Poddar Deepak, Singh Ankita, Rao Pranshu, Mohanty Sujata, Jain Purnima
Department of Chemistry, Netaji Subhas University of Technology, Dwarka Sector 3, New Delhi, 110078, India.
Department of Chemical Engineering, Indian Institute of Technology Delhi, New Delhi, 110016, India.
Macromol Biosci. 2023 Dec;23(12):e2300243. doi: 10.1002/mabi.202300243. Epub 2023 Aug 24.
Three dimensional (3D) scaffolds have huge limitations due to their low porosity, mechanical strength, and lack of direct cell-bioactive drug contact. Whereas bisphosphonate drug has the ability to stimulate osteogenesis in osteoblasts and bone marrow mesenchymal stem cells (hMSC) which attracted its therapeutic use. However it is hard administration low bioavailability, and lack of site-specificity, limiting its usage. The proposed scaffold architecture allows cells to access the bioactive surface at their apex by interacting at the scaffold's interfacial layer. The interface of 3D polycaprolactone (PCL) scaffolds has been coated with alendronate-modified hydroxyapatite (MALD) enclosed in a chitosan matrix, to mimic the native environment and stupulate the through interaction of cells to bioactive layer. Where the mechanical strength will be provided by the skeleton of PCL. In the MALD composite's hydroxyapatite (HAP) component will govern alendronate (ALD) release behavior, and HAP presence will drive the increase in local calcium ion concentration increases hMSC proliferation and differentiation. In results, MALD show release of 86.28 ± 0.22. XPS and SEM investigation of the scaffold structure, shows inspiring particle deposition with chitosan over the interface. All scaffolds enhanced cell adhesion, proliferation, and osteocyte differentiation for over a week without in vitro cell toxicity with 3.03 ± 0.2 kPa mechanical strength.
三维(3D)支架由于其低孔隙率、机械强度以及缺乏细胞与生物活性药物的直接接触而存在巨大局限性。而双膦酸盐药物具有刺激成骨细胞和骨髓间充质干细胞(hMSC)成骨的能力,这吸引了其在治疗方面的应用。然而,它给药困难、生物利用度低且缺乏位点特异性,限制了其使用。所提出的支架结构允许细胞通过在支架界面层相互作用,在其顶端接触生物活性表面。3D聚己内酯(PCL)支架的界面已用包裹在壳聚糖基质中的阿仑膦酸盐修饰的羟基磷灰石(MALD)进行了涂层,以模拟天然环境并刺激细胞与生物活性层的相互作用。其中机械强度将由PCL骨架提供。在MALD复合材料中,羟基磷灰石(HAP)成分将控制阿仑膦酸盐(ALD)的释放行为,并且HAP的存在将促使局部钙离子浓度升高,从而增加hMSC的增殖和分化。结果显示,MALD的释放率为86.28±0.22。对支架结构进行的XPS和SEM研究表明,壳聚糖在界面上有令人鼓舞的颗粒沉积。所有支架在一周多的时间内都增强了细胞黏附、增殖和骨细胞分化,且具有3.03±0.2 kPa的机械强度,无体外细胞毒性。