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The human cardiac organoid (hCO) is three-dimensional tissue model that is similar to an in vivo organ and has great potential on heart development biology, disease modeling, drug screening and regenerative medicine. However, the construction of hCO presents a unique challenge compared with other organoids such as the lung, small intestine, pancreas, liver. Since heart disease is the dominant cause of death and the treatment of such disease is one of the most unmet medical needs worldwide, developing technologies for the construction and application of hCO is a critical task for the scientific community. In this review, we discuss the current classification and construction methods of hCO. In addition, we describe its applications in drug screening, disease modeling, and regenerative medicine. Finally, we propose the limitations of the cardiac organoid and future research directions. A detailed understanding of hCO will provide ways to improve its construction and expand its applications. [ABSTRACT FROM AUTHOR]

Fabricating an organic–inorganic nanocomposite hydrogel platform with antibacterial, anti-inflammatory, and osteoinductive properties that mimic bone extracellular matrix composition is decisive for guiding bone development in orthopedic practice. Despite significant progress in developing hydrogels for tissue repair, little attention has been paid to replicating the natural bone ECM microenvironments and addressing the importance of anti-inflammatory agents during osteogenesis. Herein, we developed ciprofloxacin and dexamethasone loaded strontium (Sr) and/or iron (Fe) substituted hydroxyapatite (HAp) nanomaterials precipitated in collagen (Col) to construct a multifunctional bioactive nanocomposite hydrogel platform to prevent inflammation and bacterial adhesion, leading to augmenting bone development in the defect site. The fabricated nanocomposite hydrogels (Sr:HAp-Col, Fe:HAp-Col, and Sr/Fe:HAp-Col) were physicochemically characterized and demonstrated high loading and prolonged drug release, and excellent antibacterial activity against Gram-positive and Gram-negative bacteria. In in vitro experiments, the Sr/Fe:HAp-Col sample exhibited enhanced bioactivity against the preosteoblast MC3T3-E1 cell line, with high alkaline phosphatase and bone-like inorganic calcium deposition, as well as increased gene expression of osteogenesis-related differentiation markers, including OPN, OCN, and RUNX2. Furthermore, in vivo experiments revealed that the Sr/Fe:HAp-Col matrix degraded over time by controlling the release of ions into the body, without causing acute inflammation at the implanted site or in the blood serum, or in the internal organs, including the heart, lungs, liver, and kidney of the Sprague–Dawley rat model. The micro-CT scan and histological examination showed high bone mineral density and more mature bone formation at the nanocomposite hydrogel implanted site associated with the ColMA hydrogel in the femur defect of the rat model. The strategy of applying collagen hydrogel supplemented with HAp to bone regeneration is promising due to its ability to mimic the natural bone ECM. Overall, the developed bioactive nanocomposite hydrogel may have great potential not only in bone regeneration but also in repairing nonunion-infected defects of other tissues. [ABSTRACT FROM AUTHOR]

Wound healing is a multifaceted process that involves hemostasis, inflammation, proliferation, and remodeling stages. Diabetic wounds affect the transition of the organized phases and result in delayed healing due to impaired angiogenesis, chronic inflammation, bacterial infection, and insufficient growth factors. Multifunctional heterostructural nanoparticles enriched minimally invasive hydrogels for on-demand procedural distribution to aid wound healing at various stages has become a promising strategy. Herein, silk fibroin-hyaluronic acid based injectable hydrogels incorporated with mace-like Au–CuS heterostructural nanoparticles (gAu–CuS HSs) were used to cure diabetic wounds. SF–HA and the rough surface of gAu–CuS HSs confer a synergistic hemostatic phase with a nano-bridge effect and rapidly close the wounds. During the inflammation stage, gAu–CuS HSs perform in-space resonance energy transfer under 808 nm laser irradiation which in return produces reactive oxygen species for bacterial destruction. The unusual mace-like rough structure of nanoparticles causes macrophage transfer to the M2 phenotype, regulates cytokine expression (interleukin 6, transforming factor-β1, interferon γ, and interleukin-10), promotes angiogenesis, and promotes cell multiplication and fibroblast emigration to the wound area during the proliferation and remodeling phase. Overall, the gAu–CuS HSs reinforced injectable hydrogel programmatically accelerates wound healing and could represent a versatile strategy for advanced diabetic wound healing. [ABSTRACT FROM AUTHOR]

An injectable BMSC-encapsulated double network (DN) hydrogel was fabricated via silk fibroin (SF) and poly(ethylene glycol) (PEG), which could efficiently support the survival and proliferation of BMSCs in vitro as well as cartilage repair in vivo, and provides a new strategy for cartilage tissue engineering. [ABSTRACT FROM AUTHOR]