Manufacturing of Human Tissues as off-the-Shelf Grafts Programmed to Induce Regeneration
(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.
(Less)
- author
- 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
; Jaquiery, Claude
; Kouba, Loraine
; Asnaghi, M. Adelaide
; Raina, Deepak Bushan
LU
; Dasen, Boris
; Isaksson, Hanna
LU
; Önnerfjord, Patrik
LU
; Tägil, Magnus
LU
; Bondanza, Attilio
; Martin, Ivan
and Bourgine, Paul E.
LU
(Less) - organization
-
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Stem Cell Center
- WCMM-Wallenberg Centre for Molecular Medicine
- Rheumatology (research group)
- Department of Clinical Sciences, Lund
- Molecular Skeletal Biology (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Orthopaedics (Lund)
- Rheumatology
- Department of Biomedical Engineering
- publishing date
- 2021
- 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
- 2024-04-20 12:21:23
@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}},
}