High-efficient engineering of osteo-callus organoids for rapid bone regeneration within one month

Xie, Chang; Liang, Renjie; Ye, Jinchun; Peng, Zhi; Sun, Heng; Zhu, Qiuwen; Shen, Xiaohui; Hong, Yi; Wu, Hongwei; Sun, Wei; Yao, Xudong; Li, Jiajin; Zhang, Shufang; Zhang, Xianzhu; Ouyang, Hongwei

doi:10.1016/j.biomaterials.2022.121741

Cited by 68 publications

(55 citation statements)

References 47 publications

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“…However, there was no significant difference in the micro‐CT related parameters (BV/TV, Tb.N, Tb.Sp, Tb.Th). It might be that the subchondral bone generated by endochondral ossification [ 31 ] was more in line with the natural bone generation mode to achieve better repair of cartilage tissue. What is more, the C‐K/O‐TK group exhibited a uniform transitional region (blue and red) between the blue‐stained cartilage layer and the red‐stained bone area, indicating the reconstruction of the calcified cartilage interface (Figure 7C).…”

Section: Resultsmentioning

confidence: 99%

A One‐Stone‐Two‐Birds Strategy for Osteochondral Regeneration Based on a 3D Printable Biomimetic Scaffold with Kartogenin Biochemical Stimuli Gradient

Wei

Liu

Kang

et al. 2023

Adv Healthcare Materials

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Osteochondral defect (OCD) regeneration remains challenging because of the hierarchy of the native tissue including both the articular cartilage and the subchondral bone. Constructing an osteochondral scaffold with biomimetic composition, structure, and biological functionality is the key to achieve its high-quality repair. In the present study, an injectable and 3D printable bilayered osteochondral hydrogel based on compositional gradient of methacrylated sodium alginate, gelatin methacryloyl, and 𝜷-tricalcium phosphate (𝜷-TCP), as well as the biochemical gradient of kartogenin (KGN) in the two well-integrated zones of chondral layer hydrogel (CLH) and osseous layer hydrogel (OLH) is developed. In vitro and subcutaneous in vivo evaluations reveal that apart from the chondrogenesis of the embedded bone mesenchymal stem cells induced by CLH with a high concentration of KGN, a low concentration of KGN with 𝜷-TCP in the OLH synergistically achieves superior osteogenic differentiation by endochondral ossification, instead of the intramembranous ossification using OLH with only 𝜷-TCP. The biomimetic construct leveraging KGN as the only biochemical inducer can facilitate cartilage and subchondral bone restoration in the in vivo osteochondral defect. This one-stone-two-birds strategy opens up a new facile approach for OCD regeneration by exploiting the biological functions of the bioactive drug molecule KGN.

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Section: Resultsmentioning

confidence: 99%

A One‐Stone‐Two‐Birds Strategy for Osteochondral Regeneration Based on a 3D Printable Biomimetic Scaffold with Kartogenin Biochemical Stimuli Gradient

Wei

Liu

Kang

et al. 2023

Adv Healthcare Materials

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“…Callus undergoes hypertrophy, calcification, apoptosis, osteogenic progenitor cell recruitment and osteogenic differentiation to achieve new bone production. 5 Based on this stage of bone regeneration, Ouyang et al 6 used digital light processing printing technology to load hydrogel microspheres with bone marrow MSCs. They then used chondrogenic induction medium to induce MSCs to differentiate and successfully constructed callus organoids.…”

Section: Organoidsmentioning

confidence: 99%

Organoid and organoid extracellular vesicles for osteoporotic fractures therapy: Current status and future perspectives

Liu

2023

Interdisciplinary Medicine

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Osteoporosis is a systemic and degenerative disease characterized by low bone mass and fragile microarchitecture, which predispose patients to fragility fractures, also known as osteoporotic fractures (OPF). OPF have become a major social problem that threaten the health of the elderly. Over the past decade, organoids and organoids extracellular vesicles (OEVs) play a significant role in OPF repair. Organoids have been widely used for fractures treatment. Moreover, EVs are promising nanocarriers due to their cell‐free system, stable drug loading capacity, nanometer size, and good biocompatibility. Importanly, compared with traditional EVs, OEVs have more quantity, better physiological effects, and better therapeutic effects. Therefore, the development of organoid and OEVs in the treatment of OPF is of great significance. Here, we summarize the current status and future perspectives of organoids and OEVs, which will provide innovative solutions to OPF repair.

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“…It also closely mimics the composition and behavior of stem progenitor cells in cartilage involved in osteogenesis. After in situ implantation, rapid bone repair was achieved within 4 weeks by advancing the regenerative process of endochondral osteogenesis, which indicates that in vitro construction of osteo-callus-like organs (osteo-callus organoids) according to developmental or regenerative processes is an effective strategy to promote rapid regeneration of bone tissue and the healing of bone defects [ 217 ]. Ji et al developed a “building block” controlled drug delivery system with macrophage modulating and injectable properties consisting of porous chitosan (CS) microspheres and hydroxypropyl chitosan (HPCH) temperature-sensitive hydrogels, in which dimethoxyglycine (DMOG) was loaded into temperature-sensitive HPCH hydrogels and KGN was grafted onto porous CS microspheres, thus forming the HPCH hydrogels/CS microspheres composite scaffold, which can effectively regulate the regenerative microenvironment at the defect site, recruit autologous stem cells, and provide abundant cell adhesion sites, thus achieving M2 polarization of local macrophages and promoting osteochondral regeneration [ 218 ].…”

Section: Novel Applications Of Microspheres For Bone Tissue Engineeringmentioning

confidence: 99%

The Role of Microsphere Structures in Bottom-Up Bone Tissue Engineering

Feng

Wang

et al. 2023

Pharmaceutics

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Bone defects have caused immense healthcare concerns and economic burdens throughout the world. Traditional autologous allogeneic bone grafts have many drawbacks, so the emergence of bone tissue engineering brings new hope. Bone tissue engineering is an interdisciplinary biomedical engineering method that involves scaffold materials, seed cells, and “growth factors”. However, the traditional construction approach is not flexible and is unable to adapt to the specific shape of the defect, causing the cells inside the bone to be unable to receive adequate nourishment. Therefore, a simple but effective solution using the “bottom-up” method is proposed. Microspheres are structures with diameters ranging from 1 to 1000 µm that can be used as supports for cell growth, either in the form of a scaffold or in the form of a drug delivery system. Herein, we address a variety of strategies for the production of microspheres, the classification of raw materials, and drug loading, as well as analyze new strategies for the use of microspheres in bone tissue engineering. We also consider new perspectives and possible directions for future development.

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High-efficient engineering of osteo-callus organoids for rapid bone regeneration within one month

Cited by 68 publications

References 47 publications

A One‐Stone‐Two‐Birds Strategy for Osteochondral Regeneration Based on a 3D Printable Biomimetic Scaffold with Kartogenin Biochemical Stimuli Gradient

A One‐Stone‐Two‐Birds Strategy for Osteochondral Regeneration Based on a 3D Printable Biomimetic Scaffold with Kartogenin Biochemical Stimuli Gradient

Organoid and organoid extracellular vesicles for osteoporotic fractures therapy: Current status and future perspectives

The Role of Microsphere Structures in Bottom-Up Bone Tissue Engineering

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