Functionally Graded Scaffolds Research Articles

Porous Functionally Graded Scaffold prepared by a single-step freeze-drying process. A bioinspired approach for wound care

Nowadays, chronic wounds are the major cause of morbidity worldwide and the healthcare costs related to wound care are a billion-dollar issue; chronic wounds involve a non-healing process that makes necessary the application of advanced wound dressings to promote skin integrity recovery. Functionally Graded Scaffolds (FGSs) are currently driving interest as promising candidates in mimicking the skin tissue environment and, thus, in enhancing a faster and more effective wound healing process. Aim of the present work was to design and develop a porous FGS based on κ-carrageenan (κCG) for the management of chronic skin wounds; a freeze-drying process was optimized to obtain in a single-step a three-layered FGS characterized by a pore size gradient functional to mimic the structure of native skin tissue. In addition to κCG, arginine and whey protein isolate were used as multifunctional agents for FGS preparation; these substances can not only intervene in some stages of wound healing but are able to establish non-covalent interactions with κCG, which were responsible for the production of layers with different pore size, water content capability and mechanical properties. Cell migration, adhesion and proliferation within the FGS structure were evaluated in vitro on fibroblasts and FGS wound healing potential was also studied in vivo on a murine model.

Design and assessment of the biomimetic capabilities of a Voronoi-based cancellous microstructure

Parameterized cellular microstructures allow for the development of efficient multiscale optimization strategies for the design of Functionally Graded Scaffolds (FGSs). This work assesses the biomimetic capabilities of the Voronoi-based cancelous bone microstructure introduced by Fantini et al. (2016) in terms of histomorphometric and elastic properties. Histomorphometric data of 23 bovine bone specimens and elastic data of 140 human bone specimens are used as reference. Based on the key findings that there exists a strong correspondence between the trabecular thickness and the solid volume fraction for natural cancelous bone, and that the stretching of the Voronoi microstructure is an effective means to induce anisotropy, the generative procedure by Fantini et al. (2016) is assessed and tuned to account for anisotropy and elastic properties. It is shown that the resulting mimetic microstructures have histomorphometric features and elastic properties that are in very good accordance to those of the natural samples. The outcomes of this work are a step forward towards the integration of the Voronoi-based microstructure into multiscale design tools.

Biomaterials, Current Strategies, and Novel Nano-Technological Approaches for Periodontal Regeneration.

Periodontal diseases involve injuries to the supporting structures of the tooth and, if left untreated, can lead to the loss of the tooth. Regenerative periodontal therapies aim, ideally, at healing all the damaged periodontal tissues and represent a significant clinical and societal challenge for the current ageing population. This review provides a picture of the currently-used biomaterials for periodontal regeneration, including natural and synthetic polymers, bioceramics (e.g., calcium phosphates and bioactive glasses), and composites. Bioactive materials aim at promoting the regeneration of new healthy tissue. Polymers are often used as barrier materials in guided tissue regeneration strategies and are suitable both to exclude epithelial down-growth and to allow periodontal ligament and alveolar bone cells to repopulate the defect. The problems related to the barrier postoperative collapse can be solved by using a combination of polymeric membranes and grafting materials. Advantages and drawbacks associated with the incorporation of growth factors and nanomaterials in periodontal scaffolds are also discussed, along with the development of multifunctional and multilayer implants. Tissue-engineering strategies based on functionally-graded scaffolds are expected to play an ever-increasing role in the management of periodontal defects.

User interface tool for a novel plasma-assisted bio-additive extrusion system

PurposeThis paper aims to describe the control software of a novel manufacturing system called plasma-assisted bio-extrusion system (PABS), designed to produce complex multi-material and functionally graded scaffolds for tissue engineering applications. This fabrication system combines multiple pressure-assisted and screw-assisted printing heads and plasma jets. Control software allows the users to create single or multi-material constructs with uniform pore size or pore size gradients by changing the operation parameters, such as geometric parameters, lay-down pattern, filament distance, feed rate and layer thickness, and to produce functional graded scaffolds with different layer-by-layer coating/surface modification strategies by using the plasma modification system.Design/methodology/approachMATLAB GUI is used to develop the software, including the design of the user interface and the implementation of all mathematical programing for both multi-extrusion and plasma modification systems.FindingsBased on the user definition, G programing codes are generated, enabling full integration and synchronization with the hardware of PABS. Single, multi-material and functionally graded scaffolds can be obtained by manipulating different materials, scaffold designs and processing parameters. The software is easy to use, allowing the efficient control of the PABS even for the fabrication of complex scaffolds.Originality/valueThis paper introduces a novel additive manufacturing system for tissue engineering applications describing in detail the software developed to control the system. This new fabrication system represents a step forward regarding the current state-of-the-art technology in the field of biomanufacturing, enabling the design and fabrication of more effective scaffolds matching the mechanical and surface characteristics of the surrounding tissue and enabling the incorporation of high number of cells uniformly distributed and the introduction of multiple cell types with positional specificity.

Development of polymeric functionally graded scaffolds: a brief review.

Over recent years, there has been a growing interest in multilayer scaffolds fabrication approaches. In fact, functionally graded scaffolds (FGSs) provide biological and mechanical functions potentially similar to those of native tissues. Based on the final application of the scaffold, there are different properties (physical, mechanical, biochemical, etc.) which need to gradually change in space. Therefore, a number of different technologies have been investigated, and often combined, to customize each region of the scaffolds as much as possible, aiming at achieving the best regenerative performance.In general, FGSs can be categorized as bilayered or multilayered, depending on the number of layers in the whole structure. In other cases, scaffolds are characterized by a continuous gradient of 1 or more specific properties that cannot be related to the presence of clearly distinguished layers. Since each traditional approach presents peculiar advantages and disadvantages, FGSs are good candidates to overcome the limitations of current treatment options. In contrast to the reviews reported in the literature, which usually focus on the application of FGS, this brief review provides an overview of the most common strategies adopted to prepare FGS.

A Facile and Eco-friendly Route to Fabricate Poly(Lactic Acid) Scaffolds with Graded Pore Size

Over the recent years, functionally graded scaffolds (FGS) gaineda crucial role for manufacturing of devices for tissue engineering. The importance of this new field of biomaterials research is due to the necessity to develop implants capable of mimicking the complex functionality of the various tissues, including a continuous change from one structure or composition to another. In this latter context, one topic of main interest concerns the design of appropriate scaffolds for bone-cartilage interface tissue. In this study, three-layered scaffolds with graded pore size were achieved by melt mixing poly(lactic acid) (PLA), sodium chloride (NaCl) and polyethylene glycol (PEG). Pore size distributions were controlled by NaCl granulometry and PEG solvation. Scaffolds were characterized from a morphological and mechanical point of view. A correlation between the preparation method, the pore architecture and compressive mechanical behavior was found. The interface adhesion strength was quantitatively evaluated by using a custom-designed interfacial strength test. Furthermore, in order to imitate the human physiology, mechanical tests were also performed in phosphate buffered saline (PBS) solution at 37 °C. The method herein presented provides a high control of porosity, pore size distribution and mechanical performance, thus offering the possibility to fabricate three-layered scaffolds with tailored properties by following a simple and eco-friendly route.

A Facile and Eco-friendly Route to Fabricate Poly(Lactic Acid) Scaffolds with Graded Pore Size.

Over the recent years, functionally graded scaffolds (FGS) gaineda crucial role for manufacturing of devices for tissue engineering. The importance of this new field of biomaterials research is due to the necessity to develop implants capable of mimicking the complex functionality of the various tissues, including a continuous change from one structure or composition to another. In this latter context, one topic of main interest concerns the design of appropriate scaffolds for bone-cartilage interface tissue. In this study, three-layered scaffolds with graded pore size were achieved by melt mixing poly(lactic acid) (PLA), sodium chloride (NaCl) and polyethylene glycol (PEG). Pore size distributions were controlled by NaCl granulometry and PEG solvation. Scaffolds were characterized from a morphological and mechanical point of view. A correlation between the preparation method, the pore architecture and compressive mechanical behavior was found. The interface adhesion strength was quantitatively evaluated by using a custom-designed interfacial strength test. Furthermore, in order to imitate the human physiology, mechanical tests were also performed in phosphate buffered saline (PBS) solution at 37 °C. The method herein presented provides a high control of porosity, pore size distribution and mechanical performance, thus offering the possibility to fabricate three-layered scaffolds with tailored properties by following a simple and eco-friendly route.

Geometry Design Optimization of Functionally Graded Scaffolds for Bone Tissue Engineering: A Mechanobiological Approach.

Functionally Graded Scaffolds (FGSs) are porous biomaterials where porosity changes in space with a specific gradient. In spite of their wide use in bone tissue engineering, possible models that relate the scaffold gradient to the mechanical and biological requirements for the regeneration of the bony tissue are currently missing. In this study we attempt to bridge the gap by developing a mechanobiology-based optimization algorithm aimed to determine the optimal graded porosity distribution in FGSs. The algorithm combines the parametric finite element model of a FGS, a computational mechano-regulation model and a numerical optimization routine. For assigned boundary and loading conditions, the algorithm builds iteratively different scaffold geometry configurations with different porosity distributions until the best microstructure geometry is reached, i.e. the geometry that allows the amount of bone formation to be maximized. We tested different porosity distribution laws, loading conditions and scaffold Young’s modulus values. For each combination of these variables, the explicit equation of the porosity distribution law–i.e the law that describes the pore dimensions in function of the spatial coordinates–was determined that allows the highest amounts of bone to be generated. The results show that the loading conditions affect significantly the optimal porosity distribution. For a pure compression loading, it was found that the pore dimensions are almost constant throughout the entire scaffold and using a FGS allows the formation of amounts of bone slightly larger than those obtainable with a homogeneous porosity scaffold. For a pure shear loading, instead, FGSs allow to significantly increase the bone formation compared to a homogeneous porosity scaffolds. Although experimental data is still necessary to properly relate the mechanical/biological environment to the scaffold microstructure, this model represents an important step towards optimizing geometry of functionally graded scaffolds based on mechanobiological criteria.

Preparation of three-layered porous PLA/PEG scaffold: relationship between morphology, mechanical behavior and cell permeability

Interface tissue engineering (ITE) is used to repair or regenerate interface living tissue such as for instance bone and cartilage. This kind of tissues present natural different properties from a biological and mechanical point of view. With the aim to imitating the natural gradient occurring in the bone–cartilage tissue, several technologies and methods have been proposed over recent years in order to develop polymeric functionally graded scaffolds (FGS). In this study three-layered scaffolds with a pore size gradient were developed by melt mixing polylactic acid (PLA) and two water-soluble porogen agents: sodium chloride (NaCl) and polyethylene glycol (PEG). Pore dimensions were controlled by NaCl granulometry while PEG solvation created a micropores network within the devices. Scaffolds were characterized from a morphological and mechanical point of view in order to find a correlation between the preparation method, the pore architecture and compressive mechanical behavior. Biological tests were also performed in order to study the effect of pore size gradient on the permeation of different cell lines in co-culture. To imitate the physiological work condition, compressive tests were also performed in phosphate buffered saline (PBS) solution at 37°C. The presented preparation method permitted to prepare three-layered scaffolds with high control of porosity and pore size distribution. Furthermore mechanical behaviors were found to be strongly affected by pore architecture of tested devices as well as the permeation of osteoblast and fibroblast in-vitro.

CFD modelling of a mixing chamber for the realisation of functionally graded scaffolds

Biological tissues are characterised by spatially distributed gradients, intricately linked with functions. It is widely accepted that ideal tissue engineered scaffolds should exhibit similar functional gradients to promote successful tissue regeneration. Focusing on bone, in previous work we proposed simple methods to obtain osteochondral functionally graded scaffolds (FGSs), starting from homogeneous suspensions of hydroxyapatite (HA) particles in gelatin solutions. With the main aim of developing an automated device to fabricate FGSs, this work is focused on designing a stirred tank to obtain homogeneous HA–gelatin suspensions. The HA particles transport within the gelatin solution was investigated through computational fluid dynamics (CFD) modelling. First, the steady-state flow field was solved for the continuous phase only. Then, it was used as a starting point for solving the multi-phase transient simulation. CFD results showed that the proposed tank geometry and setup allow for obtaining a homogeneous suspension of HA micro-particles within the gelatin solution.

Functionally graded PCL/β-TCP biocomposites in a multilayered structure for bone tissue regeneration

Functionally graded (FG) composites consisting of polycaprolactone (PCL) and beta-tricalcium phosphate (β-TCP) particles were fabricated with a multilayered structure using a melt plotter with a two-heating-barrel system. Using this process, the concentration of β-TCP particles varied in each layered strut. Scanning electron microscopy (SEM) and energy dispersive spectroscopy mapping of calcium on the fabricated scaffolds indicated that the β-TCP particles were well distributed in each PCL strut, according to conceptual design. By incorporating β-TCP, the FG-PCL/β-TCP scaffolds had meaningful increases in water absorption (30 % increase) and showed good mechanical properties, although the mechanical properties are slightly low compared to pure PCL/β-TCP composite. We performed biological assessments to evaluate the capability of these FG scaffolds to act as a biomaterial for bone tissue regeneration with osteoblast-like cells (MG63). SEM images of cell-seeded FG scaffolds showed that the concentrated β-TCP struts were affected as good cell attachment/proliferation sites. Additionally, calcium deposition on the FG scaffolds was higher than that of normal scaffolds after 14 days. In particular, we observed high levels of mineralization in the highly concentrated β-TCP struts in the FG scaffolds. Based on these results, we believe that the FG scaffolds having various spatially designed structures with graded properties will be widely applicable for hard tissue engineering applications.

Investigation of the mechanical properties and porosity relationships in selective laser-sintered polyhedral for functionally graded scaffolds

An important requirement for a bone tissue engineering scaffold is a stiffness gradient that mimics that of native bone. Such scaffolds can be achieved by controlling their structure and porosity and are termed functionally graded scaffolds (FGS). Currently, the main challenges in FGS fabrication include the iterative and tedious design process as well as a heavy reliance on the user’s CAD/CAM skills. This work aims to bring automated FGS production a step closer by providing a database that correlates scaffold porosity values and the corresponding compressive stiffness and integrating it into the design process. To achieve this goal, scaffolds with different structural configurations were designed using CASTS (Computer Aided System for Tissue Scaffolds), an in-house developed library system consisting of 13 different polyhedral units that can be assembled into scaffold structures. Polycaprolactone (PCL) was chosen as the scaffold material, while selective laser sintering, a powder-based rapid prototyping or additive manufacturing system was employed to fabricate the scaffolds. Mathematical relations correlating scaffold porosity and compressive stiffness readings were formulated and compiled. In addition, cytotoxicity assessment was conducted to evaluate the toxicity of the fabricated PCL scaffolds. Lastly, a brief demonstration of how the formulated relations are used in the FGS design process is presented.