Thermoresponsive gelling materials constructed from natural and synthetic polymers can be used to provide triggered action and therefore customised products such as drug delivery and regenerative medicine types as well as for other industries. Some materials give Arrhenius-type viscosity changes based on coil to globule transitions. Others produce more counterintuitive responses to temperature change because of agglomeration induced by enthalpic or entropic drivers. Extensive covalent crosslinking superimposes complexity of response and the upper and lower critical solution temperatures can translate to critical volume temperatures for these swellable but insoluble gels. Their structure and volume response confer advantages for actuation though they lack robustness. Dynamic covalent bonding has created an intermediate category where shape moulding and self-healing variants are useful for several platforms. Developing synthesis methodology-for example, Reversible Addition Fragmentation chain Transfer (RAFT) and Atomic Transfer Radical Polymerisation (ATRP)-provides an almost infinite range of materials that can be used for many of these gelling systems. For those that self-assemble into micelle systems that can gel, the upper and lower critical solution temperatures (UCST and LCST) are analogous to those for simpler dispersible polymers. However, the tuned hydrophobic-hydrophilic balance plus the introduction of additional pH-sensitivity and, for instance, thermochromic response, open the potential for coupled mechanisms to create complex drug targeting effects at the cellular level.
Porosity over a broad range (typically 0.001–300 μm in diameter) of tissue scaffolds provides appropriate conditions for diffusion and adsorption of small molecules and macromolecules, migration of cells through the scaffold, and adequate cell proliferative capacity. Characterisation of pores over this large range poses a problem especially when analysing soft polymer hydrogels, as no one methodology can adequately cover the entire range. This work describes a combined technique used for evaluation of the porous structure of a collagen hydrogel (dermal substitute Integra®) on the basis of NMR-cryoporometry (sensitive to nanopores) and confocal laser scanning microscopy (CLSM) imaging (sensitive to macropores). Thermodesorption of water, diffusion of proteins through a collagen membrane, migration and growth of normal primary human skin fibroblasts, and the interaction kinetics of 3T3 mouse fibroblast cells (using a quartz crystal microbalance) with collagen were analysed with respect to the porous structure of the material. The contribution to the total porosity of pores with a diameter of less than 100 nm is low, at approximately 3–5%, a figure estimated using the methods described above. However, these pores are the main contributor to the specific surface area (S ≈ 120 m2 g−1) as larger diameter macropores, with diameters of 20–200 μm, have a much lower surface area at S ≈ 0.4 m2 g−1 relative to their large pore volume V = 14.4 cm3 g−1
Peripheral nerve injury continues to be a major global health problem that can result in debilitating neurological deficits and neuropathic pain. Current state‐of‐the‐art treatment involves reforming the damaged nerve pathway using a nerve autograft. Engineered nerve repair conduits can provide an alternative to the nerve autograft avoiding the inevitable tissue damage caused at the graft donor site. Commercially available nerve repair conduits are currently only considered suitable for repairing small nerve lesions; the design and performance of engineered conduits requires significant improvements to enable their use for repairing larger nerve defects.
Carbon nanotubes (CNTs) are an emerging novel material for biomedical applications currently being developed for a range of therapeutic technologies including scaffolds for engineering and interfacing with neurological tissues. CNTs possess a unique set of physicochemical properties that could be useful within nerve repair conduits. This progress report aims to evaluate and consolidate the current literature pertinent to CNTs as a biomaterial for supporting peripheral nerve regeneration. The report is presented in the context of the state‐of‐the‐art in nerve repair conduit design; outlining how CNTs may enhance the performance of next generation peripheral nerve repair conduits.
Crosslinked, multi-layer electrospun gelatin fiber scaffolds with generally ±45 degree fiber orientation have been used to grow human umbilical vein smooth muscle cells (HUVSMCs) to create a vascular tunica media graft. Scaffolds of different fiber diameter (2-5 μm in wet state), pore size, and porosity (16-21% in wet state) were assessed in terms of cell adherence and viability, cell proliferation, and migration in both in-plane and transverse directions through the scaffold as a function of time under static cell culture conditions. HUVSMC cell viability reached between 80 and 92% for all scaffolds after 9 days in culture. HUVSMCs adhered, elongated, and orientated in the fiber direction, and migrated through a scaffold thickness of 200-235 μm 9 days post-seeding under static conditions. The best scaffold was then used to assess the tissue engineering of HUVSMCs under dynamic conditions for a rotating, cell seeded, tubular scaffold in the bioreactor containing the culture medium. Dynamic conditions almost doubled the rate of cell proliferation through the scaffold, forming full tissue throughout a scaffold of 250-300 μm thickness 6 days post-seeding.
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