TY - JOUR
T1 - 3D bioprinting of multilayered scaffolds with spatially differentiated ADMSCs for rotator cuff tendon-to-bone interface regeneration
AU - Jiang, Xiping
AU - Kong, Yunfan
AU - Kuss, Mitchell
AU - Weisenburger, Joel
AU - Haider, Hani
AU - Harms, Robert
AU - Shi, Wen
AU - Liu, Bo
AU - Xue, Wen
AU - Dong, Jianghu
AU - Xie, Jingwei
AU - Streubel, Philipp
AU - Duan, Bin
N1 - Funding Information:
This work has been supported by National Institute of Health (NIH R01 AR073225) for B.D. and P.S. X.J is partially supported by the China Scholarship Council and UNMC fellowship. We want to thank the comparative medicine group from UNMC for the help with the rabbit animal surgeries, especially Kristin Leland, Wendy Schwendeman, and Rebecca Schertz. We would like to thank Dr. Yutong Liu and Dr. Lirong Xu from UNMC for the aid with MRI imaging, the Tissue Science Core Facility of UNMC for the histological staining, Dr. Wenlong Li from University of Nebraska-Lincoln for the help with in vitro mechanical testing. We also wish to thank UNMC Flow Cytometry Core facility for technical support. The UNMC Flow Cytometry Research Facility is administrated through the Office of the Vice Chancellor for Research and supported by state funds from the Nebraska Research Initiative (NRI) and The Fred and Pamela Buffett Cancer Center's National Cancer Institute Cancer Support Grant. Major instrumentation has been provided by the Office of the Vice Chancellor for Research, The University of Nebraska Foundation, the Nebraska Banker's Fund, and by the NIH–NCRR Shared Instrument Program.
Funding Information:
This work has been supported by National Institute of Health (NIH R01 AR073225) for B.D. and P.S. X.J is partially supported by the China Scholarship Council and UNMC fellowship. We want to thank the comparative medicine group from UNMC for the help with the rabbit animal surgeries, especially Kristin Leland, Wendy Schwendeman, and Rebecca Schertz. We would like to thank Dr. Yutong Liu and Dr. Lirong Xu from UNMC for the aid with MRI imaging, the Tissue Science Core Facility of UNMC for the histological staining, Dr. Wenlong Li from University of Nebraska-Lincoln for the help with in vitro mechanical testing. We also wish to thank UNMC Flow Cytometry Core facility for technical support. The UNMC Flow Cytometry Research Facility is administrated through the Office of the Vice Chancellor for Research and supported by state funds from the Nebraska Research Initiative (NRI) and The Fred and Pamela Buffett Cancer Center's National Cancer Institute Cancer Support Grant. Major instrumentation has been provided by the Office of the Vice Chancellor for Research, The University of Nebraska Foundation, the Nebraska Banker's Fund, and by the NIH NCRR Shared Instrument Program.
Publisher Copyright:
© 2022
PY - 2022/6
Y1 - 2022/6
N2 - Regeneration of the gradient structure of the tendon-to-bone interface is still a significant clinical challenge. This study reports a novel therapeutic method combining three-dimensional (3D) bioprinting and melt electrospinning writing techniques to regenerate a functional tendon-to-bone interface. We generated biomimetic multilayered scaffolds with 3D-bioprinted pre-differentiated autologous adipose-derived mesenchymal stem cells (ADMSC), which recapitulated compositional and cellular structures of the interface. The hydrogel-based bioinks offered high cell viability and proliferative capability for rabbit ADMSCs. The hydrogels with pre-differentiated (into tenogenic, chondrogenic, and osteogenic lineages) or undifferentiated rabbit ADMSCs were 3D-bioprinted into zonal-specific constructs to mimic the structure of the tendon-to-bone interface. These scaffolds were tested in a rabbit rotator cuff injury model and the histological, radiological, and biomechanical changes were analyzed. The in vivo studies demonstrated that the scaffold with spatially differentiated autologous ADMSCs had a superior histological score and improved collagen organization when compared to acellular scaffolds and similar T2 value as the normal interface tissue. The biomechanical characterization demonstrated that the application of multilayered scaffolds improved the biomechanical properties of the tendon-to-bone interface at 12 weeks after rotator cuff reconstruction surgery, but the incorporation of autologous ADMSCs within the multilayered scaffolds showed a limited contribution. Thus, our work provides a 3D-bioprinting-based strategy with the application of autologous ADMSCs to reconstruct massive rotator cuff tendon tears.
AB - Regeneration of the gradient structure of the tendon-to-bone interface is still a significant clinical challenge. This study reports a novel therapeutic method combining three-dimensional (3D) bioprinting and melt electrospinning writing techniques to regenerate a functional tendon-to-bone interface. We generated biomimetic multilayered scaffolds with 3D-bioprinted pre-differentiated autologous adipose-derived mesenchymal stem cells (ADMSC), which recapitulated compositional and cellular structures of the interface. The hydrogel-based bioinks offered high cell viability and proliferative capability for rabbit ADMSCs. The hydrogels with pre-differentiated (into tenogenic, chondrogenic, and osteogenic lineages) or undifferentiated rabbit ADMSCs were 3D-bioprinted into zonal-specific constructs to mimic the structure of the tendon-to-bone interface. These scaffolds were tested in a rabbit rotator cuff injury model and the histological, radiological, and biomechanical changes were analyzed. The in vivo studies demonstrated that the scaffold with spatially differentiated autologous ADMSCs had a superior histological score and improved collagen organization when compared to acellular scaffolds and similar T2 value as the normal interface tissue. The biomechanical characterization demonstrated that the application of multilayered scaffolds improved the biomechanical properties of the tendon-to-bone interface at 12 weeks after rotator cuff reconstruction surgery, but the incorporation of autologous ADMSCs within the multilayered scaffolds showed a limited contribution. Thus, our work provides a 3D-bioprinting-based strategy with the application of autologous ADMSCs to reconstruct massive rotator cuff tendon tears.
KW - Adipose-derived mesenchymal stem cells
KW - Direct writing
KW - Tendon tissue engineering
KW - Tendon-to-bone interface
UR - http://www.scopus.com/inward/record.url?scp=85129945733&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85129945733&partnerID=8YFLogxK
U2 - 10.1016/j.apmt.2022.101510
DO - 10.1016/j.apmt.2022.101510
M3 - Article
AN - SCOPUS:85129945733
SN - 2352-9407
VL - 27
JO - Applied Materials Today
JF - Applied Materials Today
M1 - 101510
ER -