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Bioactive Materials · 2024 · IF 18

Injectable double-crosslinked bone cement with enhanced bone adhesion and improved osteoporotic pathophysiological microenvironment for osteoregeneration in osteoporosis

Lingfei Zhao,Chenyu Liu,Xing Chen,Zirui He,Shuiquan Zhang,Anan Zhang,Shuaimin Tang,Zihan Wu,Changsheng Liu,Yuan Yuan

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.

研究领域: 生物材料学 · 骨科医学 · 再生医学
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Biomaterials Research · 2022 ·Vol. 26 ·期 1 ·1-22 · IF 15.863

Periosteum-inspired in situ CaP generated nanocomposite hydrogels with strong bone adhesion and superior stretchability for accelerated distraction osteogenesis

Lou Tengfei,Chen Kai,Luo Qiyu,Liu Changsheng,Yuan Yuan,Fan Cunyi

Background Distraction osteogenesis (DO) is an efficacious but lengthy procedure to reconstruct segmental bone defects under the principle of tension-stress, during which the periosteum-mediated mechanical stimulation plays a pivotal role. Inspired by the dynamic process of DO and the mechanical stimulation of periosteum, a new design of bionic periosteum was developed to simulate the mechanical transduction of natural periosteum for the application in DO procedure.Methods In this study, an injectable organic-inorganic hybrid hydrogel was developed based on a novel combination of the PEGylated poly (glycerol sebacate) (PEGS) polymer network and in situ formed CaP nanoparticles (ICPNs). Rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs) were cultured and tested in vitro to evaluate biocompatibility, cell adhesion, proliferation, and pro-osteogenic and pro-angiogenic activity. In vivo experiments were conducted in the rat tibial model of distraction osteogenesis.Results The developed nanocomposite hydrogels exhibited excellent injectability, robust bone adhesion, superior stretchability, and enhanced osteogenic activity. The results of in vitro and in vivo studies showed that PEGS/ICPN hydrogels could promote new bone formation and mineralization during the dynamic distraction process through the synergistic effects of angiogenesis and osteogenesis.Conclusion sThis periosteum-inspired nanocomposite hydrogel represents a mechanobiology approach for effectively restoring large bone defects through the dynamic DO process.

CAS / MDL: 7722-76-1 111-20-6
研究领域: 生物医学工程 · 组织工程 · 再生医学 · 材料科学 · 骨科
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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-25 · IF 10.6

Injectable ultrasound-powered bone-adhesive nanocomposite hydrogel for electrically accelerated irregular bone defect healing

Zhou Shiqi,Xiao Cairong,Fan Lei,Yang Jinghong,Ge Ruihan,Cai Min,Yuan Kaiting,Li Changhao,Crawford Ross William,Xiao Yin,Yu Peng,Deng Chunlin,Ning Chengyun,Zhou Lei,Wang Yan

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.

CAS / MDL: 10138-52-0 81-88-9
研究领域: 骨科 · 生物材料 · 组织工程 · 纳米技术 · 生物医学工程
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