Carnosine Biofunctionalized Hydroxyapatite Induces Copper-Driven Osteogenesis and Angiogenesis, Strengthening Its Bone Regenerative Capacities.

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Biomaterials Science & Engineering Pub Date : 2025-08-31 DOI:10.1021/acsbiomaterials.5c00823

Irina Naletova, Francesco Attanasio, Teresa Sibillano, Barbara Tomasello, Valeria Lanza, Valeria Ciaffaglione, Rita Tosto, Antonio Mio, Warren Cairns, Cinzia Giannini, Enrico Rizzarelli

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Abstract

Hydroxyapatite (Hap) is a prominent biomaterial used as an effective implant material in bone tissue engineering, but its use presents some points of weakness in bone regeneration efficiency. Different biofunctionalization strategies have been utilized to increase the regenerative Hap capacities. Carnosine (Car) or β-alanyl-l-histidine dipeptide has received much attention due to its beneficial effects in osteoarticular diseases and bone tissue healing. Hap functionalized in noncovalent mode with Car at a nominal Ca:Car molar ratio (10:1, 2:1, and 1:1) was synthesized. The Hap-Car composites were characterized by using X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopies. The structural and morphological feature comparisons indicate a similarity between Hap-Car10:1 and Hap. The Hap-Car composites and Hap bind copper present at submicromolar concentration in the complete culture medium, determined by inductively coupled plasma-optical emission spectroscopy. Hap-Car composites enhance the biological properties of Hap in in vitro assays and promote the mineralization process and the expression of alkaline phosphatase, osteocalcin, vascular endothelial growth factor, brain derived neurotrophic factor, and bone morphogenetic protein-2 in hFOB1.19 cells. The protective and regenerative activities of the metal ion are also related to the intracellular chaperone copper chaperones for superoxide dismutase.

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肌肽生物功能化羟基磷灰石诱导铜驱动的骨生成和血管生成，增强其骨再生能力。

羟基磷灰石（Hydroxyapatite, Hap）是骨组织工程中常用的一种有效的生物材料，但其在骨再生效率方面存在不足。不同的生物功能化策略被用来提高Hap的再生能力。肌肽（Car）或β-丙烯酰-组氨酸二肽因其在骨关节疾病和骨组织愈合中的有益作用而受到广泛关注。以Ca:Car的名义摩尔比（10:1,2:1和1:1）合成了Hap与Car在非共价模式下的功能化。利用x射线衍射、扫描电镜和傅里叶变换红外光谱对Hap-Car复合材料进行了表征。结构和形态特征比较表明Hap- car10:1与Hap具有相似性。通过电感耦合等离子体发射光谱测定，Hap- car复合材料和Hap结合铜在完整培养基中以亚微摩尔浓度存在。在体外实验中，Hap- car复合材料增强了Hap的生物学特性，促进了hFOB1.19细胞的矿化过程和碱性磷酸酶、骨钙素、血管内皮生长因子、脑源性神经营养因子和骨形态发生蛋白-2的表达。金属离子对超氧化物歧化酶的保护和再生活性也与细胞内的伴侣铜伴侣有关。

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来源期刊

ACS Biomaterials Science & Engineering Materials Science-Biomaterials

CiteScore

10.30

自引率

3.40%

发文量

413

期刊介绍： ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics: Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture