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This study intended to design novel nanofibrillated cellulose/cyclodextrin-based 3D scaffolds loaded with raloxifene hydrochloride for bone regeneration. The scaffolds were prepared using two different types of cyclodextrins namely; beta-cyclodextrin and methyl-beta-cyclodextrin. The prepared scaffolds were evaluated by characterizing their porosity, compressive strength, in-vitro drug release, FT-IR and XRD as well as their morphological properties using SEM. Results presented that the prepared scaffolds were highly porous, additionally, the scaffold containing drug/beta-cyclodextrin kneaded complex (SC5) showed the most controlled drug release pattern with the least burst effect and reached almost complete release at 480 h. The in-vitro cytocompatibility and regenerative effect of the chosen scaffold (SC5) was assessed using Saos-2 cell line. Results proved that SC5 was biocompatible. Moreover, it enhanced the cell adhesion, alkaline phosphatase enzyme expression and calcium ion deposition which are essential factors for bone mineralization. The obtained observations presented a novel, safe and propitious approach for bone engineering., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Nanofibrillated cellulose, obtained from rice straw agricultural wastes was used as a substrate for the preparation of a new injectable and mineralized hydrogel for bone regeneration. Tetramethyl pyridine oxyl (TEMPO) oxidized nanofibrillated cellulose, was mineralized through the incorporation of a prepared and characterized biphasic calcium phosphate at a fixed ratio of 50 wt%. The TEMPO-oxidized rice straw nanofibrillated cellulose was characterized using transmission electron microscopy, Fourier transform infrared, and carboxylic content determination. The injectability and viscosity of the prepared hydrogel were evaluated using universal testing machine and rheometer testing, respectively. Cytotoxicity and alkaline phosphatase level tests on osteoblast like-cells for in vitro assessment of the biocompatibility were investigated. Results revealed that the isolated rice straw nanofibrillated cellulose is a nanocomposite of the cellulose nanofibers and silica nanoparticles. Rheological properties of the tested materials are suitable for use as injectable material and of nontoxic effect on osteoblast-like cells, as revealed by the positive alkaline phosphate assay. However, nanofibrillated cellulose/ biphasic calcium phosphate hydrogel showed higher cytotoxicity and lower bioactivity test results when compared to that of nanofibrillated cellulose.

In this paper we explore the use of native bacterial cellulose (BC) in combination with functionalized multi-walled carbon nanotubes (MWNTs) as an original biomaterial, suitable three-dimensional (3D) scaffold for osteoblastic cell culture. Functionalized MWNTs were mixed with native BC (secreted by Gluconacetobacter xylinus) with the aim of reinforcing the mechanical properties of BC. The results indicate that BC-MWNTs scaffolds support osteoblast viability, adhesion and proliferation at higher levels as compared to traditional culture substrates. Chemically functionalized MWNTs are also an excellent material to be used as scaffold because these did not affect cell viability and showed an enhanced osteoblast adhesion. These results suggest the potential for this combination of biomaterials, i.e. BC and carbon nanomaterials, as scaffolds for bone regeneration., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study reports the development of biological/synthetic scaffolds for bone tissue engineering (TE) via 3D bioplotting. These scaffolds were composed of poly(L-lactic-co-glycolic acid) (PLGA), type I collagen, and nano-hydroxyapatite (nHA) in an attempt to mimic the extracellular matrix of bone. The solvent used for processing the scaffolds was 1,1,1,3,3,3-hexafluoro-2-propanol. The produced scaffolds were characterized by scanning electron microscopy, microcomputed tomography, thermogravimetric analysis, and unconfined compression test. This study also sought to validate the use of finite-element optimization in COMSOL Multiphysics for scaffold design. Scaffold topology was simplified to three factors: nHA content, strand diameter, and strand spacing. These factors affect the ability of the scaffold to bear mechanical loads and how porous the structure can be. Twenty four scaffolds were constructed according to an I-optimal, split-plot designed experiment (DE) in order to generate experimental models of the factor-response relationships. Within the design region, the DE and COMSOL models agreed in their recommended optimal nHA (30%) and strand diameter (460 μm). However, the two methods disagreed by more than 30% in strand spacing (908 μm for DE; 601 μm for COMSOL). Seven scaffolds were 3D-bioplotted to validate the predictions of DE and COMSOL models (4.5-9.9 MPa measured moduli). The predictions for these scaffolds showed relative agreement for scaffold porosity (mean absolute percentage error of 4% for DE and 13% for COMSOL), but were substantially poorer for scaffold modulus (51% for DE; 21% for COMSOL), partly due to some simplifying assumptions made by the models. Expanding the design region in future experiments (e.g., higher nHA content and strand diameter), developing an efficient solvent evaporation method, and exerting a greater control over layer overlap could allow developing PLGA-nHA-collagen scaffolds to meet the mechanical requirements for bone TE.

The aim of this study was to evaluate the in vitro osteogenic effects and in vivo new bone formation of three-dimensional (3D) printed alendronate (Aln)-releasing poly(caprolactone) (PCL) (Aln/PCL) scaffolds in rat tibial defect models. 3D printed Aln/PCL scaffolds were fabricated via layer-by-layer deposition. The fabricated Aln/PCL scaffolds had high porosity and an interconnected pore structure and showed sustained Aln release. In vitro studies showed that MG-63 cells seeded on the Aln/PCL scaffolds displayed increased alkaline phosphatase (ALP) activity and calcium content in a dose-dependent manner when compared with cell cultures in PCL scaffolds. In addition, in vivo animal studies and histologic evaluation showed that Aln/PCL scaffolds implanted in a rat tibial defect model markedly increased new bone formation and mineralized bone tissues in a dose-dependent manner compared to PCL-only scaffolds. Our results show that 3D printed Aln/PCL scaffolds are promising templates for bone tissue engineering applications.