Injectable osteogenic microtissues containing mesenchymal stromal cells conformally fill and repair critical-size defects

Ramkumar T. Annamalai; Xiaowei Hong; Nicholas G. Schott; Gopinath Tiruchinapally; Benjamin Levi; Jan P. Stegemann

doi:10.1016/j.biomaterials.2019.04.001

Injectable osteogenic microtissues containing mesenchymal stromal cells conformally fill and repair critical-size defects

Ramkumar T. Annamalai, Xiaowei Hong, Nicholas G. Schott, Gopinath Tiruchinapally, Benjamin Levi, Jan P. Stegemann

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

67 Scopus citations

Abstract

Repair of complex fractures with bone loss requires a potent, space-filling intervention to promote regeneration of bone. We present a biomaterials-based strategy combining mesenchymal stromal cells (MSC) with a chitosan-collagen matrix to form modular microtissues designed for delivery through a needle to conformally fill cavital defects. Implantation of microtissues into a calvarial defect in the mouse showed that osteogenically pre-differentiated MSC resulted in complete bridging of the cavity, while undifferentiated MSC produced mineralized tissue only in apposition to native bone. Decreasing the implant volume reduced bone regeneration, while increasing the MSC concentration also attenuated bone formation, suggesting that the cell-matrix ratio is important in achieving a robust response. Conformal filling of the defect with microtissues in a carrier gel resulted in complete healing. Taken together, these results show that modular microtissues can be used to augment the differentiated function of MSC and provide an extracellular environment that potentiates bone repair.

Original language	English
Pages (from-to)	32-44
Number of pages	13
Journal	Biomaterials
Volume	208
DOIs	https://doi.org/10.1016/j.biomaterials.2019.04.001
State	Published - Jul 2019

Bibliographical note

Funding Information:
Research reported in this publication was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases ( R01AR062636 to JPS and R01AR071379 to BL), the National Institute of Dental and Craniofacial Research ( R01DE026630 , to JPS). BL is supported by funding from the National Institute of General Medical Sciences ( K08GM109105-0 and R01GM123069 ), American College of Surgeons Clowes Award and the International FOP Association . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2019 Elsevier Ltd

Keywords

Bone regeneration
Chitosan and collagen
Critical size defect
Mesenchymal stromal cells
Microtissues
Non-invasive delivery

ASJC Scopus subject areas

Bioengineering
Ceramics and Composites
Biophysics
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2019.04.001

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title = "Injectable osteogenic microtissues containing mesenchymal stromal cells conformally fill and repair critical-size defects",

abstract = "Repair of complex fractures with bone loss requires a potent, space-filling intervention to promote regeneration of bone. We present a biomaterials-based strategy combining mesenchymal stromal cells (MSC) with a chitosan-collagen matrix to form modular microtissues designed for delivery through a needle to conformally fill cavital defects. Implantation of microtissues into a calvarial defect in the mouse showed that osteogenically pre-differentiated MSC resulted in complete bridging of the cavity, while undifferentiated MSC produced mineralized tissue only in apposition to native bone. Decreasing the implant volume reduced bone regeneration, while increasing the MSC concentration also attenuated bone formation, suggesting that the cell-matrix ratio is important in achieving a robust response. Conformal filling of the defect with microtissues in a carrier gel resulted in complete healing. Taken together, these results show that modular microtissues can be used to augment the differentiated function of MSC and provide an extracellular environment that potentiates bone repair.",

keywords = "Bone regeneration, Chitosan and collagen, Critical size defect, Mesenchymal stromal cells, Microtissues, Non-invasive delivery",

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note = "Funding Information: Research reported in this publication was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases ( R01AR062636 to JPS and R01AR071379 to BL), the National Institute of Dental and Craniofacial Research ( R01DE026630 , to JPS). BL is supported by funding from the National Institute of General Medical Sciences ( K08GM109105-0 and R01GM123069 ), American College of Surgeons Clowes Award and the International FOP Association . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

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AU - Levi, Benjamin

AU - Stegemann, Jan P.

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N2 - Repair of complex fractures with bone loss requires a potent, space-filling intervention to promote regeneration of bone. We present a biomaterials-based strategy combining mesenchymal stromal cells (MSC) with a chitosan-collagen matrix to form modular microtissues designed for delivery through a needle to conformally fill cavital defects. Implantation of microtissues into a calvarial defect in the mouse showed that osteogenically pre-differentiated MSC resulted in complete bridging of the cavity, while undifferentiated MSC produced mineralized tissue only in apposition to native bone. Decreasing the implant volume reduced bone regeneration, while increasing the MSC concentration also attenuated bone formation, suggesting that the cell-matrix ratio is important in achieving a robust response. Conformal filling of the defect with microtissues in a carrier gel resulted in complete healing. Taken together, these results show that modular microtissues can be used to augment the differentiated function of MSC and provide an extracellular environment that potentiates bone repair.

AB - Repair of complex fractures with bone loss requires a potent, space-filling intervention to promote regeneration of bone. We present a biomaterials-based strategy combining mesenchymal stromal cells (MSC) with a chitosan-collagen matrix to form modular microtissues designed for delivery through a needle to conformally fill cavital defects. Implantation of microtissues into a calvarial defect in the mouse showed that osteogenically pre-differentiated MSC resulted in complete bridging of the cavity, while undifferentiated MSC produced mineralized tissue only in apposition to native bone. Decreasing the implant volume reduced bone regeneration, while increasing the MSC concentration also attenuated bone formation, suggesting that the cell-matrix ratio is important in achieving a robust response. Conformal filling of the defect with microtissues in a carrier gel resulted in complete healing. Taken together, these results show that modular microtissues can be used to augment the differentiated function of MSC and provide an extracellular environment that potentiates bone repair.

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Injectable osteogenic microtissues containing mesenchymal stromal cells conformally fill and repair critical-size defects

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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