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WIREs Nanomed Nanobiotechnol
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Advances of nanotechnology in osteochondral regeneration

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Abstract In the past few decades, nanotechnology has proven to be one of the most powerful engineering strategies. The nanotechnologies for osteochondral tissue engineering aim to restore the anatomical structures and physiological functions of cartilage, subchondral bone, and osteochondral interface. As subchondral bone and articular cartilage have different anatomical structures and the physiological functions, complete healing of osteochondral defects remains a great challenge. Considering the limitation of articular cartilage to self‐healing and the complexity of osteochondral tissue, osteochondral defects are in urgently need for new therapeutic strategies. This review article will concentrate on the most recent advancements of nanotechnologies, which facilitates chondrogenic and osteogenic differentiation for osteochondral regeneration. Moreover, this review will also discuss the current strategies and physiological challenges for the regeneration of osteochondral tissue. Specifically, we will summarize the latest developments of nanobased scaffolds for simultaneously regenerating subchondral bone and articular cartilage tissues. Additionally, perspectives of nanotechnology in osteochondral tissue engineering will be highlighted. This review article provides a comprehensive summary of the latest trends in cartilage and subchondral bone regeneration, paving the way for nanotechnologies in osteochondral tissue engineering. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement
Category of knee joint surface defects. Based on the Outerbridge classification system, the knee joint surface defects can be divided into Grade 0 (normal cartilage), Grade II (partial‐thickness defect), Grade III (full‐thickness defect), and Grade IV (osteochondral defect)
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The micro/nano hybrid structure significantly promotes the adhesion and differentiation of BMSCs. (a) SEM images, (b) hBMSC adhesion, (c) Immunostaining of cultured hBMSCs including Cx43 and cell cytoskeleton (green, Cx43; red, actin; blue, nuclei), (d) Immunostaining of Cx43. The HA scaffolds with micro/nano hybrid structures distinctly facilitate the osteogenic differentiation of hBMSCs and have the capability to promote the regeneration of bone. hBMSCs, human bone mesenchymal stem cells; S0, flat surface; S1, nanorod structured surface; S2, micropattern structured surface; S3, micropattern/nanorod hybrid structured surface (Zhao et al., )
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3D printing scaffolds with nanotopography for osteochondral regeneration. The BRT scaffolds were prepared by a 3D printing method, and then a hydrothermal process was employed to prepare the nanotopography on the surface of BRT scaffolds. The nanostructure can facilitate the differentiation of chondrocytes and BMSCs as well as promote the regeneration of osteochondral tissue (Deng et al., ). BMSCs, bone mesenchymal stem cells; BRT, bredigite
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Nanoparticle‐mediated labeling and targeting of chondrocytes and stem cells. Multiple nanoparticles, such as quantum dots, Fe3O4, SPIO, and gold, have been applied to chaperone cells or osteo/chondral tissue. In addition to MRI‐based tracking, nanoparticles may be used to track cells to osteochondral tissue through magnet‐ and CT‐based targeting. SPIO, superparamagnetic iron oxide
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Chondroitin sulfate nanoparticles and nanohydroxyapatite‐loaded hydrogel for osteochondral regeneration. (a) Gross morphology, (b) SEM of gradients in architecture, (c) SEM of the chondral architecture, (d) SEM of the osteochondral interface, (e) SEM of the subchondral architecture, (f) gross appearance of the defect at 8 weeks postsurgery, (g) coronary image of micro‐CT, (h) transverse image of micro‐CT. Dotted lines delineate the neotissue from native host tissue. D, defect site; NT, native tissue (Radhakrishnan et al., )
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Nanoparticle‐based strategies enhance therapeutic outcome. Nanoparticles can be divided into degradable and nondegradable nanoparticles. The degradable nanoparticles include chondroitin sulfate, collagen, poly (l‐lactide‐co‐glycolic) (PLGA), poly (l‐lactide) (PLA), polycaprolactone and HA, while the nondegradable nanoparticles consist of mesoporous silicon dioxide, gold nanoparticles, quantum dots, SPIOs, and lipids. Drugs, growth factors and genetic material‐loaded nanoparticles can promote the regeneration of osteochondral tissue at sites of pathology and fracture. HA, hydroxyapatite; SPIO, superparamagnetic iron oxide
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The structure of osteochondral tissue. The osteochondral tissue consists of the articular cartilage, subchondral bone, and osteochondral interface. The articular cartilage can be divided into the superficial zone, middle zone, deep zone, and calcified cartilage
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The development of treatment methods for osteochondral defects. The present strategies for the treatment of osteochondral defects can be divided into palliative treatment, reparative treatment, and restorative treatment. The typical treatment method, microfracture, was first used in 1997 and is suitable for Grade II/III osteochondral defects. With the development of scientific technologies, the future strategy for osteochondral defect treatment will be intelligent treatments, such as nanobots, 3D printing, artificial intelligence, and osteo‐mimicking and chondral‐mimicking materials. 3D, three‐dimensional; ACI, autologous chondrocytes implantation; Denovo NT/ET, DeNovo natural tissue/engineering tissue; MACI, matrix‐assisted chondrocyte implantation
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Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Implantable Materials and Surgical Technologies > Nanomaterials and Implants

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