Tailoring the subchondral bone phase of a multi-layered osteochondral construct to support bone healing and a cartilage analog

Marionneaux, Alan; Walters, Joshua; Guo, Helena; Mercuri, Jeremy

doi:10.1016/j.actbio.2018.08.009

Cited by 14 publications

(10 citation statements)

References 45 publications

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“…Zonal designs mimicking the vertical organization of cells and matrix in a joint are promising tools to enhance cartilage regeneration. Several studies have shown that not only are such designs technically feasible [17,18] but that they can improve integration into osteochondral defects [14,19,20]. The importance of the calcified cartilage has already been depicted in 1975 [21].…”

Section: Discussionmentioning

confidence: 99%

Treatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs

Bothe

Deubel

Hesse

et al. 2019

IJMS

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Despite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (µCT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O’Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage.

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Section: Discussionmentioning

confidence: 99%

Treatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs

Bothe

Deubel

Hesse

et al. 2019

IJMS

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“…Chitosan has demonstrated potential in cartilage and bone tissue engineering since it can support the expression of ECM proteins in chondrocytes and osteoblasts, and accelerate vascularization to induce intramembranous bone formation. , Although injectable chitosan-based hydrogels and chitosan/bioceramic composited hydrogels are effective strategies to repair small focal cartilage or bone defects, they show little effect on the repair of large osteochondral defects due to mechanical insufficiency. − Multilayered/gradient hydrogels are developed by assembling hydrogels with varying compositions and structures. These can imitate the layered mechanical and biomedical functions of osteochondral tissue. ,− For chitosan-based hydrogels, the mechanical weakness hinders their fabrications to achieve the gradient, osteochondral-mimicking characteristics, and fulfill the load-bearing functions. The chitosan hydrogels prepared from the LiOH/urea solvent system were biocompatible, tough, and robust, which have promising applications in load-bearing tissue engineering, but there have been very limited studies reported in the literature.…”

Section: Discussionmentioning

confidence: 99%

High-Strength, Biomimetic Functional Chitosan-Based Hydrogels for Full-Thickness Osteochondral Defect Repair

Fang

Liao

Zhong

et al. 2022

ACS Biomater. Sci. Eng.

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Fabrication of a hydrogel scaffold for full-thickness osteochondral defect repair remains a grand challenge. Developing layered and multiphasic hydrogels to mimic the intrinsic hierarchical structure of the osteochondral unit is a promising strategy. Chitosan-based hydrogels are widely applied for biomedical applications. However, insufficient mechanical strength and lack of biological cues to restore damaged cartilage and subchondral tissue significantly hinder their application in osteochondral tissue engineering. In this study, a strong and tough, osteochondral-mimicking functional chitosan-based hydrogel (bilayer-gel) with an in situ mineralized, osteoconductive lower layer and a basic fibroblast growth factor (bFGF)-incorporated, chondrogenic inducing upper layer was developed. The obtained bilayer-gel showed a depth-dependent gradient pore structure and composition. The strong double crosslinked hydrogel network and the homogeneous deposition of hydroxyapatite nanoparticles (HAp) at the lower layer provided a compressive strength of up to 2.5 MPa and a compressive strain of up to 40%. In vitro study showed that the bilayer-gel facilitates both chondrogenic differentiation in the upper layer and osteogenic differentiation in the lower layer. In vivo implantation revealed that the bilayer-gel could simultaneously promote hyaline cartilage and subchondral bone formation, thus resulting in an improved osteochondral reconstruction outcome. The present bilayer-gel thus shows great potential for full-thickness osteochondral defect repair.

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“…One of the most important reasons for unsatisfactory cartilage repair has been shown to be an insufficient number of bone mesenchymal stem cells (MSCs) migrating and remaining inside the healing site [43,44]. Increasing the number of MSCs by MSC-derived ECM scaffold or local injection of MSCs has been revealed to promote cartilage regeneration [45][46][47][48]. Because we created, in our study, animal models of a full thickness osteochondral defect in which the articular osseous surface was also involved, the synergistic effect of HA-g-CS implant and moderate-intensity exercise combined together might have lain in increased mobilization and migration of MSCs into the subchondral bone at the injury site and further into the HA-g-CS implant at the cartilage defect.…”

Section: Discussionmentioning

confidence: 99%

HA-g-CS Implant and Moderate-intensity Exercise Stimulate Subchondral Bone Remodeling and Promote Repair of Osteochondral Defects in Mice

Ke¹,

Liu²,

Qin³

et al. 2021

Int. J. Med. Sci.

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Tailoring the subchondral bone phase of a multi-layered osteochondral construct to support bone healing and a cartilage analog

Cited by 14 publications

References 45 publications

Treatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs

Treatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs

High-Strength, Biomimetic Functional Chitosan-Based Hydrogels for Full-Thickness Osteochondral Defect Repair

HA-g-CS Implant and Moderate-intensity Exercise Stimulate Subchondral Bone Remodeling and Promote Repair of Osteochondral Defects in Mice

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