Functionalized hydrogels as smart gene delivery systems to treat musculoskeletal disorders

Despite critical advances in regenerative medicine, the generation of definitive, reliable treatments for musculoskeletal diseases remains challenging. Gene therapy based on the delivery of therapeutic genetic sequences has strong value to offer effective, durable options to decisively manage such disorders. Furthermore, scaffoldmediated gene therapy provides powerful alternatives to overcome hurdles associated with classical gene therapy, allowing for the spatiotemporal delivery of candidate genes to sites of injury. Among the many scaffolds for musculoskeletal research, hydrogels raised increasing attention in addition to other potent systems (solid, hybrid scaffolds) due to their versatility and competence as drug and cell carriers in tissue engineering and wound dressing. Attractive functionalities of hydrogels for musculoskeletal therapy include their injectability, stimuli-responsiveness, self-healing, and nanocomposition that may further allow to upgrade of them as “intelligently” efficient and mechanically strong platforms, rather than as just inert vehicles. Such functionalized hydrogels may also be tuned to successfully transfer therapeutic genes in a minimally invasive manner in order to protect their cargos and allow for their long-term effects. In light of such features, this review focuses on functionalized hydrogels and demonstrates their competence for the treatment of musculoskeletal disorders using gene therapy procedures, from gene therapy principles to hydrogel functionalization methods and applications of hydrogel-mediated gene therapy for musculoskeletal disorders, while remaining challenges are being discussed in the perspective of translation in patients. Statement of significance: Despite advances in regenerative medicine, the generation of definitive, reliable treatments for musculoskeletal diseases remains challenging. Gene therapy has strong value in offering effective, durable options to decisively manage such disorders. Scaffold-mediated gene therapy provides powerful alternatives to overcome hurdles associated with classical gene therapy. Among many scaffolds for musculoskeletal research, hydrogels raised increasing attention. Functionalities including injectability, stimuli-responsiveness, and self-healing, tune them as “intelligently” efficient and mechanically strong platforms, rather than as just inert vehicles. This review introduces functionalized hydrogels for musculoskeletal disorder treatment using gene therapy procedures, from gene therapy principles to functionalized hydrogels and applications of hydrogelmediated gene therapy for musculoskeletal disorders, while remaining challenges are discussed from the perspective of translation in patients

Uso de gliricídia (Gliricidia sepium (Jacq.) Steud) em sistema alley cropping na produção de macaxeira (Manihot esculenta Crantz)

The goal of this study was to verify the influence of quickstick (Gliricidia sepium (Jacq.) Steud) in ally cropping systems for the production of cassava (Manihot esculenta Crantz) in an experimental unit in Santarém, Pará, Northern Brazil. The experiment was carried out in interspersed blocks divided into two treatments with four repetitions each. The massava crop was collected after 8 months, when the number of living plants, the number of roots per plant and the weight of roots per parcel were quantified. The productivity of cassava cultivated in association with quickstick was equal to 2.3 t/ha versus 1.2 t/ha in the control treatment, considering the experimental conditions. The production of roots reached the best results in massava crops using fertilization with quickstick even though no statistical differences were reported among treatments. Therefore, further evaluation based on increased sampling is recommended to provide a more comprehensive dataset.El objetivo fue verificar la influencia del uso de gliricídia (Gliricidia sepium (Jacq.) Steud) en un sistema de cultivo em franjas en la producción de yuca (Manihot esculenta Crantz) en una unidad experimental en Santarém, Pará. El experimento se llevó a cabo en un diseño completamente al azar, con 2 tratamientos, distribuidos en 4 repeticiones. Después de 8 meses de plantado, se cosechó el árbol de yuca, cuantificando el número de plantas vivas, el número de raíces por planta y el peso de raíces por parcela. Los resultados demuestran que la productividad de la yuca con gliricídia fue de 2,3 t/ha, mientras que en el testigo fue de 1,2 t/ha, en las condiciones expuestas en este experimento. La producción de raíces mostró el mejor resultado del cultivo de yuca bajo abono verde con gliricídia, aun sin mostrar diferencia estadística entre tratamientos. Por lo tanto, con el objetivo de una mayor cobertura de datos, se sugiere redimensionar la muestra para futuras evaluaciones. Objetivou-se verificar a influência do uso da gliricídia (Gliricidia sepium (Jacq.) Steud) em sistema alley cropping na produção de macaxeira (Manihot esculenta Crantz) em unidade experimental em Santarém, Pará. O experimento foi conduzido em delineamento inteiramente casualizado, com 2 tratamentos, distribuídos em 4 repetições. Após 8 meses de plantio, foi realizada a colheita da macaxeira, quantificando-se o número de plantas vivas, o número de raízes por planta e o peso de raízes por parcela.  Os resultados denotam que a produtividade de macaxeira com gliricídia foi de 2,3 t/ha, enquanto na testemunha foi de 1,2 t/ha, nas condições expostas neste experimento. A produção de raízes apresentou o melhor resultado da cultura da macaxeira sob a adubação verde com gliricídia, mesmo não apresentando diferença estatística entre tratamentos. Portanto, visando maior abrangência dos dados, sugere-se o redimensionamento da amostragem para as futuras avaliações

Fatigue behaviour of FDM-3D printed polymers, polymeric composites and architected cellular materials

Polymer-based materials are increasingly produced through fused deposition modelling (FDM) – an additive manufacturing process, due to its intrinsic advantages in manufacturing complex shapes and structures at low overhead costs. The versatility of this technology has attracted several industries to print complex geometrical structures. This underlines the importance of studying the mechanical strength of FDM printed polymeric materials, especially their fatigue behaviour in cyclic loading conditions. Conventionally manufactured polymeric materials (e.g. injection moulding) have superior fatigue performance than FDM printed materials. Unlike conventionally manufactured polymers, FDM-made polymers have layer by layer adhesion and the influence of printing parameters make fatigue analysis complex and critical. The influences of printing parameters and printing material characteristics have a significant impact on the fatigue behaviour of these materials. The underlying mechanism behind the fatigue of FDM printed polymers is crucial for the assessment of these materials in structural applications. However, the fatigue behaviour of FDM printed polymeric materials has not been reviewed in detail. Therefore, this article aims to evaluate 3D printed polymeric materials’ fatigue properties. The importance of fatigue in the FDM printed biomedical materials is also reviewed, and more importantly, the novel FDM printed architected cellular material fatigue properties are also introduced. © 2020 The Author(s

Advanced Hydrogels for Cartilage Tissue Engineering: Recent Progress and Future Directions

Cartilage is a tension- and load-bearing tissue and has a limited capacity for intrinsic self-healing. While microfracture and arthroplasty are the conventional methods for cartilage repair, these methods are unable to completely heal the damaged tissue. The need to overcome the restrictions of these therapies for cartilage regeneration has expanded the field of cartilage tissue engineering (CTE), in which novel engineering and biological approaches are introduced to accelerate the development of new biomimetic cartilage to replace the injured tissue. Until now, a wide range of hydrogels and cell sources have been employed for CTE to either recapitulate microenvironmental cues during a new tissue growth or to compel the recovery of cartilaginous structures via manipulating biochemical and biomechanical properties of the original tissue. Towards modifying current cartilage treatments, advanced hydrogels have been designed and synthesized in recent years to improve network crosslinking and self-recovery of implanted scaffolds after damage in vivo. This review focused on the recent advances in CTE, especially self-healing hydrogels. The article firstly presents the cartilage tissue, its defects, and treatments. Subsequently, introduces CTE and summarizes the polymeric hydrogels and their advances. Furthermore, characterizations, the advantages, and disadvantages of advanced hydrogels such as multi-materials, IPNs, nanomaterials, and supramolecular are discussed. Afterward, the self-healing hydrogels in CTE, mechanisms, and the physical and chemical methods for the synthesis of such hydrogels for improving the reformation of CTE are introduced. The article then briefly describes the fabrication methods in CTE. Finally, this review presents a conclusion of prevalent challenges and future outlooks for self-healing hydrogels in CTE applications

The Effect of Carbon Black on the Properties of Plasticised Wheat Gluten Biopolymer

Wheat gluten biopolymers generally become excessively rigid when processed without plasticisers, while the use of plasticisers, on the other hand, can deteriorate their mechanical properties. As such, this study investigated the effect of carbon black (CB) as a filler into glycerol-plasticised gluten to prepare gluten/CB biocomposites in order to eliminate the aforementioned drawback. Thus, biocomposites were manufactured using compression moulding followed by the determination of their mechanical, morphological, and chemical properties. The filler content of 4 wt% was found to be optimal for achieving increased tensile strength by 24%, and tensile modulus by 268% along with the toughness retention based on energy at break when compared with those of glycerol-plasticised gluten. When reaching the filler content up to 6 wt%, the tensile properties were found to be worsened, which can be ascribed to excessive agglomeration of carbon black at the high content levels within gluten matrices. Based on infrared spectroscopy, the results demonstrate an increased amount of beta -sheets, suggesting the formation of more aggregated protein networks induced by increasing the filler contents. However, the addition of fillers did not improve fire and water resistance in such bionanocomposites owing to the high blend ratio of plasticiser to gluten

Circular economy in biocomposite development: State-of-the-art, challenges and emerging trends

Biocomposites being environmentally-friendly alternative to synthetic composites are gaining increasing demand for various applications. Hence, biocomposite development should be integrated within a circular economy (CE) model to ensure a sustainable production that is simultaneously innocuous towards the environment. This review presents an overview of the state-of-the-art technologies for the adoption of the CE concept in biocomposite development. The study outlined the properties, environmental and economic impacts of biocomposites. A critical review of the life-cycle assessment of biocomposite for evaluating greenhouse gas emissions and carbon footprints was conducted. In addition, the opportunities and challenges pertaining to the implementation of CE have been discussed in detail. Recycling and utilisation of bio-based constituents were identified as the critical factors in embracing CE. Therefore, the development of innovative recycling technologies and an enhanced use of novel biocomposite constituents could lead to a reduction in material waste and environmental footprints. This article is one of the first studies to review the circularity of biocomposites in detail that will stimulate further research in enhancing the sustainability of these polymeric materials. © 202

DEVELOPMENT OF MORINGA OLEIFERA LAM. SEEDLINGS IN DIFFERENT SUBSTRATES

Moringa oleifera Lam., known as Moringa, is an arboreal plant belonging to the Moringaceae family, native to India, and has a high capacity to adapt to climatic conditions and arid soils. In this study we evaluated the initial development of seedlings of Moringa oleifera Lam. under different substrates conditions. The experiment was conducted in a completely randomized design, consisting of eight treatments resulting from combinations of the base substrate (85% soil, 3% carbonized rice straw and 12% coconut fiber).  At 60 days after sowing, plant height, stem diameter, dry mass of the aerial part and root system, total dry mass were evaluated, in addition to the Dickson quality index (IQD). The best seedling growth occurred using the combination of 20% poultry litter and 10% bovine manure.  Seedlings produced with substrates formulated with 20% poultry litter and 10% bovine manure showed gains in the evaluated variables, which could be a viable alternative for the production of moringa seedlings

Engineering next-generation bioinks with nanoparticles: moving from reinforcement fillers to multifunctional nanoelements

The application of additive manufacturing in the biomedical field has become a hot topic in the last decade owing to its potential to provide personalized solutions for patients. Different bioinks have been designed trying to obtain a unique concoction that addresses all the needs for tissue engineering and drug delivery purposes, among others. Despite the remarkable progress made, the development of suitable bioinks which combine printability, cytocompatibility, and biofunctionality is still a challenge. In this sense, the well-established synthetic and functionalization routes to prepare nanoparticles with different functionalities make them excellent candidates to be combined with polymeric systems in order to generate suitable multi-functional bioinks. In this review, we briefly discuss the most recent advances in the design of functional nanocomposite hydrogels considering their already evaluated or potential use as bioinks. The scientific development over the last few years is reviewed, focusing the discussion on the wide range of functionalities that can be incorporated into 3D bioprinted constructs through the addition of multifunctional nanoparticles in order to increase their regenerative potential in the field of tissue engineering.Authors acknowledge financial support from the ERC Grant CoG MagTendon nr 772817; FCT – Fundação para a Ciência e a Tecnologia for the PhD grant of SMB (PD/BD/129403/2017), for the contract to MGF (CEECIND/01375/2017); and for project SmarTendon (PTDC/NAN-MAT/30595/2017). AP is grateful to Xunta de Galicia for his postdoctoral grant ED481B2019/025. Some figures were created with BioRender.com