Self-assembly using dendritic building blocks - towards controllable nanomaterials

Dendritic molecules have well defined, three-dimensional branched architectures, and constitute a unique nanoscale toolkit. This review focuses on examples in which individual dendritic molecules are assembled into more complex arrays via non-covalent interactions. In particular, it illustrates how the structural information programmed into the dendritic architecture controls the assembly process, and as a consequence, the properties of the supramolecular structures which are generated. Furthermore, the review emphasises how the use of non-covalent (supramolecular) interactions, provides the assembly process with reversibility, and hence a high degree of control. The review also illustrates how self-assembly offers an ideal approach for amplifying the branching of small, synthetically accessible, relatively inexpensive dendritic systems (e.g. dendrons), into highly branched complex nanoscale assemblies.

The review begins by considering the assembly of dendritic molecules to generate discrete, well-defined supramolecular assemblies. The variety of possible assembled structures is illustrated, and the ability of an assembled structure to encapsulate a templating unit is described. The ability of both organic and inorganic building blocks to direct the assembly process is discussed. The review then describes larger discrete assemblies of dendritic molecules, which do not exist as a single well-defined species, but instead exist as statistical distributions. For example, assembly around nanoparticles, the assembly of amphiphilic dendrons and the assembly of dendritic systems in the presence of DNA will all be discussed. Finally, the review examines dendritic molecules, which assemble or order themselves into extended arrays. Such systems extend beyond the nanoscale into the microscale or even the macroscale domain, exhibiting a wide range of different architectures. The ability of these assemblies to act as gel-phase or liquid crystalline materials will be considered.

Taken as a whole, this review emphasises the control and tunability that underpins the assembly of nanomaterials using dendritic building blocks, and furthermore highlights the potential future applications of these assemblies at the interfaces between chemistry, biology and materials science. 

Adult cardiac fibroblast proliferation is modulated by calcium/calmodulin-dependent protein kinase II in normal and hypertrophied hearts

Increased adult cardiac fibroblast proliferation results in an increased collagen deposition responsible for the fibrosis accompanying pathological remodelling of the heart. The mechanisms regulating cardiac fibroblast proliferation remain poorly understood. Using a minimally invasive transverse aortic banding (MTAB) mouse model of cardiac hypertrophy, we have assessed fibrosis and cardiac fibroblast proliferation. We have investigated whether calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) regulates proliferation in fibroblasts isolated from normal and hypertrophied hearts. It is known that CaMKIIδ plays a central role in cardiac myocyte contractility, but nothing is known of its role in adult cardiac fibroblast function. The MTAB model used here produces extensive hypertrophy and fibrosis. CaMKIIδ protein expression and activity is upregulated in MTAB hearts and, specifically, in cardiac fibroblasts isolated from hypertrophied hearts. In response to angiotensin II, cardiac fibroblasts isolated from MTAB hearts show increased proliferation rates. Inhibition of CaMKII with autocamtide inhibitory peptide inhibits proliferation in cells isolated from both sham and MTAB hearts, with a significantly greater effect evident in MTAB cells. These results are the first to show selective upregulation of CaMKIIδ in adult cardiac fibroblasts following cardiac hypertrophy and to assign a previously unrecognised role to CaMKII in regulating adult cardiac fibroblast function in normal and diseased hearts.

Biocompatibility of Calcium Phosphate Bone Cement with Optimised Mechanical Properties

The broad aim of this work was to investigate and optimise the properties of calcium phosphate bone cements (CPCs) for use in vertebroplasty to achieve effective primary fixation of spinal fractures. The incorporation of collagen, both bovine and from a marine sponge (Chondrosia reniformis), into a CPC was investigated. The biological properties of the CPC and collagen-CPC composites were assessed in vitro through the use of human bone marrow stromal cells. Cytotoxicity, proliferation and osteoblastic differentiation were evaluated using lactate dehydrogenase, PicoGreen and alkaline phosphatase activity assays respectively. The addition of both types of collagen resulted in an increase in cytotoxicity, albeit not to a clinically relevant level. Cellular proliferation after 1, 7 and 14 days was unchanged. The osteogenic potential of the CPC was reduced through the addition of bovine collagen but remained unchanged in the case of the marine collagen. These findings, coupled with previous work showing that incorporation of marine collagen in this way can improve the physical properties of CPCs, suggest that such a composite may offer an alternative to CPCs in applications where low setting times and higher mechanical stability are important.

Printability of calcium phosphate: Calcium sulphate powders for the application of tissue engineered bone scaffolds using the 3D printing technique

In this study, calcium phosphate (CaP) powders were blended with a three-dimensional printing (3DP) calcium sulfate (CaSO4)-based powder and the resulting composite powders were printed with a water-based binder using the 3DP technology. Application of a water-based binder ensured the manufacture of CaP:CaSO4 constructs on a reliable and repeatable basis, without long term damage of the printhead. Printability of CaP:CaSO4 powders was quantitatively assessed by investigating the key 3DP process parameters, i.e. in-process powder bed packing, drop penetration behavior and the quality of printed solid constructs. Effects of particle size, CaP:CaSO4 ratio and CaP powder type on the 3DP process were considered. The drop penetration technique was used to reliably identify powder formulations that could be potentially used for the application of tissue engineered bone scaffolds using the 3DP technique. Significant improvements (p < 0.05) in the 3DP process parameters were found for CaP (30-110 μm):CaSO4 powders compared to CaP (< 20 μm):CaSO4 powders. Higher compressive strength was obtained for the powders with the higher CaP:CaSO4 ratio. Hydroxyapatite (HA):CaSO4 powders showed better results than beta-tricalcium phosphate (β-TCP):CaSO4 powders. Solid and porous constructs were manufactured using the 3DP technique from the optimized CaP:CaSO4 powder formulations. High-quality printed constructs were manufactured, which exhibited appropriate green compressive strength and a high level of printing accuracy.

Static and dynamic degradation of sintered calcium phosphate ceramics

The chemical compositions of calcium phosphate materials are similar to that of bone making them very attractive for use in the repair of critical size bone defects. The bioresorption of calcium phosphate occurs principally by dissolution. To determine the impact of composition and flow conditions on dissolution rates, calcium phosphate tablets were prepared by slip casting of ceramic slips with different ratios of hydroxyapatite (HA) and ß-tricalcium phosphate (ß-TCP). Dissolution was evaluated at pH4 using both a static and dynamic flow regime. Both the composition of the HA:ß-TCP tablet and flow regime noticeably influenced the rate of dissolution; the 50:50 HA:ß-TCP composition demonstrating the greatest level of dissolution, and, exposure of the ceramic specimens to dynamic conditions producing the highest rate of dissolution. Understanding the impact of phase composition and flow condition with respect to the dissolution of calcium phosphate will aid in the development and improvement of materials for bone substitution.