An in vivo evaluation of a biodegradable genipin-cross-linked gelatin peripheral nerve guide conduit material

Chen, Yueh Sheng; Chang, Ju Ying; Cheng, Chun Yuan; Tsai, Fuu Jen; Yao, Chun Hsu; Liu, Bai Shuan

doi:10.1016/j.biomaterials.2004.09.060

Cited by 184 publications

(117 citation statements)

References 30 publications

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“…It has become a favorite scaffolding material in tissue engineering. [15][16][17][18][19][20] For instance, gelatin can form thermos-reversible hydrogels below their upper critical solution temperature of 25°C-35°C. 21 Gelatinmethacrylamide (GelMA), modification of gelatin with unsaturated methacrylate groups, can be copolymerized to form hydrogel via light or chemical initiators under mild conditions with low cytotoxicity.…”

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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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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“…) than those in the conduits made of various biodegradable materials reported in the literature, such as the chitosan [17], the PLA [2], the PGA [7], the proanthocyanidin (PA) crosslinked gelatine [43] and the genipin cross-linked gelatine (GGT) [22,30]. In addition, the temporal and spatial progresses of cellular activity within the GCC conduit are better than those seen for experiments using silicone rubber nerve guides [41,42], which have largely been used in clinical practice.…”

mentioning

confidence: 99%

Novel use of biodegradable casein conduits for guided peripheral nerve regeneration

Hsiang

Tsai

et al. 2011

J. R. Soc. Interface.

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Recent advances in nerve repair technology have focused on finding more biocompatible, nontoxic materials to imitate natural peripheral nerve components. In this study, casein protein cross-linked with naturally occurring genipin (genipin-cross-linked casein (GCC)) was used for the first time to make a biodegradable conduit for peripheral nerve repair. The GCC conduit was dark blue in appearance with a concentric and round lumen. Water uptake, contact angle and mechanical tests indicated that the conduit had a high stability in water and did not collapse and cramped with a sufficiently high level of mechanical properties. Cytotoxic testing and terminal deoxynucleotidyl transferase dUTP nick-end labelling assay showed that the GCC was non-toxic and non-apoptotic, which could maintain the survival and outgrowth of Schwann cells. Non-invasive real-time nuclear factor-kB bioluminescence imaging accompanied by histochemical assessment showed that the GCC was highly biocompatible after subcutaneous implantation in transgenic mice. Effectiveness of the GCC conduit as a guidance channel was examined as it was used to repair a 10 mm gap in the rat sciatic nerve. Electrophysiology, labelling of calcitonin gene-related peptide in the lumbar spinal cord, and histology analysis all showed a rapid morphological and functional recovery for the disrupted nerves. Therefore, we conclude that the GCC can offer great nerve regeneration characteristics and can be a promising material for the successful repair of peripheral nerve defects.

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“…7 As a result, more attention has been placed on the research of synthetic nerve conduits with different biomaterials; the material of these conduits should also be biocompatible and biodegradable. Currently, materials such as PLLA, 8 genipincross-linked gelatin, 9 collagen, 10,11 silicone, 12 gelatin, 13 laminin, 14 and chitin have been used to prepare nerve conduits. PDLLA is widely applied in drug delivery and tissue engineering scaffold, 15,16 due to its good biocompatibility and mechanical properties; however, its poor cellular affinity limits application in tissue engineering.…”

Section: 6mentioning

confidence: 99%

“…Composite materials with the advantages of biodegradability and biocompatibility are used to imitate the structure and function of natural nerves 9,13,[50][51][52][53] and are commonly used for several biomedical applications. 54 Combined with the advantages of PDLLA, b-TCP and collagen, composite nerve conduits for peripheral nerve regeneration were prepared through electrospinning, and they had excellent mechanical properties, biocompatibility, and neutral microenvironment.…”

Section: 50mentioning

confidence: 99%

Preparation and biocompatibility of electrospinning PDLLA/β-TCP/collagen for peripheral nerve regeneration

Lin

Wang

et al. 2017

RSC Adv.

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A unique nerve conduit composed of poly(D,L-lactic acid) (PDLLA), b-tricalcium phosphate (b-TCP) and collagen was prepared by electrospinning for the first time. Scanning electron microscopy (SEM) showed that the mean diameters of the pores in the nerve conduits were less than 10 mm and greater than 1 mm.These conduits had bionic structures, larger porosity and relatively higher surface area than traditional nerve conduits, thus not only permitting the transportation of nerve growth factor and glucose but also blocking the entry of lymphatic tissue and fibroblasts. The uniform fibers of nerve conduits can mimic the natural extracellular matrix, which is beneficial to cell adhesion, cell proliferation and cell migration.PDLLA/b-TCP/collagen overcomes the challenge of low degradation rate, and maintains the basic pH environment for cell growth. PDLLA/b-TCP/collagen showed good cellular affinity and a low hemolytic rate, which is beneficial for RSC96 Schwann cells adhesion, migration and proliferation. Its good biocompatibility enables its safety in in vivo tests. A 10 mm sciatic nerve defect was bridged in vivo with PDLLA/b-TCP/collagen conduits (c) in Wistar rats. PDLLA groups (a) and PDLLA/b-TCP groups (b) were set and autotransplants (d) were used as control groups. Compared to a and b, c achieved significantly more effective regeneration of sciatic nerve injuries after 3 months' implantation and the mean diameter of soleus muscle fibers in c (39.62 AE 3.91 mm) was 1.28 times larger than that in b (30.89 AE 5.89 mm), and it was closer to that in d. The regenerated nerve fibers in c had a more regular round shape, the density of neurofilaments in c was more than those in a and b, and was close to that in d. PDLLA/b-TCP/ collagen has a bionic structure, good cellular affinity and biodegradability, which can overcome the drawbacks of the current nerve conduits; hence, it holds great promise for effective of sciatic nerve regeneration.

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An in vivo evaluation of a biodegradable genipin-cross-linked gelatin peripheral nerve guide conduit material

Cited by 184 publications

References 30 publications

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

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

Novel use of biodegradable casein conduits for guided peripheral nerve regeneration

Preparation and biocompatibility of electrospinning PDLLA/β-TCP/collagen for peripheral nerve regeneration

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