GDNF gene delivery via a 2-(dimethylamino)ethyl methacrylate based cyclized knot polymer for neuronal cell applications.

Nonviral genetic therapeutic intervention strategies for neurological disorders hold great promise, but a lack of vector efficacy, coupled with vector toxicity, continue to hinder progress. Here we report the application of a newly developed class of polymer, distinctly different from conventional branched polymers, as a transfection agent for the delivery of glial cell line derived neurotrophic factor (GDNF) encoding gene. This new 2-(dimethylamino)ethyl methacrylate (DMAEMA) based cyclized knot polymer was studied for neuronal cell transfection applications, in comparison to branched polyethyleneimine (PEI). While showing a similar transfection profile over multiple cell types, the cyclized knot polymer showed far lower toxicity. In addition, transfection of Neu7 astrocytes with the GDNF encoding gene was able to cause neurite outgrowth when cocultured with dorsal root ganglia (DRGs). The cyclized knot polymer assessed here (PD-E 8%PEG), synthesized via a simple one-pot reaction, was shown to have great potential for neuronal gene therapy applications.

Electromechanical properties of dried tendon and isoelectrically focused collagen hydrogels.

Assembling artificial collagenous tissues with structural, functional, and mechanical properties which mimic natural tissues is of vital importance for many tissue engineering applications. While the electro-mechanical properties of collagen are thought to play a role in, for example, bone formation and remodeling, this functional property has not been adequately addressed in engineered tissues. Here the electro-mechanical properties of rat tail tendon are compared with those of dried isoelectrically focused collagen hydrogels using piezoresponse force microscopy under ambient conditions. In both the natural tissue and the engineered hydrogel D-periodic type I collagen fibrils are observed, which exhibit shear piezoelectricity. While both tissues also exhibit fibrils with parallel orientations, Fourier transform analysis has revealed that the degree of parallel alignment of the fibrils in the tendon is three times that of the dried hydrogel. The results obtained demonstrate that isoelectrically focused collagen has similar structural and electro-mechanical properties to that of tendon, which is relevant for tissue engineering applications.

Regeneration and repair of tendon and ligament tissue using collagen fibre biomaterials.

Collagen fibres are ubiquitous macromolecular assemblies in nature, providing the structures that support tensile mechanical loads within the human body. Aligned type I collagen fibres are the primary structural motif for tendon and ligament, and therefore biomaterials based on these structures are considered promising candidates for mediating regeneration of these tissues. However, despite considerable investigation, there remains no collagen-fibre-based biomaterial that has undergone clinical evaluation for this application. Recent research in this area has significantly enhanced our understanding of these complex and challenging biomaterials, and is reinvigorating interest in the development of such structures to recapitulate mechanical function. In this review we describe the progress to date towards a ligament or tendon regeneration template based on collagen fibre scaffolds. We highlight reports of particular relevance to the development of the underlying biomaterials science in this area. In addition, the potential for tailoring and manipulating the interactions between collagen fibres and biological systems, as hybrid biomaterial-biological ensembles, is discussed in the context of developing novel tissue engineering strategies for tendon and ligament.