Nose-to-Knee Transplantation for Osteochondral Regeneration: A Proof-of-Concept Study in Sheep Employing Ceramic-Hydrogel Osteochondral Grafts
- 1IBEC
Abstract
Osteochondral defects remain a major clinical challenge, frequently progressing to osteoarthritis and ultimately requiring joint replacement. Despite advances in regenerative strategies, current approaches often fail to restore the structural and functional complexity of the osteochondral unit, resulting in poor integration and limited long-term performance. Here, we developed autologous osteochondral grafts combining mechanically mature nasal chondrocyte-derived cartilage with a 3D-printed strontium-hardystonite-gahnite trabecular bone scaffold, which was tested in an osteochondral defect model in sheep. Nasal chondrocytes were encapsulated in a hyaluronan transglutaminase-alginate hydrogel generating hyaline-like cartilage with physiologically relevant compressive properties (1.0 +/- 0.2 MPa) after 6 weeks of in vitro maturation. MicroCT scans of the osteochondral unit were used to design biomimetic trabecular bone scaffolds. Controlled infiltration of the hydrogel into the trabecular pores and subsequent cartilage maturation created a mechanical interlock between cartilage and bone layer, reaching an interfacial shear strength of 201 +/- 42 kPa. The translational potential of this approach was evaluated in a proof-of-concept ovine study. The engineered cartilage remained attached to the bone scaffold for three months following implantation, but osteochondral repair was limited by implant sinking, likely caused by inadequate implant fixation in the defect, resulting in micromotion, synovial fluid infiltration, osteolysis and subsequent bone cyst formation. Together, this work demonstrates the feasibility of engineering mechanically mature autologous osteochondral grafts while identifying subchondral bone integration as the primary bottleneck limiting successful osteochondral regeneration and future clinical translation.
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BibTeX
@misc{fisch2026nosetoknee,
title = {{Nose-to-Knee Transplantation for Osteochondral Regeneration: A Proof-of-Concept Study in Sheep Employing Ceramic-Hydrogel Osteochondral Grafts}},
author = {P. Fisch and I. Roohani and S. Ponta and S. Chen and N. Alibert and D. Fercher and K. Klein and B. von Rechenberg and M. Zenobi-Wong and S. Darwiche and H. Zreiqat and A. Puiggali Jou},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.757945},
url = {https://www.biorxiv.org/content/10.64898/2026.10.09.757945v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Nose-to-Knee Transplantation for Osteochondral Regeneration: A Proof-of-Concept Study in Sheep Employing Ceramic-Hydrogel Osteochondral Grafts
AU - P. Fisch
AU - I. Roohani
AU - S. Ponta
AU - S. Chen
AU - N. Alibert
AU - D. Fercher
AU - K. Klein
AU - B. von Rechenberg
AU - M. Zenobi-Wong
AU - S. Darwiche
AU - H. Zreiqat
AU - A. Puiggali Jou
PY - 2026
DA - 2026/10/09
PB - bioRxiv
DO - 10.64898/2026.10.09.757945
UR - https://www.biorxiv.org/content/10.64898/2026.10.09.757945v1
AB - Osteochondral defects remain a major clinical challenge, frequently progressing to osteoarthritis and ultimately requiring joint replacement. Despite advances in regenerative strategies, current approaches often fail to restore the structural and functional complexity of the osteochondral unit, resulting in poor integration and limited long-term performance. Here, we developed autologous osteochondral grafts combining mechanically mature nasal chondrocyte-derived cartilage with a 3D-printed strontium-hardystonite-gahnite trabecular bone scaffold, which was tested in an osteochondral defect model in sheep. Nasal chondrocytes were encapsulated in a hyaluronan transglutaminase-alginate hydrogel generating hyaline-like cartilage with physiologically relevant compressive properties (1.0 +/- 0.2 MPa) after 6 weeks of in vitro maturation. MicroCT scans of the osteochondral unit were used to design biomimetic trabecular bone scaffolds. Controlled infiltration of the hydrogel into the trabecular pores and subsequent cartilage maturation created a mechanical interlock between cartilage and bone layer, reaching an interfacial shear strength of 201 +/- 42 kPa. The translational potential of this approach was evaluated in a proof-of-concept ovine study. The engineered cartilage remained attached to the bone scaffold for three months following implantation, but osteochondral repair was limited by implant sinking, likely caused by inadequate implant fixation in the defect, resulting in micromotion, synovial fluid infiltration, osteolysis and subsequent bone cyst formation. Together, this work demonstrates the feasibility of engineering mechanically mature autologous osteochondral grafts while identifying subchondral bone integration as the primary bottleneck limiting successful osteochondral regeneration and future clinical translation.
ER -