PMID- 26348141
OWN - NLM
STAT- MEDLINE
DCOM- 20160804
LR  - 20220317
IS  - 1878-7568 (Electronic)
IS  - 1742-7061 (Linking)
VI  - 27
DP  - 2015 Nov
TI  - Cell-seeded alginate hydrogel scaffolds promote directed linear axonal 
      regeneration in the injured rat spinal cord.
PG  - 140-150
LID - S1742-7061(15)30095-7 [pii]
LID - 10.1016/j.actbio.2015.09.001 [doi]
AB  - Despite recent progress in enhancing axonal growth in the injured spinal cord, 
      the guidance of regenerating axons across an extended lesion site remains a major 
      challenge. To determine whether regenerating axons can be guided in rostrocaudal 
      direction, we implanted 2mm long alginate-based anisotropic capillary hydrogels 
      seeded with bone marrow stromal cells (BMSCs) expressing brain-derived 
      neurotrophic factor (BDNF) or green fluorescent protein (GFP) as control into a 
      C5 hemisection lesion of the rat spinal cord. Four weeks post-lesion, numerous 
      BMSCs survived inside the scaffold channels, accompanied by macrophages, Schwann 
      cells and blood vessels. Quantification of axons growing into channels 
      demonstrated 3-4 times more axons in hydrogels seeded with BMSCs expressing BDNF 
      (BMSC-BDNF) compared to control cells. The number of anterogradely traced axons 
      extending through the entire length of the scaffold was also significantly higher 
      in scaffolds with BMSC-BDNF. Increasing the channel diameters from 41mum to 64mum 
      did not lead to significant differences in the number of regenerating axons. 
      Lesions filled with BMSC-BDNF without hydrogels exhibited a random axon 
      orientation, whereas axons were oriented parallel to the hydrogel channel walls. 
      Thus, alginate-based scaffolds with an anisotropic capillary structure are able 
      to physically guide regenerating axons. STATEMENT OF SIGNIFICANCE: After injury, 
      regenerating axons have to extend across the lesion site in the injured spinal 
      cord to reestablish lost neuronal connections. While cell grafting and growth 
      factor delivery can promote growth of injured axons, without proper guidance, 
      axons rarely extend across the lesion site. Here, we show that alginate 
      biomaterials with linear channels that are filled with cells expressing the 
      growth-promoting neurotrophin BDNF promote linear axon extension throughout the 
      channels after transplantation to the injured rat spinal cord. Animals that 
      received the same cells but no alginate guidance structure did not show linear 
      axonal growth and axons did not cross the lesion site. Thus, alginate-based 
      scaffolds with a capillary structure are able to physically guide regenerating 
      axons.
CI  - Copyright (c) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights 
      reserved.
FAU - Gunther, Manuel Ingo
AU  - Gunther MI
AD  - Spinal Cord Injury Center, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Weidner, Norbert
AU  - Weidner N
AD  - Spinal Cord Injury Center, Heidelberg University Hospital, Heidelberg, Germany.
FAU - Muller, Rainer
AU  - Muller R
AD  - Department of Physical and Theoretical Chemistry, University of Regensburg, 
      Regensburg, Germany.
FAU - Blesch, Armin
AU  - Blesch A
AD  - Spinal Cord Injury Center, Heidelberg University Hospital, Heidelberg, Germany. 
      Electronic address: armin.blesch@med.uni-heidelberg.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150905
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
RN  - 0 (Alginates)
RN  - 0 (Hydrogels)
SB  - IM
MH  - Alginates/chemistry
MH  - Animals
MH  - Axons/*pathology
MH  - Cells, Cultured
MH  - Equipment Failure Analysis
MH  - Female
MH  - Guided Tissue Regeneration/instrumentation/methods
MH  - Hydrogels/*chemistry
MH  - Mesenchymal Stem Cell Transplantation/*instrumentation
MH  - Nerve Regeneration/physiology
MH  - Prosthesis Design
MH  - Rats
MH  - Rats, Inbred F344
MH  - Spinal Cord Injuries/*pathology/physiopathology/*therapy
MH  - *Tissue Scaffolds
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Axon guidance
OT  - Bone marrow stromal cells
OT  - Brain-derived neurotrophic factor
OT  - Hydrogel
OT  - Regeneration
OT  - Spinal cord injury
EDAT- 2015/09/09 06:00
MHDA- 2016/08/05 06:00
CRDT- 2015/09/09 06:00
PHST- 2015/05/27 00:00 [received]
PHST- 2015/08/18 00:00 [revised]
PHST- 2015/09/01 00:00 [accepted]
PHST- 2015/09/09 06:00 [entrez]
PHST- 2015/09/09 06:00 [pubmed]
PHST- 2016/08/05 06:00 [medline]
AID - S1742-7061(15)30095-7 [pii]
AID - 10.1016/j.actbio.2015.09.001 [doi]
PST - ppublish
SO  - Acta Biomater. 2015 Nov;27:140-150. doi: 10.1016/j.actbio.2015.09.001. Epub 2015 
      Sep 5.