A 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

Conova, Lauren; Vernengo, Jennifer; Jin, Ying; Himes, B. Timothy; Neuhuber, Birgit; Fischer, Itzhak; Lowman, Anthony M.

doi:10.3171/2011.7.spine11194

Cited by 31 publications

(31 citation statements)

References 51 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…299,[305][306][307][308][309][310] However, PNIPAM notably shows cytotoxity and is non-biodegradable, 311 which limits its applications in vivo, even though PNIPAM with finite molecular weight can be eliminated via glomerular filtration without in vivo long-term accumulation. To overcome these drawbacks, PNIPAM hydrogels have been established as cell sheets to construct organized hepatocyte or endothelial mono-or multi-layers.…”

Section: Peg and Poly(n-isopropylacrylamide)mentioning

confidence: 98%

“…Many researchers have prepared copolymers containing PEG and PNIPAM as forms including grafting, diblock, triblock, multiblock, and star. [299][300][301][302] Solutions of PEG-PNIPAM copolymers exhibit adequate injection viscosities, high hydrogel strengths, and rapid gelation kinetics. PEG-PNIPAM copolymers form liquid solutions at ambient temperature and become relatively strong elastic hydrogels at body temperature that display unique micelle aggregation behavior in aqueous solutions.…”

Section: Peg and Poly(n-isopropylacrylamide)mentioning

confidence: 98%

See 1 more Smart Citation

Stimuli-Responsive InjectableIn situ-Forming Hydrogels for Regenerative Medicines

Kim

Kwon

et al. 2015

Polymer Reviews

View full text Add to dashboard Cite

Research on injectable in situ-forming hydrogels has been conducted in diverse biomedical applications for a long period. These hydrogels exhibit sol-to-gel phase transition in accordance with the external stimuli such as temperature change. Also, unlike the traditional surgical procedures the hydrogels have the distinct properties of easy management and minimal invasiveness via simple aqueous state injections at target sites. Currently, numerous polymer materials have been reported as potential stimulusinduced in situ-forming hydrogels. In this review, a comprehensive overview of the state-of-the-art of these rapidly developing materials has been outlined. In situ-forming hydrogels formed by electrostatic and hydrophobic interactions as well as their mechanistic characteristics and biomedical applications in regenerative medicine have also been discussed. The review concludes with perspectives on the future of stimulus-induced in situ-forming hydrogels.

show abstract

Section: Peg and Poly(n-isopropylacrylamide)mentioning

confidence: 98%

Section: Peg and Poly(n-isopropylacrylamide)mentioning

confidence: 98%

Stimuli-Responsive InjectableIn situ-Forming Hydrogels for Regenerative Medicines

Kim

Kwon

et al. 2015

Polymer Reviews

View full text Add to dashboard Cite

show abstract

“…Alternatively, engineered cells producing specific regenerative factors can be delivered without the need for repeated administration, as would be required for the direct delivery of 'naked' protein [Conova et al, 2011;Bearat et al, 2012]. The same requirements that make hydrogels suitable for in situ gelation -compatibility with aqueous, noncytotoxic chemistries -enable the hydrogel-mediated delivery of live cells, where cells are embedded in the liquid hydrogel precursor prior to injection and in situ crosslinking [Lu et al, 2012;Liang et al, 2013;Mothe et al, 2013].…”

Section: Delivery Of Therapeutic Agentsmentioning

confidence: 99%

Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal Pressure

Khaing

Ehsanipour

Hofstetter

et al. 2016

Cells Tissues Organs

View full text Add to dashboard Cite

Spinal cord injury (SCI) is a devastating condition that leaves patients with limited motor and sensory function at and below the injury site, with little to no hope of a meaningful recovery. Because of their ability to mimic multiple features of central nervous system (CNS) tissues, injectable hydrogels are being developed that can participate as therapeutic agents in reducing secondary injury and in the regeneration of spinal cord tissue. Injectable biomaterials can provide a supportive substrate for tissue regeneration, deliver therapeutic factors, and regulate local tissue physiology. Recent reports of increasing intraspinal pressure after SCI suggest that this physiological change can contribute to injury expansion, also known as secondary injury. Hydrogels contain high water content similar to native tissue, and many hydrogels absorb water and swell after formation. In the case of injectable hydrogels for the spinal cord, this process often occurs in or around the spinal cord tissue, and thus may affect intraspinal pressure. In the future, predictable swelling properties of hydrogels may be leveraged to control intraspinal pressure after injury. Here, we review the physiology of SCI, with special attention to the current clinical and experimental literature, underscoring the importance of controlling intraspinal pressure after SCI. We then discuss how hydrogel fabrication, injection, and swelling can impact intraspinal pressure in the context of developing injectable biomaterials for SCI treatment.

show abstract

“…6 Our recent in vivo research using PNIPAAm- g -PEG showed that the hydrogel is biocompatible, can be successfully injected into an injury site and gelled in situ to fill and remain in a spinal cord lesion, without contributing to an injury-related inflammatory response. 7 The LCST of PNIPAAm- g -PEG of approximately 32°C allows it to be injected as a viscous liquid at room temperature and solidify in situ without the use of toxic monomers or cross-linkers. 38 …”

mentioning

confidence: 99%

“…Since our prior work indicated that PNIPAAm- g -PEG is permissive to axonal growth with the addition of BDNF, 7 we hypothesized that a BDNF-induced enhancement in the RST response would promote growth of RST axons into and beyond a hydrogel implant, aiding in accelerated functional recovery following a cervical lesion. To assess this, we combined an implant of PNIPAAm- g -PEG copolymer with codissolved BDNF to aid in the promotion of RST axon regeneration following a cervical dorsolateral funiculotomy.…”

mentioning

confidence: 99%

Implications of poly(N-isopropylacrylamide)-g-poly(ethylene glycol) with codissolved brain-derived neurotrophic factor injectable scaffold on motor function recovery rate following cervical dorsolateral funiculotomy in the rat

Grous

Vernengo

Jin

et al. 2013

SPI

Self Cite

View full text Add to dashboard Cite

Object In a follow-up study to their prior work, the authors evaluated a novel delivery system for a previously established treatment for spinal cord injury (SCI), based on a poly(N-isopropylacrylamide) (PNIPAAm), lightly cross-linked with a polyethylene glycol (PEG) injectable scaffold. The primary aim of this work was to assess the recovery of both spontaneous and skilled forelimb function following a cervical dorsolateral funiculotomy in the rat. This injury ablates the rubrospinal tract (RST) but spares the dorsal and ventral corticospinal tract and can severely impair reaching and grasping abilities. Methods Animals received an implant of either PNIPAAm-g-PEG or PNIPAAm-g-PEG + brain-derived neurotrophic factor (BDNF). The single-pellet reach-to-grasp task and the staircase-reaching task were used to assess skilled motor function associated with reaching and grasping abilities, and the cylinder task was used to assess spontaneous motor function, both before and after injury. Results Because BDNF can stimulate regenerating RST axons, the authors showed that animals receiving an implant of PNIPAAm-g-PEG with codissolved BDNF had an increased recovery rate of fine motor function when compared with a control group (PNIPAAm-g-PEG only) on both a staircase-reaching task at 4 and 8 weeks post-SCI and on a single-pellet reach-to-grasp task at 5 weeks post-SCI. In addition, spontaneous motor function, as measured in the cylinder test, recovered to preinjury values in animals receiving PNIPAAm-g-PEG + BDNF. Fluorescence immunochemistry indicated the presence of both regenerating axons and BDA-labeled fibers growing up to or within the host-graft interface in animals receiving PNIPAAm-g-PEG + BDNF. Conclusions Based on their results, the authors suggest that BDNF delivered by the scaffold promoted the growth of RST axons into the lesion, which may have contributed in part to the increased recovery rate.

show abstract

A 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

Cited by 31 publications

References 51 publications

Stimuli-Responsive InjectableIn situ-Forming Hydrogels for Regenerative Medicines

Stimuli-Responsive InjectableIn situ-Forming Hydrogels for Regenerative Medicines

Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal Pressure

Implications of poly(N-isopropylacrylamide)-g-poly(ethylene glycol) with codissolved brain-derived neurotrophic factor injectable scaffold on motor function recovery rate following cervical dorsolateral funiculotomy in the rat

Contact Info

Product

Resources

About