Thermosensitive heparin‐poloxamer hydrogel encapsulated bFGF and NGF to treat spinal cord injury

Hu, Xiaoli; Li, Rui; Wu, Yanqing; Li, Yang; Zhong, Xingfeng; Zhang, Guanyinsheng; Kang, Yanmin; Liu, Shuhua; Xie, Ling; Ye, Junming; Xiao, Jian

doi:10.1111/jcmm.15478

Cited by 48 publications

(41 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Controlled delivery of multiple GFs to lesion areas is becoming an attractive strategy to achieve successful axonal regrowth following SCI. The HP hydrogel was therefore used for the delivery of both NGF and fibroblast growth factors (bFGF) (Hu et al, 2020). The release of these GFs from the hydrogel exhibited an initial rapid phase during the first week, and a slow sustained release.…”

Section: Polysaccharide-based-hydrogelsmentioning

confidence: 99%

Nerve Growth Factor Biodelivery: A Limiting Step in Moving Toward Extensive Clinical Application?

et al. 2021

View full text Add to dashboard Cite

Nerve growth factor (NGF) was the first-discovered member of the neurotrophin family, a class of bioactive molecules which exerts powerful biological effects on the CNS and other peripheral tissues, not only during development, but also during adulthood. While these molecules have long been regarded as potential drugs to combat acute and chronic neurodegenerative processes, as evidenced by the extensive data on their neuroprotective properties, their clinical application has been hindered by their unexpected side effects, as well as by difficulties in defining appropriate dosing and administration strategies. This paper reviews aspects related to the endogenous production of NGF in healthy and pathological conditions, along with conventional and biomaterial-assisted delivery strategies, in an attempt to clarify the impediments to the clinical application of this powerful molecule.

show abstract

Section: Polysaccharide-based-hydrogelsmentioning

confidence: 99%

Nerve Growth Factor Biodelivery: A Limiting Step in Moving Toward Extensive Clinical Application?

et al. 2021

View full text Add to dashboard Cite

show abstract

“…However, the short half-life of exogenous NGF administration limits its bioactivity and therapeutic effect in vivo . Therefore, developing an efficient delivery of NGF with a hydrogel scaffold may better its bioactivity and provide a controlled-release of NGF, which is beneficial for repair and regeneration of neural injury [ [24] , [25] , [26] ]. By injection or spray-based minimal invasive approach, hydrogels enable remodeling in the lesion, encapsulate cells and/or biomolecules, and accurately fit to any irregular tissue defects [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Injectable hyaluronic acid hydrogel loaded with BMSC and NGF for traumatic brain injury treatment

Wang

Zhang

Ren

et al. 2022

Materials Today Bio

View full text Add to dashboard Cite

Injectable hydrogel has the advantage to fill the defective area and thereby shows promise as therapeutic implant or cell/drug delivery vehicle for tissue repair. In this study, an injectable hyaluronic acid hydrogel in situ dual-enzymatically cross-linked by galactose oxidase (GalOx) and horseradish peroxidase (HRP) was synthesized and optimized, and the therapeutic effect of this hydrogel encapsulated with bone mesenchymal stem cells (BMSC) and nerve growth factors (NGF) for traumatic brain injury (TBI) mice was investigated. Results from in vitro experiments showed that either tyramine-modified hyaluronic acid hydrogels (HT) or NGF loaded HT hydrogels (HT/NGF) possessed good biocompatibility. More importantly, the HT hydrogels loaded with BMSC and NGF could facilitate the survival and proliferation of endogenous neural cells probably by neurotrophic factors release and neuroinflammation regulation, and consequently improved the neurological function recovery and accelerated the repair process in a C57BL/6 TBI mice model. All these findings highlight that this injectable, BMSC and NGF-laden HT hydrogel has enormous potential for TBI and other tissue repair therapy.

show abstract

“…To overcome these shortcomings, in situ delivery systems have been designed to allow local diffusion of bFGF in the lesion area of spinal cord. Therefore, hydrogel and other biomaterials loading growth factors (GFs) have been well developed and widely applied for SCI ( Wang et al, 2017 ; Wang et al, 2019 ; Albashari et al, 2020 ; Hu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

ALG-bFGF Hydrogel Inhibiting Autophagy Contributes to Protection of Blood–Spinal Cord Barrier Integrity via PI3K/Akt/FOXO1/KLF4 Pathway After SCI

Zhang

Xie

et al. 2022

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Promoting blood–spinal cord barrier (BSCB) repair at the early stage plays a crucial role in treatment of spinal cord injury (SCI). Excessive activation of autophagy can prevent recovery of BSCB after SCI. Basic fibroblast growth factor (bFGF) has been shown to promote BSCB repair and locomotor function recovery in SCI. However, the therapeutic effect of bFGF via direct administration on SCI is limited because of its rapid degradation and dilution at injury site. Based on these considerations, controlled release of bFGF in the lesion area is becoming an attractive strategy for SCI repair. At present, we have designed a sustained-release system of bFGF (called ALG-bFGF) using sodium alginate hydrogel, which is able to load large amounts of bFGF and suitable for in situ administration of bFGF in vivo. Here, traumatic SCI mice models and oxygen glucose deprivation (OGD)–stimulated human brain microvascular endothelial cells were performed to explore the effects and the underlying mechanisms of ALG-bFGF in promoting SCI repair. After a single in situ injection of ALG-bFGF hydrogel into the injured spinal cord, sustained release of bFGF from ALG hydrogel distinctly prevented BSCB destruction and improved motor functional recovery in mice after SCI, which showed better therapeutic effect than those in mice treated with bFGF solution or ALG. Evidences have demonstrated that autophagy is involved in maintaining BSCB integrity and functional restoration in animals after SCI. In this study, SCI/OGD exposure–induced significant upregulations of autophagy activation-related proteins (Beclin1, ATG5, LC3II/I) were distinctly decreased by ALG-bFGF hydrogel near the baseline and not less than it both in vivo and in vitro, and this inhibitory effect contributed to prevent BSCB destruction. Finally, PI3K inhibitor LY294002 and KLF4 inhibitor NSC-664704 were applied to further explore the underlying mechanism by which ALG-bFGF attenuated autophagy activation to alleviate BSCB destruction after SCI. The results further indicated that ALG-bFGF hydrogel maintaining BSCB integrity by inhibiting autophagy activation was regulated by PI3K/Akt/FOXO1/KLF4 pathway. In summary, our current study revealed a novel mechanism by which ALG-bFGF hydrogel improves BSCB and motor function recovery after SCI, providing an effective therapeutic strategy for SCI repair.

show abstract

Thermosensitive heparin‐poloxamer hydrogel encapsulated bFGF and NGF to treat spinal cord injury

Cited by 48 publications

References 60 publications

Nerve Growth Factor Biodelivery: A Limiting Step in Moving Toward Extensive Clinical Application?

Nerve Growth Factor Biodelivery: A Limiting Step in Moving Toward Extensive Clinical Application?

Injectable hyaluronic acid hydrogel loaded with BMSC and NGF for traumatic brain injury treatment

ALG-bFGF Hydrogel Inhibiting Autophagy Contributes to Protection of Blood–Spinal Cord Barrier Integrity via PI3K/Akt/FOXO1/KLF4 Pathway After SCI

Contact Info

Product

Resources

About