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用于骨组织工程支架的自愈合、生物活性和双交联多糖基复合水凝胶的3D打印

3D Printing of a Self-Healing, Bioactive, and Dual-Cross-Linked Polysaccharide-Based Composite Hydrogel as a Scaffold for Bone Tissue Engineering.

作者信息

Nasiripour Saba, Pishbin Fatemehsadat, Seyyed Ebrahimi S A

机构信息

School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, North Kargar Street, Tehran 11155-4563, Iran.

Advanced Magnetic Materials Research Center, School of Metallurgy and Materials Engineering, College of Engineering, University of Tehran, North Kargar Street, Tehran 11155-4563, Iran.

出版信息

ACS Appl Bio Mater. 2025 Jan 20;8(1):582-599. doi: 10.1021/acsabm.4c01476. Epub 2025 Jan 7.

DOI:10.1021/acsabm.4c01476
PMID:39764630
Abstract

Although 3D printing is becoming a dominant technique for scaffold preparation in bone tissue engineering (TE), developing hydrogel-based ink compositions with bioactive and self-healing properties remains a challenge. This research focuses on developing a bone scaffold based on a composite hydrogel, which maintains its self-healing properties after incorporating bioactive glass and is 3D-printable. The plain hydrogel ink was synthesized using natural polymers of 1 wt % N-carboxyethyl chitosan, 2 wt % hyaluronic acid aldehyde, 0.3 wt % adipic acid hydrazide, and alginate (ALG) (2, 5, and 10 wt %). Bioactive glass (BG) (0 and 5 w/v %) particles were incorporated into the plain matrix to obtain an osteogenic composite hydrogel. The material was characterized via rheology, field emission scanning electron microscopy/energy-dispersive X-ray spectroscopy (FESEM/EDS), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), swelling, degradation, bioactivity, and in vitro cellular assessments. Rheological evaluations confirmed that the specimen with 0 w/v % BG and 5 wt % ALG exhibited the highest ', ″, and viscosity values. All specimens exhibited self-healing, provided by two reversible dynamic bonds, namely, imine and acylhydrazone. Bioactivity evaluation by SBF immersion revealed the formation of HA particles on the composite hydrogels. MTT cytotoxicity assay on MG63 indicated that the composite sample containing 5 w/v % BG and 10 wt % ALG had the highest cell viability (95 ± 1.02%) by culture day 3. The developed approach presents a promising hydrogel ink formulation with a high potential for extrusion-based 3D printing of bone TE constructs.

摘要

尽管3D打印正成为骨组织工程(TE)中支架制备的主导技术,但开发具有生物活性和自愈性能的水凝胶基油墨组合物仍然是一项挑战。本研究专注于开发一种基于复合水凝胶的骨支架,该支架在加入生物活性玻璃后仍保持其自愈性能且可3D打印。普通水凝胶油墨使用1 wt%的N-羧乙基壳聚糖、2 wt%的透明质酸醛、0.3 wt%的己二酸酰肼和藻酸盐(ALG)(2、5和10 wt%)的天然聚合物合成。将生物活性玻璃(BG)(0和5 w/v%)颗粒加入到普通基质中以获得具有成骨作用的复合水凝胶。通过流变学、场发射扫描电子显微镜/能量色散X射线光谱(FESEM/EDS)、傅里叶变换红外(FTIR)光谱、X射线衍射(XRD)、溶胀、降解、生物活性和体外细胞评估对材料进行了表征。流变学评估证实,含0 w/v% BG和5 wt% ALG的试样表现出最高的'、''和粘度值。所有试样均表现出自愈性能,这由亚胺和腙两种可逆动态键提供。通过SBF浸泡进行的生物活性评估显示复合水凝胶上形成了HA颗粒。对MG63进行的MTT细胞毒性试验表明,含5 w/v% BG和10 wt% ALG的复合样品在培养第3天时具有最高的细胞活力(95±1.02%)。所开发的方法提出了一种有前景的水凝胶油墨配方,具有基于挤压的骨TE构建体3D打印的高潜力。

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