title: Novel use of biodegradable casein conduits for guided peripheral nerve regeneration.
abstract: Recent advances in nerve repair technology have focused on finding more biocompatible, non-toxic 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-κB 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.
authors.affiliation: Laboratory of Biomaterials, School of Chinese Medicine, China Medical University, Taichung, Taiwan, Republic of China.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Hsiang
authors.forename: Chin-Chuan
authors.initials: CC
authors.lastname: Tsai
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Tin-Yun
authors.initials: TY
authors.lastname: Ho
authors.forename: Chun-Hsu
authors.initials: CH
authors.lastname: Yao
authors.forename: Yueh-Sheng
authors.initials: YS
authors.lastname: Chen
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002364:Caseins / Q000627:therapeutic use*; D004594:Electrophysiology; D048091:Guided Tissue Regeneration / Q000295:instrumentation* / Q000379:methods; D006652:Histological Techniques; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D057889:Iridoid Glycosides / Q000627:therapeutic use; D039823:Iridoids; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000628:therapy*; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries*
chemical_list: D002364:Caseins; D057889:Iridoid Glycosides; D039823:Iridoids; C007834:genipin