TY - JOUR
T1 - Concentration-dependent rheological properties of ECM hydrogel for intracerebral delivery to a stroke cavity
AU - Massensini, Andre R.
AU - Ghuman, Harmanvir
AU - Saldin, Lindsey T.
AU - Medberry, Christopher J.
AU - Keane, Timothy J.
AU - Nicholls, Francesca J.
AU - Velankar, Sachin S.
AU - Badylak, Stephen F.
AU - Modo, Michel
N1 - Funding Information:
This study was funded by a seed grant from the Department of Health of the Commonwealth of Pennsylvania ( 4100061184 ) and the National Institute for Neurological Disease and Stroke and the National Institute for Biomedical Imaging and Bioengineering ( R01EB016629 ). ARM was supported by a Fellowship from CAPES Foundation, Brazil . CJM and LTS were partially supported by a NIH-NHLBI training grant ( T32-EB001026 , 2T32-EB001026-11 , respectively). TJK was supported by the National Science Foundation Graduate Research Fellowship ( DGE-1247842 ). SFB and MM gratefully acknowledge support from Vertex Pharmaceuticals . SSV acknowledges partial support from NSF-CMMI ( 1434674 ). We thank Dr Hiro Fukuda and Alex Poplawsky with their assistance to measure intracranial pressure and Dr Wen Ling for setting up the MRI scanning.
Publisher Copyright:
© 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
PY - 2015/11
Y1 - 2015/11
N2 - Biomaterials composed of mammalian extracellular matrix (ECM) promote constructive tissue remodeling with minimal scar tissue formation in many anatomical sites. However, the optimal shape and form of ECM scaffold for each clinical application can vary markedly. ECM hydrogels have been shown to promote chemotaxis and differentiation of neuronal stem cells, but minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form. These ECM materials can be manufactured to exist in fluid phase at room temperature, while forming hydrogels at body temperature in a concentration-dependent fashion. Implantation into the lesion cavity after a stroke could hence provide a means to support endogenous repair mechanisms. Herein, we characterize the rheological properties of an ECM hydrogel composed of urinary bladder matrix (UBM) that influence its delivery and in vivo interaction with host tissue. There was a notable concentration-dependence in viscosity, stiffness, and elasticity; all characteristics important for minimally invasive intracerebral delivery. An efficient MRI-guided injection with drainage of fluid from the cavity is described to assess in situ hydrogel formation and ECM retention at different concentrations (0, 1, 2, 3, 4, and 8 mg/mL). Only ECM concentrations >3 mg/mL gelled within the stroke cavity. Lower concentrations were not retained within the cavity, but extensive permeation of the liquid phase ECM into the peri-infarct area was evident. The concentration of ECM hydrogel is hence an important factor affecting gelation, host-biomaterial interface, as well intra-lesion distribution. Statement of Significance Extracellular matrix (ECM) hydrogel promotes constructive tissue remodeling in many tissues. Minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form that exists in fluid phase at room temperature, while forming hydrogels at body temperature in a concentration-dependent fashion. We here report the rheological characterization of an injectable ECM hydrogel and its concentration-dependent delivery into a lesion cavity formed after a stroke based on MRI-guidance. The concentration of ECM determined its retention within the cavity or permeation into tissue and hence influenced its interaction with the host brain. This study demonstrates the importance of understanding the structure-function relationship of biomaterials to guide particular clinical applications.
AB - Biomaterials composed of mammalian extracellular matrix (ECM) promote constructive tissue remodeling with minimal scar tissue formation in many anatomical sites. However, the optimal shape and form of ECM scaffold for each clinical application can vary markedly. ECM hydrogels have been shown to promote chemotaxis and differentiation of neuronal stem cells, but minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form. These ECM materials can be manufactured to exist in fluid phase at room temperature, while forming hydrogels at body temperature in a concentration-dependent fashion. Implantation into the lesion cavity after a stroke could hence provide a means to support endogenous repair mechanisms. Herein, we characterize the rheological properties of an ECM hydrogel composed of urinary bladder matrix (UBM) that influence its delivery and in vivo interaction with host tissue. There was a notable concentration-dependence in viscosity, stiffness, and elasticity; all characteristics important for minimally invasive intracerebral delivery. An efficient MRI-guided injection with drainage of fluid from the cavity is described to assess in situ hydrogel formation and ECM retention at different concentrations (0, 1, 2, 3, 4, and 8 mg/mL). Only ECM concentrations >3 mg/mL gelled within the stroke cavity. Lower concentrations were not retained within the cavity, but extensive permeation of the liquid phase ECM into the peri-infarct area was evident. The concentration of ECM hydrogel is hence an important factor affecting gelation, host-biomaterial interface, as well intra-lesion distribution. Statement of Significance Extracellular matrix (ECM) hydrogel promotes constructive tissue remodeling in many tissues. Minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form that exists in fluid phase at room temperature, while forming hydrogels at body temperature in a concentration-dependent fashion. We here report the rheological characterization of an injectable ECM hydrogel and its concentration-dependent delivery into a lesion cavity formed after a stroke based on MRI-guidance. The concentration of ECM determined its retention within the cavity or permeation into tissue and hence influenced its interaction with the host brain. This study demonstrates the importance of understanding the structure-function relationship of biomaterials to guide particular clinical applications.
KW - Biomaterial
KW - Brain
KW - Delivery
KW - Extracellular matrix
KW - Injection
KW - Magnetic resonance imaging
KW - Stereotactic
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=84944277543&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2015.08.040
DO - 10.1016/j.actbio.2015.08.040
M3 - Article
C2 - 26318805
AN - SCOPUS:84944277543
SN - 1742-7061
VL - 27
SP - 116
EP - 130
JO - Acta Biomaterialia
JF - Acta Biomaterialia
ER -