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Biomedical Materials · 2019 ·Vol. 14 ·期 6 ·065007 · IF 3.44

A comparative study on agarose acetate and PDLLA scaffold for rabbit femur defect regeneration

Ruifang Zhao,Zunkai Xu,Bing Li,Tao Chen,Naibin Mei,Chuang Wang,Zongbao Zhou,Lingling You,Chaoxi Wu,Xiaoying Wang,Shunqing Tang

The development of degradable polymer scaffolds is a key issue in bone regeneration. Poly(D, L-lactide) (PDLLA) and its derivatives have usually been applied to the construction of degradable scaffolds, but these scaffolds had problems with acidic degradation products and quick loss of mechanic strength during the later degradation, which usually led to scaffold collapse and cavity formation because of the slower rate of bone regeneration. In the present paper, a polysaccharide derivative, agarose acetate (AGA), was synthesized and a novel porous AGA scaffold was successfully developed through a salt-leaching process. The AGA scaffold had over 90% porosity without swelling in water, and compared to collapse and acidic products of PDLLA scaffold during degradation, the AGA scaffold maintained a stable morphology and a nearly neutral pH value over 18 months' degradation in PBS. A bone mesenchymal stem cells (BMSCs) adhesion and proliferation experiment showed that more cells adhered to the AGA scaffold than to the PDLLA scaffold. A subcutaneous implant test showed that the AGA scaffold slowly degraded and did not cause an inflammatory response surrounding the implantation lesion site. AGA scaffold was implanted into femur defects in New Zealand white rabbits to test its in vivo performance. Results indicated that the AGA scaffold accelerated the process of bone regeneration compared to the PDLLA group and, with time, new bone was formed from the margin toward the center of the scaffolds, and the scaffold left in place retained its porous structure without collapsing. Meanwhile, the AGA scaffold showed a low degradation rate and kept its shape during the in vivo degradation compared to the PDLLA scaffold. This performance could have the benefit of integrated regenerative bone being formed instead of cavities due to the quickly degraded scaffold disappearing. These results demonstrate that the AGA scaffold has significant potential in bone regeneration applications.

CAS / MDL: 9012-36-6
研究领域: 组织工程 · 生物医用材料 · 骨科
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Wood-inspired highly anisotropic scaffold activated with in situ mineralized collagen for advanced bone regeneration

Lili Wang,Xian Chen,Ruixue Guo,Shenghong Wang,Hongtao Zhang,Fengjuan Chen,Jianxi Xiao

Addressing bone defects, limited by inherent regenerative capacities, has catalyzed the development of biomimetic scaffolds. Despite the extensive exploration of collagen-hydroxyapatite scaffolds, they frequently fail to accurately replicate the intricate nanostructure of natural bone. We introduce the wood-collagen- hydroxyapatite (WCH) scaffold, a novel biomimetic structure inspired by the analogous architectures of wood and bone, aimed at substantially improving bone regeneration. Comprising a wood-based matrix, collagen interface, and hydroxyapatite mineralization, the WCH scaffold embodies the critical components of bone tissue. The scaffold’s wood-derived framework imparts an anisotropic structure and notable mechanical strength, closely mimicking natural bone’s nanoarchitecture. Significantly, the scaffold’s longitudinal (L) orientation outperforms its radial counterpart in biocompatibility and bioactivity, reflecting bone’s directional properties and promoting superior cell proliferation, adhesion, and osteogenic differentiation. Validated in a rabbit femur defect model, the L directional WCH scaffold significantly accelerated new bone formation, tissue ingrowth, and bone tissue maturation. This innovative wood-inspired scaffold, characterized by its highly anisotropic structure and enhanced with in-situ mineralized collagen, holds significant promise for advancing bone regeneration techniques.

CAS / MDL: 7758-19-2
研究领域: 生物材料 · 组织工程 · 生物医学工程 · 骨科
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CERAMICS INTERNATIONAL · 2024 · IF 5.1

Self-setting calcium phosphate cement scaffolds with pre-forming and in-situ forming interconnected macropores: Comparative study in vitro and in vivo

Guowen Qian,Peirong Fan,Jiandong Ye

Creating interconnected macropores in calcium phosphate cement (CPC) is an effective strategy to promote its degradation and osteogenesis. However, little attention has been given to the osteogenic effect of the CPC scaffolds with pre-forming and in-situ forming interconnected macropores. Herein, two types of CPC scaffolds were prepared by infiltrating CPC pastes into 3D-printed polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) networks. Meanwhile, the sacrificial PCL network within CPC was dissolved to obtain the CPC scaffold with approximately 300 μm macropores, whereas the PLGA network was retained within the CPC to obtain the PLGA/CPC scaffold. The results indicated that the PLGA/CPC scaffold showed higher degradation rate and compressive strength compared to the CPC scaffold with pre-forming interconnected macropores. However, the proliferation rate and alkaline phosphatase activity of mouse bone mesenchymal stem cells cultured with the CPC scaffold were superior to those cultured with the PLGA/CPC scaffold. In addition, greater formation of new bone and material degradation in the CPC scaffold compared to the PLGA/CPC scaffold after implanted in the rabbit femoral defects.

研究领域: 生物材料 · 组织工程 · 生物医学工程 · 骨科
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Applied Materials Today · 2019 · IF 8.013

Enhanced bacteriostatic activity, osteogenesis and osseointegration of silicon nitride/polyetherketoneketone composites with femtosecond laser induced micro/nano structural surface

Han Wu,Tao Liu,Zhiyan Xu,Jun Qian,Xuening Shen,Yuan Li,Yongkang Pan,Deqiang Wang,Kai Zheng,Aldo R. Boccaccini,Jie Wei

Poor cell adhesion and osteogenic activity impede the bone regeneration and osseointegration effects of polyetherketoneketone (PEKK) implants. Surface modification and incorporation of bioactive fillers are effective strategies to promote the cellular responses of PEKK implants and their integration with bone tissues. In this study, silicon nitride (SN) microparticles were blended with PEKK to develop bioactive composite implants (SPC). Femtosecond laser was then used to modify SPC surfaces inducing favorable micro/nano structural surface (FSPC). After the laser ablation, irregularly shaped SN microparticles were converted to “petal-like” clusters composed of “pin-like” SN nanoparticles, while the entire surface was covered by SN particles due to the removal of PEKK. The roughness, hydrophilicity, content of surface chemical groups ( e.g. , -NH 2 ), and protein adsorption capability of FSPC were significantly enhanced compared to SPC and PEKK. Also, the release of biologically active Si ions was increased after the femtosecond laser treatment, inducing a positive microenvironment favorable for cellular activities. Moreover, FSPC exhibited a greater bacteriostatic activity against Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) than SPC. The presence of micro/nano structure also remarkably promoted adhesion, proliferation, and osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs). In vivo evaluation of the composites in a rabbit femur defect model verified that FSPC could enhance osteogenesis and osseointegration to a greater extent than SPC, evidenced with greater bone-implant contacts and push-out force. These results indicate that the femtosecond laser induced micro/nano structural surface on SN/PEKK implants can significantly promote osseointegration and bone repair. The femtosecond laser exhibits great potential in surface modifying bioceramic/polymer composites. The fabricated FSPC have shown great potential as bone implants in orthopedic applications considering their excellent biocompatibility, bacteriostatic property, osteogenic activity, and osseointegration.

CAS / MDL: 7440-31-5
研究领域: 生物材料 · 生物医学工程 · 骨科 · 表面科学 · 组织工程
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ACS Applied Materials & Interfaces · 2019 · IF 8.456

Vancomycin- and Strontium-Loaded Microspheres with Multifunctional Activities against Bacteria, in Angiogenesis, and in Osteogenesis for Enhancing Infected Bone Regeneration

Pengfei Wei,Wei Jing,Zuoying Yuan,Yiqian Huang,Binbin Guan,Wenxin Zhang,Xu Zhang,Jianping Mao,Qing Cai,Dafu Chen,Xiaoping Yang

Biomaterials that have capacities to simultaneously induce bone regeneration and kill bacteria are in demand because bone defects face risks of severe infection in clinical therapy. To meet the demand, multifunctional biodegradable microspheres are fabricated, which contain vancomycin to provide antibacterial activity and strontium-doped apatite to provide osteocompatibility. Moreover, the strontium component shows activity in promoting angiogenesis, which further favors osteogenesis. For producing the microspheres, vancomycin is loaded into mesoporous silica and embedded in polylactide-based microspheres via the double emulsion technique and the strontium-doped apatite is deposited onto the microspheres via biomineralization in strontium-containing simulated body fluid. Sustained release behaviors of both vancomycin and Sr2+ ions are achieved. The microspheres exhibit strong antibacterial effect against Staphylococcus aureus, while demonstrating excellent cell/tissue compatibility. Studies of differentiation confirm that the introduction of strontium element strengthens the angiogenic and osteogenic expressions of mesenchymal stromal cells. Subcutaneous injection of the microspheres into rabbit’s back confirms their effectiveness in inducing neovascularization and ectopic osteogenesis. Finally, an infected rabbit femoral condyle defect model is created with S. aureus infection and the multifunctional microspheres are injected, which display significant antibacterial activity in vivo and achieve efficient new bone formation in comparison with biomineralized microspheres without vancomycin loading. The vancomycin- and strontium-loaded microspheres, being biomineralized, injectable, and biodegradable, are attractive because of their flexibility in integrating multiple functions into one design, whose potentials in treating infected bone defects are highly expected.

研究领域: 生物材料 · 组织工程 · 生物医学工程 · 药剂学 · 骨科 · 传染病学
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Bioactive Materials · 2024 · IF 18

Imidazole functionalized photo-crosslinked aliphatic polycarbonate drug-eluting coatings on zinc alloys for osteogenesis, angiogenesis, and bacteriostasis in bone regeneration

Wei Zhang,Miao Dai,Ye Zhu,Siyuan Li,Ying Sun,Xiaoya Liu,Xiaojie Li

Zinc (Zn) alloys have demonstrated significant potential in healing critical-sized bone defects. However, the clinical application of Zn alloys implants is still hindered by challenges including excessive release of zinc ions (Zn 2+ ), particularly in the early stage of implantation, and absence of bio-functions related to complex bone repair processes. Herein, a biodegradable aliphatic polycarbonate drug-eluting coating was fabricated on zinc-lithium (Zn–Li) alloys to inhibit Zn 2+ release and enhance the osteogenesis, angiogenesis, and bacteriostasis of Zn alloys. Specifically, the photo-curable aliphatic polycarbonates were co-assembled with simvastatin and deposited onto Zn alloys to produce a drug-loaded coating, which was crosslinked by subsequent UV light irradiation. During the 60 days long-term immersion test, the coating showed distinguished stable drug release and Zn 2+ release inhibition properties. Benefiting from the regulated release of Zn 2+ and simvastatin, the coating facilitated the adhesion, proliferation, and differentiation of MC3T3-E1 cells, as well as the migration and tube formation of EA.hy926 cells. Astonishingly, the coating also showed remarkable antibacterial properties against both S. aureus and E. coli . The in vivo rabbit critical-size femur bone defects model demonstrated that the drug-eluting coating could efficiently promote new bone formation and the expression of platelet endothelial cell adhesion molecule-1 (CD31) and osteocalcin (OCN). The enhancement of osteogenesis, angiogenesis, and bacteriostasis is achieved by precisely controlling of the released Zn 2+ at an appropriate level, as well as the stable release profile of simvastatin. This tailored aliphatic polycarbonate drug-eluting coating provides significant potential for clinical applications of Zn alloys implants.

研究领域: 材料科学 · 生物材料 · 生物医学工程 · 骨科 · 药理学
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

A multifunctional highly adhesive hydrogel mimicking snail mucus for hemostatic coating

Jingjing Yuan,Menghan He,Jueying Yang,Kang Li,Kexiang Fan,Hang Luo,Bo Li,Yu Chen

Femur fracture becomes increasingly common due to global population aging. Intramedullary nailing, a widely used treatment for fractures, tends to damage the blood vessels in the bone marrow cavity, which causes substantial hidden bleedings. The application of hydrogels to intramedullary nail hemostasis is limited by the challenges in balancing the adhesion, mechanical strength, and toughness. Inspired by the multi-network structure of snail mucus, which offers strong adhesion in harsh environments via adaptive wet-state contact followed by tight fitting upon dehydration, we developed a dual-network carboxymethyl chitosan (CMCS)-gluconic acid δ-lactone (GDL)-Ca 2+ /polyacrylamide (PAM) (CGC/P) hydrogel. The integration of GDL with CMCS introduces hydroxyl groups to enhance the adhesion of hydrogel and regulated system pH to facilitate the formation of the dynamic CMCS-GDL-Ca 2+ physical crosslinking network. The chemically crosslinked PAM network further improves the strength and toughness of the hydrogel. As the adhesion strength of the hydrogel can be increased by up to 50.14 times upon dehydration, a stretch-winding and dehydration method is developed to coat intramedullary nails with controllable thickness, effective hemostatic properties, excellent mechanical and adhesion characteristics. In rabbit femoral intramedullary nailing surgery, this system achieves rapid hemostasis and greatly promotes osteogenesis. Our study simultaneously improves the performance regulation contradiction of hydrogel coating, providing a crucial support to promote the application of hemostatic coatings to implantations.

CAS / MDL: 79-06-1 90-80-2
研究领域: 生物医学工程 · 材料科学 · 组织工程 · 骨科 · 生物材料
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