Article
In vivo evaluation of polysialic acid (polySia) as part of biohybrid nerve transplants
In-vivo-Evaluation von Polysialin-Säure (polySia) als Bestandteil biohybrider Nerventransplantate
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Authors
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K. Haastert
- Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany
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Y. Haile
- Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany
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B. Rode
- Institute of Technical Chemistry, Leibniz University Hannover, Hannover, Germany
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K. Stummeyer
- Institute of Cellular Chemistry, Hannover Medical School, Hannover, Germany
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R. Gerardy-Schahn
- Institute of Cellular Chemistry, Hannover Medical School, Hannover, Germany
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T. Scheper
- Institute of Technical Chemistry, Leibniz University Hannover, Hannover, Germany
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C. Grothe
- Institute of Neuroanatomy, Hannover Medical School, Hannover, Germany
| Published: | May 30, 2008 |
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Outline
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Objective: To avoid autogenous nerve transplantation for reconstruction of peripheral nerves after massive tissue loss, development of new biohybrid nerve transplants (BNT) is desired. Polysialic acid (polySia) is a homopolymer of alpha-2,8-linked sialic acid residues and a posttranslational modification of the neural cell adhesion molecule (NCAM). It has recently been demonstrated that polySia substrate does not impair culture and maintenance of primary neurons and glia cells in vitro [1], which makes it a candidate substance for nerve tissue reconstruction scaffolds. Here we describe the in vivo investigation of the properties of polySia when included into acellular and cellular silicone nerve bridges.
Methods: A 10 mm gap in transected sciatic nerves of adult rats were reconstructed using silicone tubes differentially filled for acellular (n=4) and cellular (n=4+1) transplantation conditions. Acellular transplantation conditions were (A) matrigel (growth factor reduced , BD science), (B) soluble polySia (extracted from capsules of E. coli k1) mixed with matrigel (12.5 mg/ml), (C) polySia-matrigel-mix added with endosialidase (endo N, 1 µg/ml in DMEM). For cellular transplantation conditions (D-F) highly enriched neonatal Schwann cells (SC) were suspendend in the fore mentioned matrices. One additional animal per group was transplanted with SC pre-labeled with the fluorescent cell-linker PKH-GL26.
Results: Three weeks after surgery, macroscopic evaluation revealed 100% nerve transplants including gap-bridging regenerated tissue in the presence of polySia. Microscopic tissue analysis elucidated a significant better survival of pre-labeled SC in the polySia groups where cells were found to be equally distributed over the lengths of the regenerated tissue. Immunocytochemical analysis demonstrated no signs of elevated immunological reaction by exogenous polySia and growth associated protein 43 (GAP-43) was detected on the regenerating axons as sign for no interference of polySia with axonal outgrowth.
Conclusions: This short-term study demonstrates the biocompatibility of polySia in vivo and shows its promising potential to be used in scaffolds for peripheral nerve reconstruction. Long term evaluation as well as evaluation of regeneration across even longer gaps is currently on the way.
Finacially supported by DFG-FOR-548/1
K. Haastert and Y. Haile contributed equally to this study.
References
- 1.
- Haile Y, Haastert K, Cesnulevicius K, Stummeyer K, Timmer M, Berski S, Drager G, Gerardy-Schahn R, Grothe C. Culturing of glial and neuronal cells on polysialic acid. Biomaterials. 2007;28:1163-73.
