in vitro antibacterial/cell-related research are addressed. Finally, as a future outlook, the use of hydrogels in combination with scaffold materials is highlighted as a promising approach for periodontal tissue engineering.

Assessment of using laponite cross-linked poly(ethylene oxide) for controlled cell adhesion and mineralization.

The in vitro cytocompatibility of silicate (Laponite clay) cross-linked poly(ethylene oxide) (PEO) nanocomposite films using MC3T3-E1 mouse preosteoblast cells was investigated while cell adhesion, spreading, proliferation and mineralization were assessed as a function of film composition. By combining the advantageous characteristics of PEO polymer (hydrophilic, prevents protein and cell adhesion) with those of a synthetic and layered silicate (charged, degradable and potentially bioactive) some of the physical and chemical properties of the resulting polymer nanocomposites could be controlled. Hydration, dissolution and mechanical properties were examined and related to cell adhesion. Overall, this feasibility study demonstrates the ability of using model Laponite cross-linked PEO nanocomposites to create bioactive scaffolds.

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

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.

Tuning cell adhesion by incorporation of charged silicate nanoparticles as cross-linkers to polyethylene oxide.

Controlling cell adhesion on a biomaterial surface is associated with the long-term efficacy of an implanted material. Here we connect the material properties of nanocomposite films made from PEO physically cross-linked with layered silicate nanoparticles (Laponite) to cellular adhesion. Fibroblast cells do not adhere to pure PEO, but they attach to silicate containing nanocomposites. Under aqueous conditions, the films swell and the degree of swelling depends on the nanocomposite composition and film structure. Higher PEO compositions do not support cell proliferation due to little exposed silicate surfaces. Higher silicate compositions do allow significant cell proliferation and spreading. These bio-nanocomposites have potential for the development of biomedical materials that can control cellular adhesion.

Addition of chitosan to silicate cross-linked PEO for tuning osteoblast cell adhesion and mineralization.

The addition of chitosan to silicate (Laponite) cross-linked poly(ethylene oxide) (PEO) is used for tuning nanocomposite material properties and tailoring cellular adhesion and bioactivity. By combining the characteristics of chitosan (which promotes cell adhesion and growth, antimicrobial) with properties of PEO (prevents protein and cell adhesion) and those of Laponite (bioactive), the resulting material properties can be used to tune cellular adhesion and control biomineralization. Here, we present the hydration, dissolution, degradation, and mechanical properties of multiphase bio-nanocomposites and relate these to the cell growth of MC3T3-E1 mouse preosteoblast cells. We find that the structural integrity of these bio-nanocomposites is improved by the addition of chitosan, but the release of entrapped proteins is suppressed. Overall, this study shows how chitosan can be used to tune properties in Laponite cross-linked PEO for creating bioactive scaffolds to be considered for bone repair.

Silicate cross-linked bio-nanocomposite hydrogels from PEO and chitosan.

The compositions and the multi phase structures of bio-nanocomposite hydrogels made from silicate cross-linked PEO and chitosan are related to some of their physical and biological properties. The gels are injectable and self-healing because the cross-linking is physical and reversible under deformation. The presence of chitosan aggregates affects the viscoelastic properties and reinforces the hydrogel network. The chitosan adds advantageous properties to the hydrogel such as enhanced cell spreading and adhesion. In vitro biocompatibility data indicate that NIH 3T3 fibroblasts grow and proliferate on the bio-nanocomposite hydrogel as well as on hydrogel films.

Heterogeneity in nanocomposite hydrogels from poly(ethylene oxide) cross-linked with silicate nanoparticles.

We investigate the influence of ionic strength on the structural heterogeneity and viscoelastic properties of nanocomposite hydrogels. We use small-angle scattering and rheology to monitor structural changes as a function of ionic strength. Increasing ionic strength makes the nanocomposite gels macroscopically heterogeneous, stiffer and more turbid. At high shear rates, nanometre structures rearrange within aggregates and orient in the flow direction. The changing structural properties that develop with ionic strength are due to increased heterogeneity of nanoparticle distribution and polymer-nanoparticle interactions as well as to the formation of PEO [poly(ethylene oxide)] aggregates interacting with sodium cations, which reinforce the overall hydrogel network.