J Lam1, S Lu1, E J Lee1, J E Trachtenberg1, V V Meretoja1, R L Dahlin1, J J J P van den Beucken2, Y Tabata3, M E Wong4, J A Jansen2, A G Mikos5, F K Kasper6. 1. Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA. 2. Department of Biomaterials, Radboud umc, Nijmegen, The Netherlands. 3. Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan. 4. Department of Surgery, Division of Oral and Maxillofacial Surgery, The University of Texas School of Dentistry, Houston, TX, USA. 5. Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA. Electronic address: mikos@rice.edu. 6. Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, USA. Electronic address: kasper@rice.edu.
Abstract
OBJECTIVE: To investigate the ability of cell-laden bilayered hydrogels encapsulating chondrogenically and osteogenically (OS) pre-differentiated mesenchymal stem cells (MSCs) to effect osteochondral defect repair in a rabbit model. By varying the period of chondrogenic pre-differentiation from 7 (CG7) to 14 days (CG14), the effect of chondrogenic differentiation stage on osteochondral tissue repair was also investigated. METHODS: Rabbit MSCs were subjected to either chondrogenic or osteogenic pre-differentiation, encapsulated within respective chondral/subchondral layers of a bilayered hydrogel construct, and then implanted into femoral condyle osteochondral defects. Rabbits were randomized into one of four groups (MSC/MSC, MSC/OS, CG7/OS, and CG14/OS; chondral/subchondral) and received two similar constructs bilaterally. Defects were evaluated after 12 weeks. RESULTS: All groups exhibited similar overall neo-tissue filling. The delivery of OS cells when compared to undifferentiated MSCs in the subchondral construct layer resulted in improvements in neo-cartilage thickness and regularity. However, the addition of CG cells in the chondral layer, with OS cells in the subchondral layer, did not augment tissue repair as influenced by the latter when compared to the control. Instead, CG7/OS implants resulted in more irregular neo-tissue surfaces when compared to MSC/OS implants. Notably, the delivery of CG7 cells, when compared to CG14 cells, with OS cells stimulated morphologically superior cartilage repair. However, neither osteogenic nor chondrogenic pre-differentiation affected detectable changes in subchondral tissue repair. CONCLUSIONS: Cartilage regeneration in osteochondral defects can be enhanced by MSCs that are chondrogenically and osteogenically pre-differentiated prior to implantation. Longer chondrogenic pre-differentiation periods, however, lead to diminished cartilage repair.
OBJECTIVE: To investigate the ability of cell-laden bilayered hydrogels encapsulating chondrogenically and osteogenically (OS) pre-differentiated mesenchymal stem cells (MSCs) to effect osteochondral defect repair in a rabbit model. By varying the period of chondrogenic pre-differentiation from 7 (CG7) to 14 days (CG14), the effect of chondrogenic differentiation stage on osteochondral tissue repair was also investigated. METHODS:Rabbit MSCs were subjected to either chondrogenic or osteogenic pre-differentiation, encapsulated within respective chondral/subchondral layers of a bilayered hydrogel construct, and then implanted into femoral condyle osteochondral defects. Rabbits were randomized into one of four groups (MSC/MSC, MSC/OS, CG7/OS, and CG14/OS; chondral/subchondral) and received two similar constructs bilaterally. Defects were evaluated after 12 weeks. RESULTS: All groups exhibited similar overall neo-tissue filling. The delivery of OS cells when compared to undifferentiated MSCs in the subchondral construct layer resulted in improvements in neo-cartilage thickness and regularity. However, the addition of CG cells in the chondral layer, with OS cells in the subchondral layer, did not augment tissue repair as influenced by the latter when compared to the control. Instead, CG7/OS implants resulted in more irregular neo-tissue surfaces when compared to MSC/OS implants. Notably, the delivery of CG7 cells, when compared to CG14 cells, with OS cells stimulated morphologically superior cartilage repair. However, neither osteogenic nor chondrogenic pre-differentiation affected detectable changes in subchondral tissue repair. CONCLUSIONS:Cartilage regeneration in osteochondral defects can be enhanced by MSCs that are chondrogenically and osteogenically pre-differentiated prior to implantation. Longer chondrogenic pre-differentiation periods, however, lead to diminished cartilage repair.
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Authors: Jason L Guo; Yu Seon Kim; Gerry L Koons; Johnny Lam; Adam M Navara; Sergio Barrios; Virginia Y Xie; Emma Watson; Brandon T Smith; Hannah A Pearce; Elysse A Orchard; Jeroen J J P van den Beucken; John A Jansen; Mark E Wong; Antonios G Mikos Journal: Acta Biomater Date: 2021-04-27 Impact factor: 10.633