Hydrogel design for supporting neurite outgrowth and promoting gene delivery to maximize neurite extension.
Hydrogels capable of gene delivery provide a combinatorial approach for nerve regeneration, with the hydrogel supporting neurite outgrowth and gene delivery inducing the expression of inductive factors. This report investigates the design of hydrogels that balance the requirements for supporting neurite growth with those requirements for promoting gene delivery. Enzymatically-degradable PEG hydrogels encapsulating dorsal root ganglia explants, fibroblasts, and lipoplexes encoding nerve growth factor were gelled within channels that can physically guide neurite outgrowth. Transfection of fibroblasts increased with increasing concentration of Arg-Gly-Asp (RGD) cell adhesion sites and decreasing PEG content. The neurite length increased with increasing RGD concentration within 10% PEG hydrogels, yet was maximal within 7.5% PEG hydrogels at intermediate RGD levels. Delivering lipoplexes within the gel produced longer neurites than culture in NGF-supplemented media or co-culture with cells exposed to DNA prior to encapsulation. Hydrogels designed to support neurite outgrowth and deliver gene therapy vectors locally may ultimately be employed to address multiple barriers that limit regeneration.
Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Road, Tech E136, Evanston, Illinois 60208-3120, USA.
Jaclyn A
JA
Shepard
Alyson C
AC
Stevans
Samantha
S
Holland
Christine E
CE
Wang
Ariella
A
Shikanov
Lonnie D
LD
Shea
D000818:Animals; D002642:Chick Embryo; D005347:Fibroblasts / Q000502:physiology; D005727:Ganglia, Spinal / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D016501:Neurites / Q000502:physiology*; D009924:Organ Culture Techniques / Q000379:methods; D011092:Polyethylene Glycols / Q000737:chemistry; D014162:Transfection / Q000379:methods
D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols