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The osteoporotic bone defect caused by excessive activity of osteoclasts has posed a challenge for public healthcare. However, most existing bioinert bone cement fails to effectively regulate the pathological bone microenvironment and reconstruct bone homeostasis in the presence of osteoclast overactivity and osteoblast suppression. Herein, inspired by natural bone tissue, an in-situ modulation system for osteoporotic bone regeneration is developed by fabricating an injectable double-crosslinked PEGylated poly(glycerol sebacate) (PEGS)/calcium phosphate cement (CPC) loaded with sodium alendronate (ALN) (PEGS/CPC@ALN) adhesive bone cement. By incorporating ALN, the organic-inorganic interconnection within PEGS/CPC@ALN results in a 100 % increase in compression modulus and energy dissipation efficiency. Additionally, PEGS/CPC@ALN effectively adheres to the bone by bonding with amine and calcium ions present on the bone surface. Moreover, this in-situ regulation system comprehensively mitigates excessive bone resorption through the buffering effect of CPC to improve the acidic microenvironment of osteoporotic bone and the release of ALN to inhibit hyperactive osteoclasts, and facilitates stem cell proliferation and differentiation into osteoblasts through calcium ion release. Overall, the PEGS/CPC@ALN effectively regulates the pathological microenvironment of osteoporosis while promoting bone regeneration through synergistic effects of drugs and materials, thereby improving bone homeostasis and enabling minimally invasive treatment for osteoporotic defects.

A smart hydrogel dressing based on a physicochemically cross-linked network, integrating multi-functions of high plasticity, good skin adhesion and peelability, can automatically adjust the release of Ga3+ according to temperature and pH variations in the different wound microenvironments, which is capable of providing rapid, high-quality healing of infected wounds. [Display omitted] • One-step in situ polymerization for preparing hydrogel dressings with good conformability and peelability. • Ga3+ plays a dual role in improving the stability and antimicrobial effect of the dressing. • Hydrogel dressing can regulate Ga3+ release according to temperature and pH variation. • Wound healing tests show excellent wound healing rate and collagen deposition. The treatment of infected wounds remains challenging due to the lack of an ideal wound therapy material. Herein, We present a multifunctional hydrogel dressing material containing gallium ion (Ga3+) based on a physicochemical dual network via in situ free radical polymerization. The presence of Ga3+ not only improves the elasticity and thermal stability of the hydrogel dressing through chelation but also enables smart response release. Fabricated hydrogel dressing possesses large-area plasticity, adequate elasticity, skin adhesion, and peelability. Furthermore, the dressing is responsive to temperature and pH, which can intelligently release Ga3+ according to pH and temperature variations in different healing stages of the wound microenvironment. In vivo infected wound experiments validated the significant wound healing efficiency (healing ratio is 95.75 % in 7 days, 14 % higher than the control group). These results show the promising potential of the developed multifunctional materials for accelerating the healing of infected wounds. [ABSTRACT FROM AUTHOR]

BACKGROUND: Construction of tissue engineering vascular structures is a key to the regeneration of complex tissues and organs. The use of three-dimensional printing technology to construct vascular structures has become a hotspot. OBJECTIVE: A highly connected and perfusable vascular network was rapidly deposited by a three-dimensional bioprinter with a coaxial nozzle using alginate/silk fibroin bioink. METHODS: A mixed solution containing 5% sodium alginate and 5% silk fibroin as the bio-ink, and a mixed solution containing 5% calcium chloride and 13% F127 as the crosslinker, alginate/silk fibroin gel was printed using a bio-printer and subjected to optical coherence tomography and scanning electron microscopy. The solution containing 5% sodium alginate and 5% silk fibroin mixed with the suspension of human liver cancer cells (C3A) as the bio-ink, and a mixed solution containing 5% calcium chloride and 13% F127 as the crosslinker, the cell-containing sodium alginate/silk fibroin gel was printed on a bio-printer. Then, the printed scaffold was placed in the medium for 24 hours, and then stained by Calcein-AM and observed under a fluorescence microscope. RESULTS AND CONCLUSION: (1) Optical coherence tomography: a multi-layer composite hollow tube network formed the structure of the scaffold. The gel filament had a complete hollow structure, and the channels were interconnected. The structure was similar to the hollow passage of the blood vessel, which was beneficial to the transportation of nutrients and metabolic waste. (2) Scanning electron microscope: the hollow pipe structure with the diameter of about 400 μm arranged in parallel, and the pipe boundaries were clear. The microporous structure caused by the removal of F127 was formed between the boundaries. (3) Fluorescence microscope: the cells were evenly dispersed in the material on both sides of the channel, and the cells grew well in the scaffold with the survival rate of above 95%. (4) These results suggest that three-dimensional bioprinting technology based on coaxial nozzles and sodium alginate/silk fibroin bio-ink can be used to construct vascularized functional tissues in the future. [ABSTRACT FROM AUTHOR]