Stimulation of neurite outgrowth by neurotrophins delivered from degradable hydrogels.
Degradable hydrogels are useful vehicles for the delivery of growth factors to promote the regeneration of diseased or damaged tissue. In the central nervous system, there are many instances where the delivery of neurotrophins has great potential in tissue repair, especially for treatment of spinal cord injury. In this work, hydrogels based on poly(ethylene glycol) that form via a photoinitiated polymerization were investigated for the delivery of neurotrophins. The release kinetics of these factors are controlled by changes in the network crosslinking density, which influences neurotrophin diffusion and subsequent release from the gels with total release times ranging from weeks to several months. The release and activity of one neurotrophic factor, ciliary-neurotrophic factor (CNTF), was assessed with a cell-based proliferation assay and an assay for neurite outgrowth from retinal explants. CNTF released from a degradable hydrogel above an explanted retina was able to stimulate outgrowth of a significantly higher number of neurites than controls without CNTF. Finally, unique microsphere/hydrogel composites were developed to simultaneously deliver multiple neurotrophins with individual release rates.
Burdick
Jason A
JA
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E25-342, Cambridge, MA 02139, USA.
Ward
Matthew
M
Liang
Ellen
E
Young
Michael J
MJ
Langer
Robert
R
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000493:pharmacokinetics; D049108:Cell Enlargement / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004900:Erythroblasts / Q000187:drug effects; D005021:Ethylamines / Q000737:chemistry; D006016:Glycolates / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007773:Lactates / Q000138:chemical synthesis / Q000737:chemistry; D019344:Lactic Acid; D051379:Mice; D008863:Microspheres; D009414:Nerve Growth Factors / Q000493:pharmacokinetics / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D020933:Neurotrophin 3 / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012160:Retina / Q000166:cytology / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005021:Ethylamines; D006016:Glycolates; D020100:Hydrogels; D007773:Lactates; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; C088513:poly(lactic acid-ethylene glycol); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C016162:triethylamine