TY - JOUR
T1 - Glycosaminoglycan functionalization of electrospun scaffolds enhances Schwann cell activity
AU - Idini, Michela
AU - Wieringa, Paul
AU - Rocchiccioli, Silvia
AU - Nieddu, Gabriele
AU - Ucciferri, Nadia
AU - Formato, Marilena
AU - Lepedda, Antonio
AU - Moroni, Lorenzo
N1 - Funding Information:
This research project has been made possible with the support of the Dutch Province of Limburg.
Publisher Copyright:
© 2019 Acta Materialia Inc.
PY - 2019/9/15
Y1 - 2019/9/15
N2 - Nerve fibers of the peripheral nervous system (PNS) have a remarkable ability to regenerate up to an almost complete recovery of normal function following a crush or a Sunderland Type II injury. This process is governed by glial cells, known as Schwann cells, through their unique capacity to dedifferentiate into cells that drive the healing process. Despite that many progresses have occurred in restorative medicine and microsurgery, the regenerative process after a severe lesion of a major nerve trunk (e.g., Sunderland Types III-V) is often incomplete and functional recovery is unsatisfactory. In this aspect, it is known that glycosaminoglycans (GAGs) of the extracellular matrix are involved in proliferation, synaptogenesis, neural plasticity, and regeneration of the PNS. Here, we developed poly(caprolactone) (PCL) fibrous scaffolds functionalized with GAGs, which allowed us to assess their influence on the adhesion, proliferation, and differentiation of Schwann cells. We found that both aligned and random fiber scaffolds functionalized with GAGs resulted in increased cell proliferation on day 1. In addition, aligned functionalized scaffolds also resulted in increased GAG presence on day 1, probably because of cell extracellular matrix (ECM) formation and an increased syndecan-4 expression on day 7. A different modification and activation of Schwann cells in the presence of GAG versus no-GAG scaffolds was underlined by proteomic comparative analysis, where a general downregulation of the expression of intracellular/structural and synthetic proteins was shown on day 7 for GAG-functionalized scaffolds with regard to the nonfunctionalized ones. In conclusion, we have shown that GAG-functionalized scaffolds are effective in modulating Schwann cell behavior in terms of adhesion, proliferation, and differentiation and should be considered in strategies to improve PNS repair.Statement of SignificanceNerve fibers functional recovery following a severe trauma of the Peripheral Nervous System (PNS) still represents a huge challenge for neurosurgery nowadays. In this respect, tissue engineering is committed to develop new constructs able to guide Schwann cells by mimicking the natural extracellular matrix environment. To this purpose, we successfully fabricated polycaprolactone (PCL) scaffolds with two well-defined fiber deposition patterns, functionalized with glycosaminoglycans (GAGs) and assessed for their potential as support for Schwann cells adhesion, growth and differentiation, by both classical biochemistry and LC-MS-based proteomic profiling. By this way, we showed that PCL-GAGs scaffolds could represent a promising artificial substrate that closely mimics the recently established pattern of Schwann cells migration into the regenerating nerve and, therefore, it should be considered in strategies to improve PNS repair. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
AB - Nerve fibers of the peripheral nervous system (PNS) have a remarkable ability to regenerate up to an almost complete recovery of normal function following a crush or a Sunderland Type II injury. This process is governed by glial cells, known as Schwann cells, through their unique capacity to dedifferentiate into cells that drive the healing process. Despite that many progresses have occurred in restorative medicine and microsurgery, the regenerative process after a severe lesion of a major nerve trunk (e.g., Sunderland Types III-V) is often incomplete and functional recovery is unsatisfactory. In this aspect, it is known that glycosaminoglycans (GAGs) of the extracellular matrix are involved in proliferation, synaptogenesis, neural plasticity, and regeneration of the PNS. Here, we developed poly(caprolactone) (PCL) fibrous scaffolds functionalized with GAGs, which allowed us to assess their influence on the adhesion, proliferation, and differentiation of Schwann cells. We found that both aligned and random fiber scaffolds functionalized with GAGs resulted in increased cell proliferation on day 1. In addition, aligned functionalized scaffolds also resulted in increased GAG presence on day 1, probably because of cell extracellular matrix (ECM) formation and an increased syndecan-4 expression on day 7. A different modification and activation of Schwann cells in the presence of GAG versus no-GAG scaffolds was underlined by proteomic comparative analysis, where a general downregulation of the expression of intracellular/structural and synthetic proteins was shown on day 7 for GAG-functionalized scaffolds with regard to the nonfunctionalized ones. In conclusion, we have shown that GAG-functionalized scaffolds are effective in modulating Schwann cell behavior in terms of adhesion, proliferation, and differentiation and should be considered in strategies to improve PNS repair.Statement of SignificanceNerve fibers functional recovery following a severe trauma of the Peripheral Nervous System (PNS) still represents a huge challenge for neurosurgery nowadays. In this respect, tissue engineering is committed to develop new constructs able to guide Schwann cells by mimicking the natural extracellular matrix environment. To this purpose, we successfully fabricated polycaprolactone (PCL) scaffolds with two well-defined fiber deposition patterns, functionalized with glycosaminoglycans (GAGs) and assessed for their potential as support for Schwann cells adhesion, growth and differentiation, by both classical biochemistry and LC-MS-based proteomic profiling. By this way, we showed that PCL-GAGs scaffolds could represent a promising artificial substrate that closely mimics the recently established pattern of Schwann cells migration into the regenerating nerve and, therefore, it should be considered in strategies to improve PNS repair. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
KW - Electrospinning
KW - Schwann cells
KW - Neural regeneration
KW - Proteoglycans
KW - PERIPHERAL-NERVE REGENERATION
KW - CHONDROITIN SULFATE
KW - GROWTH-FACTOR
KW - SCIATIC-NERVE
KW - SPINAL-CORD
KW - IN-VITRO
KW - CONDUITS
KW - SYNDECAN-4
KW - GRAFTS
KW - REPAIR
U2 - 10.1016/j.actbio.2019.06.054
DO - 10.1016/j.actbio.2019.06.054
M3 - Article
SN - 1742-7061
VL - 96
SP - 188
EP - 202
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -