TY - JOUR
T1 - A multilayered scaffold for regeneration of smooth muscle and connective tissue layers
AU - Garrison, Carly M.
AU - Singh-Varma, Anya
AU - Pastino, Alexandra K.
AU - Steele, Joseph A.M.
AU - Kohn, Joachim
AU - Murthy, N. Sanjeeva
AU - Schwarzbauer, Jean E.
N1 - Funding Information:
National Institute of Arthritis and Musculoskeletal and Skin Diseases, Grant/Award Number: R01 AR 073236; National Institute of Biomedical Imaging and Bioengineering, Grant/Award Number: P4 EB001046; National Institute of General Medical Sciences, Grant/Award Number: NIH T32 GM007388; New Jersey Commission on Cancer Research (NJCCR), Grant/Award Number: DFHS18PPC041 Funding information
Funding Information:
The authors are grateful Dr. Gary Laevsky, director of the Molecular Biology Confocal Microscopy Core Facility, a Nikon Center of Excellence, for his technical assistance and members of the Schwarzbauer lab for insightful discussions. The authors also thank Dr. Victor Koteliansky for kindly supplying WKY3M22 SMCs. The authors gratefully acknowledge support for this research from the National Institutes of Health to RESBIO—The National Resource for Polymeric Biomaterials (P4 EB001046) (to J. K.) and R01 AR 073236 (to J. E. S.). C. M. G. was supported by the New Jersey Commission on Cancer Research (NJCCR) DFHS18PPC041 predoctoral fellowship and NIH T32 GM007388 predoctoral training grant to the Department of Molecular Biology at Princeton University.
Publisher Copyright:
© 2020 Wiley Periodicals LLC.
PY - 2021/5
Y1 - 2021/5
N2 - Tissue regeneration often requires recruitment of different cell types and rebuilding of two or more tissue layers to restore function. Here, we describe the creation of a novel multilayered scaffold with distinct fiber organizations—aligned to unaligned and dense to porous—to template common architectures found in adjacent tissue layers. Electrospun scaffolds were fabricated using a biodegradable, tyrosine-derived terpolymer, yielding densely-packed, aligned fibers that transition into randomly-oriented fibers of increasing diameter and porosity. We demonstrate that differently-oriented scaffold fibers direct cell and extracellular matrix (ECM) organization, and that scaffold fibers and ECM protein networks are maintained after decellularization. Smooth muscle and connective tissue layers are frequently adjacent in vivo; we show that within a single scaffold, the architecture supports alignment of contractile smooth muscle cells and deposition by fibroblasts of a meshwork of ECM fibrils. We rolled a flat scaffold into a tubular construct and, after culture, showed cell viability, orientation, and tissue-specific protein expression in the tube were similar to the flat-sheet scaffold. This scaffold design not only has translational potential for reparation of flat and tubular tissue layers but can also be customized for alternative applications by introducing two or more cell types in different combinations.
AB - Tissue regeneration often requires recruitment of different cell types and rebuilding of two or more tissue layers to restore function. Here, we describe the creation of a novel multilayered scaffold with distinct fiber organizations—aligned to unaligned and dense to porous—to template common architectures found in adjacent tissue layers. Electrospun scaffolds were fabricated using a biodegradable, tyrosine-derived terpolymer, yielding densely-packed, aligned fibers that transition into randomly-oriented fibers of increasing diameter and porosity. We demonstrate that differently-oriented scaffold fibers direct cell and extracellular matrix (ECM) organization, and that scaffold fibers and ECM protein networks are maintained after decellularization. Smooth muscle and connective tissue layers are frequently adjacent in vivo; we show that within a single scaffold, the architecture supports alignment of contractile smooth muscle cells and deposition by fibroblasts of a meshwork of ECM fibrils. We rolled a flat scaffold into a tubular construct and, after culture, showed cell viability, orientation, and tissue-specific protein expression in the tube were similar to the flat-sheet scaffold. This scaffold design not only has translational potential for reparation of flat and tubular tissue layers but can also be customized for alternative applications by introducing two or more cell types in different combinations.
KW - complex tissue regeneration
KW - extracellular matrix (ECM)
KW - multilayered electrospun scaffolds
KW - synthetic polymer
KW - tubular scaffold
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U2 - 10.1002/jbm.a.37058
DO - 10.1002/jbm.a.37058
M3 - Article
C2 - 32654327
AN - SCOPUS:85089397352
SN - 1549-3296
VL - 109
SP - 733
EP - 744
JO - Journal of Biomedical Materials Research - Part A
JF - Journal of Biomedical Materials Research - Part A
IS - 5
ER -