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

Microvascular blood flow velocities measured with a retinal function imager: inter-eye correlations in healthy controls and an exploration in multiple sclerosis

Abstract Background The retinal microcirculation has been studied in various diseases including multiple sclerosis (MS). However, inter-eye correlations and potential differences of the retinal blood flow velocity (BFV) remain largely unstudied but may be important in guiding eye selection as well as the design and interpretation of studies assessing or utilizing retinal BFV. The primary aim of this study was to determine inter-eye correlations in BFVs in healthy controls (HCs). Since prior studies raise the possibility of reduced BFV in MS eyes, a secondary aim was to compare retinal BFVs between MS eyes, grouped based on optic neuritis (ON) history and HC eyes. Methods Macular arteriole and venule BFVs were determined using a retinal function imager (RFI) in both eyes of 20 HCs. One eye from a total of 38 MS patients comprising 13 eyes with ON (MSON) and 25 eyes without ON (MSNON) history were similarly imaged with RFI. Results OD (right) and OS (left) BFVs were not significantly different in arterioles (OD: 3.95 ± 0.59 mm/s; OS: 4.08 ± 0.60 mm/s, P = 0.10) or venules (OD: 3.11 ± 0.46 mm/s; OS: 3.23 ± 0.52 mm/s, P = 0.06) in HCs. Very strong inter-eye correlations were also found between arteriolar (r = 0.84, P < 0.001) and venular (r = 0.87, P < 0.001) BFVs in HCs. Arteriolar (3.48 ± 0.88 mm/s) and venular (2.75 ± 0.53 mm/s) BFVs in MSNON eyes were significantly lower than in HC eyes (P = 0.009 and P = 0.005, respectively). Similarly, arteriolar (3.59 ± 0.69 mm/s) and venular (2.80 ± 0.45 mm/s) BFVs in MSON eyes were also significantly lower than in HC eyes (P = 0.046 and P = 0.048, respectively). Arteriolar and venular BFVs in MSON and MSNON eyes did not differ from each other (P = 0.42 and P = 0.48, respectively). Conclusions Inter-eye arteriolar and venular BFVs do not differ significantly in HCs and are strongly correlated. Our findings support prior observations that arteriolar and venular BFVs may be reduced in MS eyes. Moreover, this seems to be the case in both MS eyes with and without a history of ON, raising the possibility of global blood flow alterations in MS. Future larger studies are needed to assess differences in BFVs between MSON and MSNON eyes

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