Effects of ceramic additives and bioactive coatings on the degradation of polylactic acid-based bone scaffolds under hydrolytic conditions.

Polylactic acid (PLA) has been extensively used for the manufacturing of scaffolds in bone tissue engineering applications. Due to the low hydrophilicity and the acidic degradation process of this biomaterial, different strategies have been proposed to increase the biofunctionality of the support structure. The use of ceramic particles is a generally preferred option to increase the osteoconductivity of the base material, while acting as buffers to maintain the pH level of the surroundings tissues. Surface modification is another approach to overcome the limitations of PLA for tissue engineering applications. In this work, the degradation profile of 3D-printed PLA scaffolds containing beta-tricalcium phosphate (ß-TCP) and calcium carbonate (CaCO3 ) particles has been studied under hydrolytic conditions. Composite samples treated with plasma and coated with Aloe vera extracts were also studied to evaluate the effect of this surface modification method. The characterization of the 3D structures included its morphological, calorimetric and mechanical evaluation. According to the results obtained, the proposed composite scaffolds allowed an adequate maintenance of the pH level of the surrounding medium, with no effects observed on the morphology and mechanical properties of these structures. Hence, these samples showed potential to be further investigated as candidates for bone tissue regeneration.

Sheep condyle model evaluation of bone marrow cell concentrate combined with a scaffold for repair of large osteochondral defects.

AIMS: Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone. METHODS: The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety. RESULTS: The results six months postoperatively showed that there were no significant differences in bone regrowth and mineral density between BMC-treated animals and controls. A significant upregulation of messenger RNA (mRNA) for types I and II collagens in the BMC group was observed, but there were no differences in the formation of hyaline-like cartilage between the groups. A trend towards reduced sulphated glycosaminoglycans (sGAG) breakdown was detected in the BMC group but this was not statistically significant. Functional weightbearing was not affected by the inclusion of BMC. CONCLUSION: Our results indicated that the addition of BMC to scaffold is safe and has some potentially beneficial effects on osteochondral-tissue regeneration, but not on the functional endpoint of orthopaedic interest. Cite this article: Bone Joint Res 2021;10(10):677-689.

Comparison of CAD and Voxel-Based Modelling Methodologies for the Mechanical Simulation of Extrusion-Based 3D Printed Scaffolds.

Porous structures are of great importance in tissue engineering. Most scaffolds are 3D printed, but there is no single methodology to model these printed parts and to apply finite element analysis to estimate their mechanical behaviour. In this work, voxel-based and geometry-based modelling methodologies are defined and compared in terms of computational efficiency, dimensional accuracy, and mechanical behaviour prediction of printed parts. After comparing the volumes and dimensions of the models with the theoretical and experimental ones, they are more similar to the theoretical values because they do not take into account dimensional variations due to the printing temperature. This also affects the prediction of the mechanical behaviour, which is not accurate compared to reality, but it makes it possible to determine which geometry is stiffer. In terms of comparison of modelling methodologies, based on process efficiency, geometry-based modelling performs better for simple or larger parts, while voxel-based modelling is more advantageous for small and complex geometries.

Experimental Analysis of the Enzymatic Degradation of Polycaprolactone: Microcrystalline Cellulose Composites and Numerical Method for the Prediction of the Degraded Geometry.

The degradation rate of polycaprolactone (PCL) is a key issue when using this material in Tissue Engineering or eco-friendly packaging sectors. Although different PCL-based composite materials have been suggested in the literature and extensively tested in terms of processability by material extrusion additive manufacturing, little attention has been paid to the influence of the fillers on the mechanical properties of the material during degradation. This work analyses the possibility of tuning the degradation rate of PCL-based filaments by the introduction of microcrystalline cellulose into the polymer matrix. The enzymatic degradation of the composite and pure PCL materials were compared in terms of mass loss, mechanical properties, morphology and infrared spectra. The results showed an increased degradation rate of the composite material due to the presence of the filler (enhanced interaction with the enzymes). Additionally, a new numerical method for the prediction of the degraded geometry was developed. The method, based on the Monte Carlo Method in an iterative process, adjusts the degradation probability according to the exposure of each discretized element to the degradation media. This probability is also amplified depending on the corresponding experimental mass loss, thus allowing a good fit to the experimental data in relatively few iterations.

On the Effectiveness of Oxygen Plasma and Alkali Surface Treatments to Modify the Properties of Polylactic Acid Scaffolds.

Surface modification of 3D-printed PLA structures is a major issue in terms of increasing the biofunctionality and expanding the tissue engineering applications of these parts. In this paper, different exposure times were used for low-pressure oxygen plasma applied to PLA 3D-printed scaffolds. Alkali surface treatments were also evaluated, aiming to compare the modifications introduced on the surface properties by each strategy. Surface-treated samples were characterized through the quantification of carboxyl groups, energy-dispersive X-ray spectroscopy, water contact angle measurements, and differential scanning calorimetry analysis. The change in the surface properties was studied over a two-week period. In addition, an enzymatic degradation analysis was carried out to evaluate the effect of the surface treatments on the degradation profile of the 3D structures. The physicochemical characterization results suggest different mechanism pathways for each type of treatment. Alkali-treated scaffolds showed a higher concentration of carboxyl groups on their surface, which enhanced the enzymatic degradation rate, but were also proven to be more aggressive towards 3D-printed structures. In contrast, the application of the plasma treatments led to an increased hydrophilicity of the PLA surface without affecting the bulk properties. However, the changes on the properties were less steady over time.

Three-dimensional printed polycaprolactone-microcrystalline cellulose scaffolds.

Microcrystalline cellulose (MCC) is proposed in this study as an additive in polycaprolactone (PCL) matrices to obtain three-dimensional (3D) printed scaffolds with improved mechanical and biological properties. Improving the mechanical behavior and the biological performance of polycaprolactone-based scaffolds allows to increase the potential of these structures for bone tissue engineering. Different groups of samples were evaluated in order to analyze the effect of the additive in the properties of the PCL matrix. The concentrations of MCC in the groups of samples were 0, 2, 5, and 10% (w/w). These combinations were subjected to a thermogravimetric analysis in order to evaluate the influence of the additive in the thermal properties of the composites. 3D printed scaffolds were manufactured with a commercial 3D printer based on fused deposition modelling. The operation conditions have been established in order to obtain scaffolds with a 0/90° pattern with pore sizes between 450 and 500 µm and porosity values between 50 and 60%. The mechanical properties of these structures were measured in the compression and flexural modes. The scaffolds containing 2 and 5% MCC have higher flexural and compression elastic modulus, although those containing 10% do not show this reinforcement effect. On the other hand, the proliferation of sheep bone marrow cells on the proposed scaffolds was evaluated over 8 days. The results show that the proliferation is significantly better (p < 0.05) on the group of samples containing 2% MCC. Therefore, these scaffolds (PCL:MCC 98:2) have suitable properties to be further evaluated for bone tissue engineering applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 521-528, 2019.