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

Sébastien Pigeot, Thibaut Klein, Fabiana Gullotta, Steven J. Dupard, Alejandro Garcia Garcia, Andres García-García, Sujeethkumar Prithiviraj, Pilar Lorenzo, Miriam Filippi, Claude Jaquiery, Loraine Kouba, M. Adelaide Asnaghi, Deepak Bushan Raina, Boris Dasen, Hanna Isaksson, Patrik Önnerfjord, Magnus Tägil, Attilio Bondanza, Ivan Martin, Paul E. Bourgine

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number2103737
JournalAdvanced Materials
Issue number43
Early online date2021
Publication statusPublished - 2021

Subject classification (UKÄ)

  • Biomaterials Science

Free keywords

  • BMP2
  • bone grafts
  • endochondral ossification
  • extracellular matrices
  • regenerative medicine


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