Open AccessA pilot study of poly(N-isopropylacrylamide)-g-polyethylene glycol and poly(N-isopropylacrylamide)-g-methylcellulose branched copolymers as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord
Author(s) -
Lauren Conova,
Andrea Vernengo,
Ying Jin,
B. Timothy Himes,
Birgit Neuhuber,
Itzhak Fischer,
Anthony M. Lowman
Publication year - 2011
Publication title -
journal of neurosurgery. spine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.722
H-Index - 100
eISSN - 1547-5654
pISSN - 1547-5646
DOI - 10.3171/2011.7.spine11194
Subject(s) - self healing hydrogels , spinal cord injury , polyethylene glycol , poly(n isopropylacrylamide) , medicine , peg ratio , biocompatibility , biomedical engineering , spinal cord , copolymer , materials science , chemistry , polymer chemistry , biochemistry , psychiatry , economics , composite material , metallurgy , polymer , finance
Object The authors investigated the feasibility of using injectable hydrogels, based on poly( N -isopropylacrylamide) (PNIPAAm), lightly cross-linked with polyethylene glycol (PEG) or methylcellulose (MC), to serve as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord. The primary aims of this work were to assess the biocompatibility of the scaffolds by evaluating graft cell survival and the host tissue immune response. The scaffolds were also evaluated for their ability to promote axonal growth through the action of released brain-derived neurotrophic factor (BDNF). Methods The in vivo performance of PNIPAAm- g -PEG and PNIPAAm- g -MC was evaluated using a rodent model of spinal cord injury (SCI). The hydrogels were injected as viscous liquids into the injury site and formed space-filling hydrogels. The host immune response and biocompatibility of the scaffolds were evaluated at 2 weeks by histological and fluorescent immunohistochemical analysis. Commercially available matrices were used as a control and examined for comparison. Results Experiments showed that the scaffolds did not contribute to an injury-related inflammatory response. PNIPAAm- g -PEG was also shown to be an effective vehicle for delivery of cellular transplants and supported graft survival. Additionally, PNIPAAm- g -PEG and PNIPAAm- g -MC are permissive to axonal growth and can serve as injectable scaffolds for local delivery of BDNF. Conclusions Based on the results, the authors suggest that these copolymers are feasible injectable scaffolds for cell grafting into the injured spinal cord and for delivery of therapeutic factors.