Scaffolds from block polyurethanes based on poly(ɛ-caprolactone) (PCL) and poly(ethylene glycol) (PEG) for peripheral nerve regeneration

Niu, Yuqing; Chen, Kevin C.; He, Tao; Yu, Wenying; Huang, Shuiwen; Xu, Kan

doi:10.1016/j.biomaterials.2014.02.013

Cited by 133 publications

(93 citation statements)

References 33 publications

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“…The rat sciatic nerve model is a widely recognized and implemented in the study of peripheral nerve injury [37]. While 10mm defects have been used previously by other groups [38], we elected to use a larger defect to mitigate any chance of spontaneous autologous repair. As our negative controls demonstrate, there was no return of sensory or motor function in animals with defects that were left unrepaired.…”

Section: Discussionmentioning

confidence: 99%

A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers

et al. 2014

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Peripheral nerve injuries can result in lifelong disability. Primary coaptation is the treatment of choice when the gap between transected nerve ends is short. Long nerve gaps seen in more complex injuries often require autologous nerve grafts or nerve conduits implemented into the repair. Nerve grafts, however, cause morbidity and functional loss at donor sites, which are limited in number. Nerve conduits, in turn, lack an internal scaffold to support and guide axonal regeneration, resulting in decreased efficacy over longer nerve gap lengths. By comparison, peptide amphiphiles (PAs) are molecules that can self-assemble into nanofibers, which can be aligned to mimic the native architecture of peripheral nerve. As such, they represent a potential substrate for use in a bioengineered nerve graft substitute. To examine this, we cultured Schwann cells with bioactive PAs (RGDS-PA, IKVAV-PA) to determine their ability to attach to and proliferate within the biomaterial. Next, we devised a PA construct for use in a peripheral nerve critical sized defect model. Rat sciatic nerve defects were created and reconstructed with autologous nerve, PLGA conduits filled with various forms of aligned PAs, or left unrepaired. Motor and sensory recovery were determined and compared among groups. Our results demonstrate that Schwann cells are able to adhere to and proliferate in aligned PA gels, with greater efficacy in bioactive PAs compared to the backbone-PA alone. In vivo testing revealed recovery of motor and sensory function in animals treated with conduit/PA constructs comparable to animals treated with autologous nerve grafts. Functional recovery in conduit/PA and autologous graft groups was significantly faster than in animals treated with empty PLGA conduits. Histological examinations also demonstrated increased axonal and Schwann cell regeneration within the reconstructed nerve gap in animals treated with conduit/PA constructs. These results indicate that PA nanofibers may represent a promising biomaterial for use in bioengineered peripheral nerve repair.

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Section: Discussionmentioning

confidence: 99%

A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers

et al. 2014

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“…Several previous studies have shown that silicone-NGC exhibited slight walking locomotion due to self-recovery of sciatic function. 22,[41][42][43][44] The flexibility and mechanical properties of the NGC is an important factor for nerve regeneration to manipulate and resist stretching forces during implant surgery and to retain their shape during the nerve regeneration process. [24][25][26][27][28][29][30][31] Therefore, it is essential to explore the mechanical characteristics of nerve conduits.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

Shim

Kwon

Lee

et al. 2015

Tissue Engineering Part A

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The present study employed nerve guidance conduits (NGCs) only, which were made of small intestine submucosa (SIS) and poly(caprolactone-co-lactide) (PCLA) to promote nerve regeneration in a peripheral nerve injury (PNI) model with nerve defects of 15 mm. The SIS-and PCLA-NGCs were easily prepared by rolling of a SIS sheet and a bioplotter using PCLA, respectively. The prepared SIS-and PCLA-NGCs fulfilled the general requirement for use as artificial peripheral NGCs such as easy fabrication, reproducibility for mass production, suturability, sterilizability, wettability, and proper mechanical properties to resist collapsing when applied to in vivo implantation. The SIS-and PCLA-NGCs appeared to be well integrated into the host sciatic nerve without causing dislocations and serious inflammation. All NGCs stably maintained their NGC shape for 8 weeks without collapsing, which matched well with the nerve regeneration rate. Staining of the NGCs in the longitudinal direction showed that the regenerated nerves grew successfully from the SIS-and PCLA-NGCs through the sciatic nerve-injured gap and connected from the proximal to distal direction along the NGC axis. SIS-NGCs exhibited a higher nerve regeneration rate than PCLANGCs. Collectively, our results indicate that SIS-and PCLA-NGCs induced nerve regeneration in a PNI model, a finding that has significant implications in the future with regard to the feasibility of clinical nerve regeneration with SIS-and PCLA-NGCs prepared through an easy fabrication method using promising biomaterials.

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“…9,10 Many studies indicate that the scaffold can promote nerve regeneration individually. [11][12][13] However, if combined with growth factors or seed cells, nerve regeneration will get better outcome. 8,14 It is an important yet-to-be-solved problem about how to combine scaffold with growth factors or seed cells to establish an optimal microenvironment efficiently and effectively.…”

Section: Zhuang Et Almentioning

confidence: 99%

Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

Zhuang¹,

Bu²,

Liu³

et al. 2016

IJN

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In this study, we fabricated glial cell-line derived neurotrophic factor (GDNF)-loaded microspheres, then seeded the microspheres in gelatin-methacrylamide hydrogel, which was finally integrated with the commercial bilayer collagen membrane (Bio-Gide ® ). The novel composite of nerve conduit was employed to bridge a 10 mm long sciatic nerve defect in a rat. GDNF-loaded gelatin microspheres had a smooth surface with an average diameter of 3.9±1.8 μm. Scanning electron microscopy showed that microspheres were uniformly distributed in both the GelMA gel and the layered structure. Using enzyme-linked immunosorbent assay, in vitro release studies (pH 7.4) of GDNF from microspheres exhibited an initial burst release during the first 3 days (18.0%±1.3%), and then, a prolonged-release profile extended to 32 days. However, in an acidic condition (pH 2.5), the initial release percentage of GDNF was up to 91.2%±0.9% within 4 hours and the cumulative release percentage of GDNF was 99.2%±0.2% at 48 hours. Then the composite conduct was implanted in a 10 mm critical defect gap of sciatic nerve in a rat. We found that the nerve was regenerated in both conduit and autograft (AG) groups. A combination of electrophysiological assessment and histomorphometry analysis of regenerated nerves showed that axonal regeneration and functional recovery in collagen tube filled with GDNF-loaded microspheres (GM + CT) group were similar to AG group ( P >0.05). Most myelinated nerves were matured and arranged densely with a uniform structure of myelin in a neat pattern along the long axis in the AG and GM + CT groups, however, regenerated nerve was absent in the BLANK group, left the 10 mm gap empty after resection, and the nerve fiber exhibited a disordered arrangement in the collagen tube group. These results indicated that the hybrid system of bilayer collagen conduit and GDNF-loaded gelatin microspheres combined with gelatin-methacrylamide hydrogels could serve as a new biodegradable artificial nerve guide for nerve tissue engineering.

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Scaffolds from block polyurethanes based on poly(ɛ-caprolactone) (PCL) and poly(ethylene glycol) (PEG) for peripheral nerve regeneration

Cited by 133 publications

References 33 publications

A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers

A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers

Evaluation of Small Intestine Submucosa and Poly(caprolactone-co-lactide) Conduits for Peripheral Nerve Regeneration

Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

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