Tolerant and Rapid Endochondral Bone Regeneration Using Framework‐Enhanced 3D Biomineralized Matrix Hydrogels

Abstract

Tissue‐engineered bone has emerged as a promising alternative for bone defect repair due to the advantages of regenerative bone healing and physiological functional reconstruction. However, there is very limited breakthrough in achieving favorable bone regeneration due to the harsh osteogenic microenvironment after bone injury, especially the avascular and hypoxic conditions. Inspired by the bone developmental mode of endochondral ossification, a novel strategy is proposed for tolerant and rapid endochondral bone regeneration using framework‐enhanced 3D biomineralized matrix hydrogels. First, it is meticulously designed 3D biomimetic hydrogels with both hypoxic and osteoinductive microenvironment, and then integrated 3D‐printed polycaprolactone framework to improve their mechanical strength and structural fidelity. The inherent hypoxic 3D matrix microenvironment effectively activates bone marrow mesenchymal stem cells self‐regulation for early‐stage chondrogenesis via TGFβ/Smad signaling pathway due to the obstacle of aerobic respiration. Meanwhile, the strong biomineralized microenvironment, created by a hybrid formulation of native‐constitute osteogenic inorganic salts, can synergistically regulate both bone mineralization and osteoclastic differentiation, and thus accelerate the late‐stage bone maturation. Furthermore, both in vivo ectopic osteogenesis and in situ skull defect repair successfully verified the high efficiency and mechanical maintenance of endochondral bone regeneration mode, which offers a promising treatment for craniofacial bone defect repair.

Screening of molecular markers associated with hornless traits in Qira black sheep

“…EYA2 gene has been shown to be closely associated with the biological processes of rhabdomyosarcoma tissue development, muscle cell and skeletal muscle cell differentiation(Ahbara et al 2019b), and its regulation of skeletal muscle cell differentiation regulates skeletal growth and development, while growth regulation of the horns has been closely linked to skeletal growth hypothesize that the horn is closely related to skeletal growth and development. We hypothesized that the skeletal growth as well as the development of the Qira black sheep is correlated with the angular trait.Ocstamp gene, NC_056066.1 (75223179..75230538, complement) located on chromosome 13 in sheep, is an osteoclastogenic gene for the gene osteoclast-stimulating transmembrane proteins(Nemeth et al 2011), which are associated with osteoclast differentiation(Peng et al 2022), and the rapid maturation of the bone is attributed to the e cient bone mineralization and reconstruction process realization, said bone reconstruction process involves the deposition of new bone and resorption of old bone(Bai et al 2024). Cell-cell fusion is another unique maturation process of osteoblasts accompanied by multinucleation, which is reportedly controlled by seven transmembrane proteins expressed by dendritic cells ( Dcstamp ) and osteoblast-stimulated transmembrane protein ( Ocstamp )(Omata et al 2023).…”