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Manufacturing of Human Tissues as off-the-Shelf Grafts Programmed to Induce Regeneration

Pigeot, Sébastien ; Klein, Thibaut ; Gullotta, Fabiana ; Dupard, Steven J. LU ; Garcia Garcia, Alejandro LU ; García-García, Andres ; Prithiviraj, Sujeethkumar LU ; Lorenzo, Pilar LU ; Filippi, Miriam and Jaquiery, Claude , et al. (2021) In Advanced Materials 33(43).
Abstract

Design criteria for tissue-engineered materials in regenerative medicine include robust biological effectiveness, off-the-shelf availability, and scalable manufacturing under standardized conditions. For bone repair, existing strategies rely on primary autologous cells, associated with unpredictable performance, limited availability and complex logistic. Here, a conceptual shift based on the manufacturing of devitalized human hypertrophic cartilage (HyC), as cell-free material inducing bone formation by recapitulating the developmental process of endochondral ossification, is reported. The strategy relies on a customized human mesenchymal line expressing bone morphogenetic protein-2 (BMP-2), critically required for robust chondrogenesis... (More)

Design criteria for tissue-engineered materials in regenerative medicine include robust biological effectiveness, off-the-shelf availability, and scalable manufacturing under standardized conditions. For bone repair, existing strategies rely on primary autologous cells, associated with unpredictable performance, limited availability and complex logistic. Here, a conceptual shift based on the manufacturing of devitalized human hypertrophic cartilage (HyC), as cell-free material inducing bone formation by recapitulating the developmental process of endochondral ossification, is reported. The strategy relies on a customized human mesenchymal line expressing bone morphogenetic protein-2 (BMP-2), critically required for robust chondrogenesis and concomitant extracellular matrix (ECM) enrichment. Following apoptosis-driven devitalization, lyophilization, and storage, the resulting off-the-shelf cartilage tissue exhibits unprecedented osteoinductive properties, unmatched by synthetic delivery of BMP-2 or by living engineered grafts. Scalability and pre-clinical efficacy are demonstrated by bioreactor-based production and subsequent orthotopic assessment. The findings exemplify the broader paradigm of programming human cell lines as biological factory units to engineer customized ECMs, designed to activate specific regenerative processes.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
BMP2, bone grafts, endochondral ossification, extracellular matrices, regenerative medicine
in
Advanced Materials
volume
33
issue
43
article number
2103737
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85114312808
  • pmid:34486186
ISSN
0935-9648
DOI
10.1002/adma.202103737
language
English
LU publication?
yes
id
625ada2c-4d1f-4814-9e7f-448b0dd40772
date added to LUP
2021-10-05 12:38:26
date last changed
2025-01-26 16:31:32
@article{625ada2c-4d1f-4814-9e7f-448b0dd40772,
  abstract     = {{<p>Design criteria for tissue-engineered materials in regenerative medicine include robust biological effectiveness, off-the-shelf availability, and scalable manufacturing under standardized conditions. For bone repair, existing strategies rely on primary autologous cells, associated with unpredictable performance, limited availability and complex logistic. Here, a conceptual shift based on the manufacturing of devitalized human hypertrophic cartilage (HyC), as cell-free material inducing bone formation by recapitulating the developmental process of endochondral ossification, is reported. The strategy relies on a customized human mesenchymal line expressing bone morphogenetic protein-2 (BMP-2), critically required for robust chondrogenesis and concomitant extracellular matrix (ECM) enrichment. Following apoptosis-driven devitalization, lyophilization, and storage, the resulting off-the-shelf cartilage tissue exhibits unprecedented osteoinductive properties, unmatched by synthetic delivery of BMP-2 or by living engineered grafts. Scalability and pre-clinical efficacy are demonstrated by bioreactor-based production and subsequent orthotopic assessment. The findings exemplify the broader paradigm of programming human cell lines as biological factory units to engineer customized ECMs, designed to activate specific regenerative processes.</p>}},
  author       = {{Pigeot, Sébastien and Klein, Thibaut and Gullotta, Fabiana and Dupard, Steven J. and Garcia Garcia, Alejandro and García-García, Andres and Prithiviraj, Sujeethkumar and Lorenzo, Pilar and Filippi, Miriam and Jaquiery, Claude and Kouba, Loraine and Asnaghi, M. Adelaide and Raina, Deepak Bushan and Dasen, Boris and Isaksson, Hanna and Önnerfjord, Patrik and Tägil, Magnus and Bondanza, Attilio and Martin, Ivan and Bourgine, Paul E.}},
  issn         = {{0935-9648}},
  keywords     = {{BMP2; bone grafts; endochondral ossification; extracellular matrices; regenerative medicine}},
  language     = {{eng}},
  number       = {{43}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Advanced Materials}},
  title        = {{Manufacturing of Human Tissues as off-the-Shelf Grafts Programmed to Induce Regeneration}},
  url          = {{http://dx.doi.org/10.1002/adma.202103737}},
  doi          = {{10.1002/adma.202103737}},
  volume       = {{33}},
  year         = {{2021}},
}