Fig. 8: Hydrogel FBR alters CNS molecular delivery.
a Detail images of BDA (10 kDa) biodistribution released from DCHMO, DCHK, DCHMM, and CHIT at 2 weeks. b Quantification of BDA in tissue compartments adjacent to hydrogels. ***P < 0.0001 versus DCHMO; not significant (NS) for DCHMM versus CHIT c Quantification of the normalized number of BDA-positive neurons at 2 weeks. *P = 0.0375 (DCHMM) and = 0.0413 (CHIT) and NS (DCHK) versus DCHMO. d Quantification of the radial distance to the 50% percentile BDA-positive neuron from the hydrogel-tissue interface. ***P < 0.0001 versus DCHMO. e Quantification of BDA-positive inflammatory cells at 2 weeks. *P = 0.0036, **P = 0.0005 (CD13), = 0.0008 (CD68), ***P < 0.0001 versus DCHMO. *P = 0.0074 (CD13), = 0.003 (CD13 + CD68) and ***P < 0.0001 (CD68) for DCHK versus DCHMM. For all graphs in b–e, n = 6 mice per group. f Detail images showing phenotype of BDA-positive cells adjacent to hydrogel deposits. g Detail images showing increase in cholinergic (ChAT-positive) neuron size in striatum by NGF delivered from DCHMO. h Quantification of increase in cholinergic neuron size normalized to contralateral side at 1 week after injection of 1 µL NGF (1 µg/µl) releasing hydrogels. ***P < 0.0001 and **P = 0.0054 (DCHMM) and = 0.0029 (CHIT) versus DCHMO, NS for DCHMM, and CHIT versus untreated, *P = 0.0429 for DCHMM and = 0.0233 for CHIT versus DCHK respectively, NS between DCHMO and DCHK (n = 5, 6, 5, 5, and 6 mice for DCHMO, DCHK, DCHMM, CHIT, and untreated, respectively). i Principal component Analysis (PCA) for DCHMO, DCHK, DCHMM, and CHIT hydrogels incorporating data from molecular delivery and immunohistochemistry evaluations. j Graphical representation of the positions of hydrogels along PC1 axis (accounting for 64.22% of total variance) with the positive direction representing effective neural molecular delivery while the negative direction represents molecular delivery to inflammatory cells, ***P < 0.0001 for all versus DCHMO, ***P = 0.0007 for DCHK versus DCHMM and ***P < 0.0001 for DCHK versus CHIT, NS for DCHMM versus CHIT (n = 6 mice per group). For all graphs, data are mean ± s.e.m. Statistical analysis using one (c, d, h, j) or two-way (b, e) ANOVA with Bonferroni.
