Percorrer por autor "Bártolo, Paulo J."
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- 3D printing of new biobased unsaturated polyesters by microstereo-thermal-lithographyPublication . Gonçalves, Filipa A. M. M.; Costa, Cátia S. M. F.; Fabela, Inês G. P.; Farinha, Dina; Faneca, Henrique; Simões, Pedro N.; Serra, Arménio C.; Bártolo, Paulo J.; Coelho, Jorge F. J.New micro three-dimensional (3D) scaffolds using biobased unsaturated polyesters (UPs) were prepared by microstereo-thermal-lithography (μSTLG). This advanced processing technique offers indubitable advantages over traditional printing methods. The accuracy and roughness of the 3D structures were evaluated by scanning electron microscopy and infinite focus microscopy, revealing a suitable roughness for cell attachment. UPs were synthesized by bulk polycondensation between biobased aliphatic diacids (succinic, adipic and sebacic acid) and two different glycols (propylene glycol and diethylene glycol) using fumaric acid as the source of double bonds. The chemical structures of the new oligomers were confirmed by proton nuclear magnetic resonance spectra, attenuated total reflectance Fourier transform infrared spectroscopy and matrix assisted laser desorption/ionization-time of flight mass spectrometry. The thermal and mechanical properties of the UPs were evaluated to determine the influence of the diacid/glycol ratio and the type of diacid in the polyester's properties. In addition an extensive thermal characterization of the polyesters is reported. The data presented in this work opens the possibility for the use of biobased polyesters in additive manufacturing technologies as a route to prepare biodegradable tailor made scaffolds that have potential applications in a tissue engineering area.
- Additive manufacturing of tissues and organsPublication . Melchels, Ferry P.W.; Domingos, Marco; Klein, Travis J.; Malda, Jos; Bártolo, Paulo J.; Hutmacher, Dietmar W.Additive manufacturing techniques offer the potential to fabricate organized tissue constructs to repair or replace damaged or diseased human tissues and organs. Using these techniques, spatial variations of cells along multiple axes with high geometric complexity in combination with different biomaterials can be generated. The level of control offered by these computer-controlled technologies to design and fabricate tissues will accelerate our understanding of the governing factors of tissue formation and function. Moreover, it will provide a valuable tool to study the effect of anatomy on graft performance. In this review, we discuss the rationale for engineering tissues and organs by combining computer-aided design with additive manufacturing technologies that encompass the simultaneous deposition of cells and materials. Current strategies are presented, particularly with respect to limitations due to the lack of suitable polymers, and requirements to move the current concepts to practical application.
- Additive manufacturing techniques for scaffold-based cartilage tissue engineeringPublication . Caseiro, Ana Rita; Almeida, Henrique A.; Bártolo, Paulo J.Articular cartilage damage is of great concern as it creates chronic pain and reduction of joint movement, leading to osteoarthritis. In current treatments, the resulting healing tissues lack structural organisation of cartilage and consequently have inferior mechanical properties when compared to native cartilage, therefore being prone to failure. Tissue engineering has long worked on cartilage regeneration and several requirements have been identified for the engineered structures to meet the desired function, by combining biodegradable and biocompatible materials, cells and growth factors, aiming at the production of biological structures closely resembling the native tissue.Within the scaffold based techniques for cartilage tissue production, conventional methods have shown limitations, especially regarding the control over the microstructure and repeatability of the produced constructs. Therefore, additive manufacturing techniques grew popular, allowing for a high level of control over the internal scaffold architecture and external shape of the construct, as well as guaranteeing its reproducibility.
- Advanced Biofabrication Strategies for Skin Regeneration and RepairPublication . Pereira, Rúben F.; Barrias, Cristina C; Granja, Pedro L; Bártolo, Paulo J.Skin is the largest organ of human body, acting as a barrier with protective, immunologic and sensorial functions. Its permanent exposure to the external environment can result in different kinds of damage with loss of variable volumes of extracellular matrix. For the treatment of skin lesions, several strategies are currently available, such as the application of autografts, allografts, wound dressings and tissue-engineered substitutes. Although proven clinically effective, these strategies are still characterized by key limitations such as patient morbidity, inadequate vascularization, low adherence to the wound bed, the inability to reproduce skin appendages and high manufacturing costs. Advanced strategies based on both bottom-up and top-down approaches offer an effective, permanent and viable alternative to solve the abovementioned drawbacks by combining biomaterials, cells, growth factors and advanced biomanufacturing techniques. This review details recent advances in skin regeneration and repair strategies, and describes their major advantages and limitations. Future prospects for skin regeneration are also outlined.
- Cell Therapy with Human MSCs Isolated from the Umbilical Cord Wharton Jelly Associated to a PVA Membrane in the Treatment of Chronic Skin WoundsPublication . Ribeiro, Jorge; Pereira, Tiago; Amorim, Irina; Caseiro, Ana Rita; Lopes, Maria A.; Lima, Joana; Gartner, Andrea; Domingos Santos, José Domingos; Bártolo, Paulo J.; Rodrigues, Jorge Manuel; Mauricio, Ana Colette; Luís, Ana LúciaThe healing process of the skin is a dynamic procedure mediated through a complex feedback of growth factors secreted by a variety of cells types. Despite the most recent advances in wound healing management and surgical procedures, these techniques still fail up to 50%, so cellular therapies involving mesenchymal stem cells (MSCs) are nowadays a promising treatment of skin ulcers which are a cause of high morbidity. The MSCs modulate the inflammatory local response and induce cell replacing, by a paracrine mode of action, being an important cell therapy for the impaired wound healing. The local application of human MSCs (hMSCs) isolated from the umbilical cord Wharton's jelly together with a poly(vinyl alcohol) hydrogel (PVA) membrane, was tested to promote wound healing in two dogs that were referred for clinical examination at UPVET Hospital, showing non-healing large skin lesions by the standard treatments. The wounds were infiltrated with 1000 cells/µl hMSCs in a total volume of 100 µl per cm2 of lesion area. A PVA membrane was applied to completely cover the wound to prevent its dehydration. Both animals after the treatment demonstrated a significant progress in skin regeneration with decreased extent of ulcerated areas confirmed by histological analysis. The use of Wharton's jelly MSCs associated with a PVA membrane showed promising clinical results for future application in the treatment of chronic wounds in companion animals and humans.
- Cell-instructive pectin hydrogels crosslinked via thiol-norbornene photo-click chemistry for skin tissue engineeringPublication . Pereira, Rúben; Barrias, Cristina C.; Bártolo, Paulo J.; Granja, Pedro L.Cell-instructive hydrogels are attractive for skin repair and regeneration, serving as interactive matrices to promote cell adhesion, cell-driven remodeling and de novo deposition of extracellular matrix compo nents. This paper describes the synthesis and photocrosslinking of cell-instructive pectin hydrogels using cell-degradable peptide crosslinkers and integrin-specific adhesive ligands. Protease-degradable hydro gels obtained by photoinitiated thiol-norbornene click chemistry are rapidly formed in the presence of dermal fibroblasts, exhibit tunable properties and are capable of modulating the behavior of embedded cells, including the cell spreading, hydrogel contraction and secretion of matrix metalloproteases. Keratinocytes seeded on top of fibroblast-loaded hydrogels are able to adhere and form a compact and dense layer of epidermis, mimicking the architecture of the native skin. Thiol-ene photocrosslinkable pec tin hydrogels support the in vitro formation of full-thickness skin and are thus a highly promising plat form for skin tissue engineering applications, including wound healing and in vitro testing mod
- Collagen surface modified poly(ε-caprolactone) scaffolds with improved hydrophilicity and cell adhesion propertiesPublication . Sousa, Inês; Mendes, Ausenda; Pereira, Rúben F.; Bártolo, Paulo J.Poly(ε-caprolactone) (PCL)/collagen scaffolds were produced using a four-step procedure comprising (i) the fabrication of PCL scaffolds through an additive bioextrusion system, (ii) the PCL surface modification using a plasma treatment, (iii) the acrylic acid (AAc) grafting by ultraviolet (UV) polymerization, and (iv) the immobilization of collagen into the scaffold surface through the carbodiimide chemistry. This procedure allowed the quick fabrication of highly porous scaffolds with interconnected pores, well-defined internal architecture and improved cell adhesion properties. The immobilization of collagen into the PCL surface led to a significant enhancement in the hydrophilicity, while the biological tests showed a further improvement in the adhesion of fibroblast cells. These results indicate that the collagen surface modification is an effective strategy to render the hydrophobic nature of PCL and overcome the limited cell interaction of 3D PCL scaffolds.
- Combined Elastic and Shear Stress Solicitations for Topological Optimisation of Micro-CT Based ScaffoldsPublication . Almeida, Henrique A.; Bártolo, Paulo J.Advanced additive manufacturing technologies, namely Biomanufacturing, are being used to fabricate scaffolds with controlled architecture for tissue engineering applications. These technologies combined with computer-aided design (CAD) enable to produce three-dimensional structures layer-by-layer in a multitude of biomaterials. Actual prediction of the effective mechanical properties of scaffolds produced by Biomanufacturing, is very important for tissue engineering applications. A novel computer based technique for scaffold design is topological optimisation. Topological optimisation is a form of "shape" optimisation, usually referred to as "layout" optimisation. The goal of topological optimisation is to find the best use of material for a body that is subjected to either a single load or a multiple load distribution. In this research work, a topological optimization strategy is presented to find out the best material use for a construct subject to either a single load or a multiple load distribution, maximising its mechanical behaviour under tensile and shear stress solicitations. The proposed topological optimization scheme enables the design of ideal topological architectures based on existing biologic Micro-CT data for the design of biomimetic scaffolds.
- Degradation Behavior of Biopolymer-based Membranes for Skin Tissue RegenerationPublication . Pereira, Rúben F.; Bártolo, Paulo J.This research work investigates the long term in vitro degradation behavior of alginate-aloe vera composite membranes for skin regeneration. The membranes were prepared through a two-step procedure, which involves the synthesis of thin membranes and the crosslinking reaction. Degradation tests were performed through the immersion of the membranes into simulated body fluid solution at pH 7.4 and physiological temperature, during 6 months. Alginate-aloe vera membranes are resistant to the hydrolytic degradation and exhibit weight loss values in a range of 20.37-26.32%. Results show that an increase in the aloe vera content leads to a slight increase in the weight loss during the degradation process. Preliminary drug release studies, using nitrofurazone as a model drug, suggest the ability of the developed membranes to be used as a drug delivery system.
- Design of tissue engineering scaffolds based on hyperbolic surfaces: Structural numerical evaluationPublication . Almeida, Henrique A.; Bártolo, Paulo J.Tissue engineering represents a new field aiming at developing biological substitutes to restore, maintain, or improve tissue functions. In this approach, scaffolds provide a temporary mechanical and vascular support for tissue regeneration while tissue in-growth is being formed. These scaffolds must be biocompatible, biodegradable, with appropriate porosity, pore structure and distribution, and optimal vascularization with both surface and structural compatibility. The challenge is to establish a proper balance between porosity and mechanical performance of scaffolds.This work investigates the use of two different types of triple periodic minimal surfaces, Schwarz and Schoen, in order to design better biomimetic scaffolds with high surface-to-volume ratio, high porosity and good mechanical properties. The mechanical behaviour of these structures is assessed through the finite element method software Abaqus. The effect of two parametric parameters (thickness and surface radius) is also evaluated regarding its porosity and mechanical behaviour.