Biomaterial and Therapeutic Approaches for the Manipulation of Macrophage Phenotype in Peripheral and Central Nerve Repair.

Injury to the peripheral or central nervous systems often results in extensive loss of motor and sensory function that can greatly diminish quality of life. In both cases, macrophage infiltration into the injury site plays an integral role in the host tissue inflammatory response. In particular, the temporally related transition of macrophage phenotype between the M1/M2 inflammatory/repair states is critical for successful tissue repair. In recent years, biomaterial implants have emerged as a novel approach to bridge lesion sites and provide a growth-inductive environment for regenerating axons. This has more recently seen these two areas of research increasingly intersecting in the creation of 'immune-modulatory' biomaterials. These synthetic or naturally derived materials are fabricated to drive macrophages towards a pro-repair phenotype. This review considers the macrophage-mediated inflammatory events that occur following nervous tissue injury and outlines the latest developments in biomaterial-based strategies to influence macrophage phenotype and enhance repair.

A step closer to elastogenesis on demand; Inducing mature elastic fibre deposition in a natural biomaterial scaffold.

Elastic fibres play a key role in bodily functions where fatigue resistance and elastic recovery are necessary while regulating phenotype, proliferation and migration in cells. While in vivo elastic fibres are created at a late foetal stage, a major obstacle in the development of engineered tissue is that human vascular smooth muscle cells (hVSMCs), one of the principal elastogenic cells, are unable to spontaneously promote elastogenesis in vitro. Therefore, the overall aim of this study was to activate elastogenesis in vitro by hVSMCs seeded in fibrin, collagen, glycosaminoglycan (FCG) scaffolds, following the addition of recombinant human tropoelastin. This combination of scaffold, tropoelastin and cells induced the deposition of elastin and formation of lamellar maturing elastic fibres, similar to those found in skin, blood vessels and heart valves. Furthermore, higher numbers of maturing branched elastic fibres were synthesised when a higher cell density was used and by drop-loading tropoelastin onto cell-seeded FCG scaffolds prior to adding growth medium. The addition of tropoelastin showed no effect on cell proliferation or mechanical properties of the scaffold which remained dimensionally stable throughout. With these results, we have established a natural biomaterial scaffold that can undergo controlled elastogenesis on demand, suitable for tissue engineering applications.