Hybrid scaffolds for bone tissue engineering: Integration of composites and bioactive hydrogels loaded with hDPSCs.

Bone tissue regeneration remains a significant challenge in clinical settings due to the complexity of replicating the mechanical and biological properties of bone environment. This study addresses this challenge by proposing a hybrid scaffold designed to enhance both bioactivity and physical stability for bone tissue regeneration. This research is the fisrt to develop a rigid 3D structure composed of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) integrated with a bioink containing human dental pulp stem/stromal cells (hDPSCs), alginate, nHA and collagen (Col). The biofabricated constructs were extensively characterized through cytocompatibility tests, osteogenic differentiation assessment, and biocompatibility evaluation in a rat model. In vitro results demontrated that the hybrid scaffolds presented significantly higher cell viability after 168 h compared to the control group. Furthermore, the hybrid scaffolds showed increased osteogenic differentiation relative to other groups. In vivo evaluation indicated good biocompatibility, characterized by minimal inflammatory response and successful tissue integration. These findings highlight the scaffold's potential to support bone tissue regeneration by combining the mechanical strength of PCL and nHA with the biological activity of the alginate-nHA-Col and hDPSCs bioink. The current study provides a promising foundation for the development of biomaterials aimed at improving clinical outcomes in bone repair and regeneration, particulary for the treatment of critical-size bone defects, targeted drug administration, and three-dimensional models for bone tissue engineering.

Recycling Ophthalmic Lens Wastewater in a Circular Economy Context: A Case Study with Microalgae Integration.

Water pollution poses a global threat to ecosystems and human health and is driven by the presence of various contaminants in wastewater, including nano- and microplastics. Despite the magnitude of this problem, the majority of global wastewater is released untreated into water bodies. To combat this issue, a multi-strategy approach is needed. This study explores a circular economy-based solution for treating emerging pollutants, particularly wastewater from ophthalmic spectacle lens production. Our approach integrates solid waste materials into polymeric and cement matrices while also utilising wastewater for microalgae cultivation. This innovative strategy focuses on biomass generation and economic valorisation. By adopting a circular economy model, we aim to transform environmental pollutants from wastewater into valuable organic products. A key component of our approach is the utilisation of microalgae, specifically Nannochloropsis sp., known for its high lipid content and resilience. This microalgae species serves as a promising biobased feedstock, supporting the production of innovative biobased products, such as biopolymers, for ophthalmic lens manufacturing. Our interdisciplinary approach combines microalgae technology, analytical chemistry, cement production, and polymer processing to develop a sustainable circular economy model that not only addresses environmental concerns, but also offers economic benefits. This study underscores the potential of harnessing high-value products from waste streams and underscores the importance of circular economy principles in tackling pollution and resource challenges.

Assessment of 3D-Printed Polycaprolactone, Hydroxyapatite Nanoparticles and Diacrylate Poly(ethylene glycol) Scaffolds for Bone Regeneration.

Notwithstanding the advances achieved in the last decades in the field of synthetic bone substitutes, the development of biodegradable 3D-printed scaffolds with ideal mechanical and biological properties remains an unattained challenge. In the present work, a new approach to produce synthetic bone grafts that mimic complex bone structure is explored. For the first time, three scaffolds of various composition, namely polycaprolactone (PCL), PCL/hydroxyapatite nanoparticles (HANp) and PCL/HANp/diacrylate poly(ethylene glycol) (PEGDA), were manufactured by extrusion. Following the production and characterisation of the scaffolds, an in vitro evaluation was carried out using human dental pulp stem/stromal cells (hDPSCs). Through the findings, it was possible to conclude that, in all groups, the scaffolds were successfully produced presenting networks of interconnected channels, adequate porosity for migration and proliferation of osteoblasts (approximately 50%). Furthermore, according to the in vitro analysis, all groups were considered non-cytotoxic in contact with the cells. Nevertheless, the group with PEGDA revealed hydrophilic properties (15.15° ± 4.06) and adequate mechanical performance (10.41 MPa ± 0.934) and demonstrated significantly higher cell viability than the other groups analysed. The scaffolds with PEGDA suggested an increase in cell adhesion and proliferation, thus are more appropriate for bone regeneration. To conclude, findings in this study demonstrated that PCL, HANp and PEGDA scaffolds may have promising effects on bone regeneration and might open new insights for 3D tissue substitutes.

Gamma Irradiation Processing on 3D PCL Devices-A Preliminary Biocompatibility Assessment.

Additive manufacturing or 3D printing applying polycaprolactone (PCL)-based medical devices represents an important branch of tissue engineering, where the sterilization method is a key process for further safe application in vitro and in vivo. In this study, the authors intend to access the most suitable gamma radiation conditions to sterilize PCL-based scaffolds in a preliminary biocompatibility assessment, envisioning future studies for airway obstruction conditions. Three radiation levels were considered, 25 kGy, 35 kGy and 45 kGy, and evaluated as regards their cyto- and biocompatibility. All three groups presented biocompatible properties, indicating an adequate sterility condition. As for the cytocompatibility analysis, devices sterilized with 35 kGy and 45 kGy showed better results, with the 45 kGy showing overall improved outcomes. This study allowed the selection of the most suitable sterilization condition for PCL-based scaffolds, aiming at immediate future assays, by applying 3D-customized printing techniques to specific airway obstruction lesions of the trachea.

Additive Manufactured Poly(ε-caprolactone)-graphene Scaffolds: Lamellar Crystal Orientation, Mechanical Properties and Biological Performance.

Understanding the mechano-biological coupling mechanisms of biomaterials for tissue engineering is of major importance to assure proper scaffold performance in situ. Therefore, it is of paramount importance to establish correlations between biomaterials, their processing conditions, and their mechanical behaviour, as well as their biological performance. With this work, it was possible to infer a correlation between the addition of graphene nanoparticles (GPN) in a concentration of 0.25, 0.5, and 0.75% (w/w) (GPN0.25, GPN0.5, and GPN0.75, respectively) in three-dimensional poly(ε-caprolactone) (PCL)-based scaffolds, the extrusion-based processing parameters, and the lamellar crystal orientation through small-angle X-ray scattering experiments of extruded samples of PCL and PCL/GPN. Results revealed a significant impact on the scaffold's mechanical properties to a maximum of 0.5% of GPN content, with a significant improvement in the compressive modulus of 59 MPa to 93 MPa. In vitro cell culture experiments showed the scaffold's ability to support the adhesion and proliferation of L929 fibroblasts (fold increase of 28, 22, 23, and 13 at day 13 (in relation to day 1) for PCL, GPN0.25, GPN0.5, and GPN0.75, respectively) and bone marrow mesenchymal stem/stromal cells (seven-fold increase for all sample groups at day 21 in relation to day 1). Moreover, the cells maintained high viability, regular morphology, and migration capacity in all the different experimental groups, assuring the potential of PCL/GPN scaffolds for tissue engineering (TE) applications.

3D Printed Poly(𝜀-caprolactone)/Hydroxyapatite Scaffolds for Bone Tissue Engineering: A Comparative Study on a Composite Preparation by Melt Blending or Solvent Casting Techniques and the Influence of Bioceramic Content on Scaffold Properties.

Bone tissue engineering has been developed in the past decades, with the engineering of bone substitutes on the vanguard of this regenerative approach. Polycaprolactone-based scaffolds are fairly applied for bone regeneration, and several composites have been incorporated so as to improve the scaffolds' mechanical properties and tissue in-growth. In this study, hydroxyapatite is incorporated on polycaprolactone-based scaffolds at two different proportions, 80:20 and 60:40. Scaffolds are produced with two different blending methods, solvent casting and melt blending. The prepared composites are 3D printed through an extrusion-based technique and further investigated with regard to their chemical, thermal, morphological, and mechanical characteristics. In vitro cytocompatibility and osteogenic differentiation was also assessed with human dental pulp stem/stromal cells. The results show the melt-blending-derived scaffolds to present more promising mechanical properties, along with the incorporation of hydroxyapatite. The latter is also related to an increase in osteogenic activity and promotion. Overall, this study suggests polycaprolactone/hydroxyapatite scaffolds to be promising candidates for bone tissue engineering, particularly when produced by the MB method.

Fabrication of Poly(ε-caprolactone) Scaffolds Reinforced with Cellulose Nanofibers, with and without the Addition of Hydroxyapatite Nanoparticles.

Biomaterial properties and controlled architecture of scaffolds are essential features to provide an adequate biological and mechanical support for tissue regeneration, mimicking the ingrowth tissues. In this study, a bioextrusion system was used to produce 3D biodegradable scaffolds with controlled architecture, comprising three types of constructs: (i) poly(ε-caprolactone) (PCL) matrix as reference; (ii) PCL-based matrix reinforced with cellulose nanofibers (CNF); and (iii) PCL-based matrix reinforced with CNF and hydroxyapatite nanoparticles (HANP). The effect of the addition and/or combination of CNF and HANP into the polymeric matrix of PCL was investigated, with the effects of the biomaterial composition on the constructs (morphological, thermal, and mechanical performances) being analysed. Scaffolds were produced using a single lay-down pattern of 0/90°, with the same processing parameters among all constructs being assured. The performed morphological analyses showed a satisfactory distribution of CNF within the polymer matrix and high reliability was obtained among the produced scaffolds. Significant effects on surface wettability and thermal properties were observed, among scaffolds. Regarding the mechanical properties, higher scaffold stiffness in the reinforced scaffolds was obtained. Results from the cytotoxicity assay suggest that all the composite scaffolds presented good biocompatibility. The results of this first study on cellulose and hydroxyapatite reinforced constructs with controlled architecture clearly demonstrate the potential of these 3D composite constructs for cell cultivation with enhanced mechanical properties.