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用于骨组织再生的铜掺杂磷酸钙超微粒

Cu-doped calcium phosphate supraparticles for bone tissue regeneration.

作者信息

Höppel Anika, Bahr Olivia, Ebert Regina, Wittmer Annette, Seidenstuecker Michael, Carolina Lanzino M, Gbureck Uwe, Dembski Sofia

机构信息

Department Tissue Engineering and Regenerative Medicine (TERM), University Hospital Würzburg 97070 Würzburg Germany

Department of Musculoskeletal Tissue Regeneration, University of Würzburg 97074 Würzburg Germany.

出版信息

RSC Adv. 2024 Oct 17;14(45):32839-32851. doi: 10.1039/d4ra04769a.

Abstract

Calcium phosphate (CaP) minerals have shown great promise as bone replacement materials due to their similarity to the mineral phase of natural bone. In addition to biocompatibility and osseointegration, the prevention of infection is crucial, especially due to the high concern of antibiotic resistance. In this context, a controlled drug release as well as biodegradation are important features which depend on the porosity of CaP. An increase in porosity can be achieved by using nanoparticles (NPs), which can be processed to supraparticles, combining the properties of nano- and micromaterials. In this study, Cu-doped CaP supraparticles were prepared to improve the bone substitute properties while providing antibacterial effects. In this context, a modified sol-gel process was used for the synthesis of CaP NPs, where a Ca/P molar ratio of 1.10 resulted in the formation of crystalline β-tricalcium phosphate (β-TCP) after calcination at 1000 °C. In the next step, CaP NPs with Cu (0.5-15.0 wt%) were processed into supraparticles by a spray drying method. Cu release experiments of the different Cu-doped CaP supraparticles demonstrated a long-term sustained release over 14 days. The antibacterial properties of the supraparticles were determined against Gram-positive ( and ) and Gram-negative () bacteria, where complete antibacterial inhibition was achieved using a Cu concentration of 5.0 wt%. In addition, cell viability assays of the different CaP supraparticles with human telomerase-immortalized mesenchymal stromal cells (hMSC-TERT) exhibited high biocompatibility with particle concentrations of 0.01 mg mL over 72 hours.

摘要

磷酸钙(CaP)矿物因其与天然骨矿物相的相似性,作为骨替代材料展现出巨大潜力。除了生物相容性和骨整合性外,预防感染至关重要,尤其是鉴于对抗生素耐药性的高度关注。在这种情况下,可控的药物释放以及生物降解是取决于CaP孔隙率的重要特性。通过使用纳米颗粒(NPs)可以实现孔隙率的增加,这些纳米颗粒可以加工成超颗粒,兼具纳米材料和微米材料的特性。在本研究中,制备了铜掺杂的CaP超颗粒,以改善骨替代材料的性能并提供抗菌效果。在此背景下,采用改良的溶胶 - 凝胶法合成CaP NPs,其中Ca/P摩尔比为1.10,在1000°C煅烧后形成结晶β - 磷酸三钙(β - TCP)。下一步,通过喷雾干燥法将含铜(0.5 - 15.0 wt%)的CaP NPs加工成超颗粒。不同铜掺杂CaP超颗粒的铜释放实验表明,在14天内呈现长期持续释放。测定了超颗粒对革兰氏阳性(和)菌以及革兰氏阴性()菌的抗菌性能,使用5.0 wt%的铜浓度可实现完全抗菌抑制。此外,不同CaP超颗粒与人端粒酶永生化间充质基质细胞(hMSC - TERT)的细胞活力测定表明,在72小时内,颗粒浓度为0.01 mg/mL时具有高生物相容性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/269d/11483895/a0687a8a72ba/d4ra04769a-f1.jpg

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