Bioinspired Mineralization Using Chondrocyte Membrane Nanofragments

Hara, Emilio Satoshi; Okada, Masahiro; Nagaoka, Noriyuki; Hattori, Takako; Kuboki, Takuo; Nakano, Takayoshi; Matsumoto, Takuya

doi:10.1021/acsbiomaterials.7b00962

Cited by 26 publications

(76 citation statements)

References 33 publications

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“…A possible mechanism could be associated with early phosphatase activity (data not shown), which is known to be fundamental for bone mineralization . Collectively, these data is in accordance with a previous article showing that nanofragments from cell membrane can also be nucleation site for mineral formation . Therefore, nanofragmentation of cell and MV structures can be an important tool for enhancing mineralization toward in vitro bone tissue synthesis.…”

Section: Discussionsupporting

confidence: 88%

“…25 Additionally, in our previous article, we have demonstrated that amorphous calcium phosphate minerals can be preserved even after preparation of thin TEM film samples, as confirmed by elemental mapping and electron diffraction. 3 Therefore, the results of this study indicate that an amorphous mineral phase is initially formed inside the MVs, which then crystallize into hydroxyapatite.…”

Section: Discussionmentioning

confidence: 68%

“…For instance, Irving reported important findings in the identification of phospholipids, which are the major components of plasma membranes, in the stages preceding mineralization of bones (intramembranous and endochondral ossifications) and tooth . These phospholipids were further identified to be cell‐secreted MVs, or cell membrane nanofragments . In the case of cell membrane nanofragments, which do not show a spherical shape, phosphate groups in the phospholipids constituting the membranes can directly interact with calcium ions present in the extracellular environment, promoting initial mineralization.…”

Section: Discussionmentioning

confidence: 99%

“…16 These phospholipids were further identified to be cell-secreted MVs 5,6,17 , or cell membrane nanofragments. 3 In the case of cell membrane nanofragments, which do not show a spherical shape, phosphate groups in the phospholipids constituting the membranes can directly interact with calcium ions present in the extracellular environment, promoting initial mineralization. On the other hand, mineralization in MVs is known to occur at the inner side of the MV membrane.…”

Section: Discussionmentioning

confidence: 99%

“…26 Collectively, these data is in accordance with a previous article showing that nanofragments from cell membrane can also be nucleation site for mineral formation. 3 Therefore, nanofragmentation of cell and MV structures can be an important tool for enhancing mineralization toward in vitro bone tissue synthesis. Nonetheless, isolation and collection of MVs in large amounts, which currently involves in vitro expansion of an enormous quantity of cells, is still a major problem hindering further development of bone tissue engineering techniques.…”

Section: Discussionmentioning

confidence: 99%

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Biomimetic mineralization using matrix vesicle nanofragments

Kunitomi

Hara

Okada

et al. 2019

J Biomedical Materials Res

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In vitro synthesis of bone tissue has been paid attention in recent years; however, current methods to fabricate bone tissue are still ineffective due to some remaining gaps in the understanding of real in vivo bone formation process, and application of the knowledge in bone synthesis. Therefore, the objectives of this study were first, to perform a systematic and ultrastructural investigation of the initial mineral formation during intramembranous ossification of mouse calvaria from a material scientists' viewpoint, and to develop novel mineralization methods based on the in vivo findings. First, the very initial mineral deposition was found to occur at embryonic day E14.0 in mouse calvaria. Analysis of the initial bone formation process showed that it involved the following distinct steps: collagen secretion, matrix vesicle (MV) release, MV mineralization, MV rupture, and collagen fiber mineralization. Next, we performed in vitro mineralization experiments using MVs and hydrogel scaffolds. Intact MVs embedded in collagen gel did not mineralize, whereas, interestingly, MV nanofragments obtained by ultrasonication could promote rapid mineralization. These results indicate that mechanically ruptured MV membrane can be a promising material for in vitro bone tissue synthesis. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1021–1030, 2019.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Biomimetic mineralization using matrix vesicle nanofragments

Kunitomi

Hara

Okada

et al. 2019

J Biomedical Materials Res

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Distinct Morphologies of Bone Apatite Clusters in Endochondral and Intramembranous Ossification

et al. 2022

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acid) [2] have been widely applied for this purpose. Nevertheless, these materials present limitations related to mimicking the biological and/or biomechanical properties of natural bone apatite. For instance, although hydroxyapatite-based bone mimetics present chemical similarities with natural bone, they show poor resorbability and remain in the transplanted area even after 10 years. [1] Alternative therapeutics using growth factors (e.g., bone morphogenetic protein 2 and basic fibroblast growth factor), [3] or cells, such as osteoblasts or mesenchymal stem/progenitor cells (MSCs), have also been introduced. [4] These methods, however, are costly and time-consuming, because cell therapies usually involve the transplantation of mature osteoblasts, and osteoblastic differentiation requires ≈2-3 weeks. [5] Recent multidisciplinary approaches merging the knowledge in developmental biology with methods/techniques in tissue engineering have enabled the development of unprecedented technologies for cartilage and bone tissue engineering. [6] In this context, previous approaches for promoting bone regeneration were suboptimal as they were essentially based only on the concept of osteoblast-driven intramembranous ossification (IO).Bone is formed through two distinct processes: IO and endochondral ossification (EO). [7] Intramembranous ossification begins inside the osteoblast-secreted extracellular vesicles, i.e., matrix vesicles (MVs), and forms the flat bones (e.g., skull) and the cortical bone. [7][8][9] Matrix vesicles refer to small (20-200 nm) spherical bodies transported via lysosome and secreted by exocytosis from the cells, mainly osteoblasts. [10,11] On the other hand, in EO, bone replaces a cartilage intermediate. [12] Recently, EO was shown to initiate from chondrocyte-derived plasma membrane nanofragments (PMNFs), in the absence of osteoblasts and MVs. [8,13] Previous studies have shown that the membrane and enzymes constituting MVs are different from the parent cell membrane. [14,15] On the other hand, PMNFs are direct fragments of the parent cell membrane. Thus, MVs and PMNFs could be regarded to have different composition in phospholipids and enzymes, [14,16] and could be leading to the formation of apatite clusters with different structures. However, little is known about the exact morphology of bone apatite clusters formed from MVs (IO) and PMNFs (EO).

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Spherulitic Crystal Growth Drives Mineral Deposition Patterns in Collagen‐Based Materials

Macías‐Sánchez

Tarakina

Ivanov

et al. 2022

Adv Funct Materials

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The formation of the hard tissues that provide support and mobility to organisms is achieved through the interplay of inorganic crystals and an organic framework composed of collagen and a small percentage of non‐collagenous proteins. Despite their clinical relevance, the mechanisms governing mineralization of the extracellular matrix are still poorly understood. By using 3D electron tomography and high‐resolution electron microscopy imaging and spectroscopy, it has been demonstrated that mineralization proceeds through a spherulitic‐like crystal growth process. First, aggregates of disordered crystals form in the interfibrillar spaces, which lead to the mineralization of adjacent fibrils. Mineral propagates steadily through the inter‐ and intrafibrillar spaces of the collagen structure forming layered spherulites that grow to confluence. The structure of the collagen fibrils serves as a protein scaffold to guide the formation of a myriad of platelet‐shaped crystallites that make up each of these spherulites. At their periphery, nanosized unmineralized areas remain, leading to the formation of the characteristic lacy pattern observed in the transversal cross‐section of mature calcified tissues. This study provides fundamental insights into the bone formation process and represents a potential strategy for complex materials design.

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Bioinspired Mineralization Using Chondrocyte Membrane Nanofragments

Cited by 26 publications

References 33 publications

Biomimetic mineralization using matrix vesicle nanofragments

Biomimetic mineralization using matrix vesicle nanofragments

Distinct Morphologies of Bone Apatite Clusters in Endochondral and Intramembranous Ossification

Spherulitic Crystal Growth Drives Mineral Deposition Patterns in Collagen‐Based Materials

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