PMID- 30014962
OWN - NLM
STAT- MEDLINE
DCOM- 20190930
LR  - 20190930
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 180
DP  - 2018 Oct
TI  - Induced neuro-vascular interactions robustly enhance functional attributes of 
      engineered neural implants.
PG  - 1-11
LID - S0142-9612(18)30470-8 [pii]
LID - 10.1016/j.biomaterials.2018.07.001 [doi]
AB  - Engineered neural implants have a myriad of potential basic science and clinical 
      neural repair applications. Although there are implants that are currently 
      undergoing their first clinical investigations, optimizing their long-term 
      viability and efficacy remain an open challenge. Functional implants with 
      pre-vascularization of various engineered tissues have proven to enhance 
      post-implantation host integration, and well-known synergistic neural-vascular 
      interplays suggest that this strategy could also be promising for neural tissue 
      engineering. Here, we report the development of a novel bio-engineered 
      neuro-vascular co-culture construct, and demonstrate that it exhibits enhanced 
      neurotrophic factor expression, and more complex neuronal morphology. Crucially, 
      by introducing genetically encoded calcium indicators (GECIs) into the 
      co-culture, we are able to monitor functional activity of the neural network, and 
      demonstrate greater activity levels and complexity as a result of the 
      introduction of endothelial cells in the construct. The presence of this enhanced 
      activity could putatively lead to superior integration outcomes. Indeed, 
      leveraging on the ability to monitor the construct's development 
      post-implantation with GECIs, we observe improved integration phenotypes in the 
      spinal cord of mice relative to non-vascularized controls. Our approach provides 
      a new experimental system with functional neural feedback for studying the 
      interplay between vascular and neural development while advancing the 
      optimization of neural implants towards potential clinical applications.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Shor, Erez
AU  - Shor E
AD  - Department of Biomedical Engineering, Technion IIT, Haifa, Israel.
FAU - Merdler, Uri
AU  - Merdler U
AD  - Department of Biomedical Engineering, Technion IIT, Haifa, Israel.
FAU - Brosh, Inbar
AU  - Brosh I
AD  - Department of Biomedical Engineering, Technion IIT, Haifa, Israel.
FAU - Shoham, Shy
AU  - Shoham S
AD  - Department of Biomedical Engineering, Technion IIT, Haifa, Israel. Electronic 
      address: shy@technion.ac.il.
FAU - Levenberg, Shulamit
AU  - Levenberg S
AD  - Department of Biomedical Engineering, Technion IIT, Haifa, Israel. Electronic 
      address: shulamit@bm.technion.ac.il.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180704
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Biocompatible Materials)
SB  - IM
MH  - Animals
MH  - Biocompatible Materials/*chemistry
MH  - Humans
MH  - Mice
MH  - Neovascularization, Physiologic/physiology
MH  - Tissue Engineering/*methods
MH  - Tissue Scaffolds/chemistry
OTO - NOTNLM
OT  - Biomaterials
OT  - Engineered neural implants
OT  - Functional neural activity monitoring
OT  - Induced neural activity
OT  - Neuro-vascular interactions
OT  - Tissue engineering
EDAT- 2018/07/18 06:00
MHDA- 2019/10/01 06:00
CRDT- 2018/07/18 06:00
PHST- 2018/03/29 00:00 [received]
PHST- 2018/06/23 00:00 [revised]
PHST- 2018/07/01 00:00 [accepted]
PHST- 2018/07/18 06:00 [pubmed]
PHST- 2019/10/01 06:00 [medline]
PHST- 2018/07/18 06:00 [entrez]
AID - S0142-9612(18)30470-8 [pii]
AID - 10.1016/j.biomaterials.2018.07.001 [doi]
PST - ppublish
SO  - Biomaterials. 2018 Oct;180:1-11. doi: 10.1016/j.biomaterials.2018.07.001. Epub 
      2018 Jul 4.