Laminarin is a low-molecular-weight (<10 kDa) glucan found in brown algae made up of β(1→3)-glucan with β(1→6)-branches. This is one of the most abundant carbon sources in the marine ecosystem. ...Laminarin has been found to possess various biological interesting properties, such as antioxidant and antimicrobial activities. An attractive feature of laminarin is its inherently low viscosity and high solubility in organic and aqueous solvents that facilitate processing. This makes laminarin an appealing material for the development of new hydrogels that can be easily injected through minimally invasive procedures or used for microfabrication of hydrogels. An approach for synthesizing photo-cross-linkable laminarin hydrogels is presented in this work for the first time. Photo-cross-linkable laminarin was prepared by chemical modification with acrylate groups. The synthesized photo-cross-linkable laminarin material provides the basis for the development of a new injectable system for biomedical purposes that could be used alone or with encapsulated cells or biological molecules. The cross-linking of the methacrylated laminarin is straightforward via photoinitiated polymerization. The possibility to control the methacrylation degree of laminarin and to prepare solutions up to at least 15% w/v permits us to obtain hydrogels with tuned and wide range of stiffness and swelling. Furthermore, the encapsulation of human-adipose-derived stem cells encapsulated in the photo-cross-linked hydrogels demonstrated in vitro biocompatibility.
In practical applications of optimization it is common to have several conflicting objective functions to optimize. Frequently, these functions are subject to noise or can be of black-box type, ...preventing the use of derivative-based techniques. We propose a novel multiobjective derivative-free methodology, calling it direct multisearch (DMS), which does not aggregate any of the objective functions. Our framework is inspired by the search/poll paradigm of direct-search methods of directional type and uses the concept of Pareto dominance to maintain a list of nondominated points (from which the new iterates or poll centers are chosen). The aim of our method is to generate as many points in the Pareto front as possible from the polling procedure itself, while keeping the whole framework general enough to accommodate other disseminating strategies, in particular, when using the (here also) optional search step. DMS generalizes to multiobjective optimization (MOO) all direct-search methods of directional type. We prove under the common assumptions used in direct search for single objective optimization that at least one limit point of the sequence of iterates generated by DMS lies in (a stationary form of) the Pareto front. However, extensive computational experience has shown that our methodology has an impressive capability of generating the whole Pareto front, even without using a search step. Two by-products of this paper are (i) the development of a collection of test problems for MOO and (ii) the extension of performance and data profiles to MOO, allowing a comparison of several solvers on a large set of test problems, in terms of their efficiency and robustness to determine Pareto fronts. PUBLICATION ABSTRACT
Biomedical applications of laminarin Zargarzadeh, Mehrzad; Amaral, Adérito J.R.; Custódio, Catarina A. ...
Carbohydrate polymers,
03/2020, Letnik:
232
Journal Article
Recenzirano
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•Review of key properties of laminarin.•Analysis of chemical modification strategies of this polysaccharide.•Discussion on its emerging applications in biomedicine.
The ocean is par ...excellence a fertile territory of biodiversity on our planet. Marine-derived polysaccharides have been applied as functional materials in biomedicine due to their attractive bioactive properties, safety, high availability and low-cost production. Laminarin (or laminaran), a low molecular weight β-glucan storage polysaccharide present in brown algae, can be (bio-) chemically modified to enhance its biological activity and employed in cancer therapies, drug/gene delivery, tissue engineering, antioxidant and anti-inflammatory functions. This review provides a brief overview on laminarin characteristics, modification strategies and highlights its pivotal biomedical applications.
Multiobjective optimization is a challenging scientific area, where the conflicting nature of the different objectives to be optimized changes the concept of problem solution, which is no longer a ...single point but a set of points, namely the Pareto front. In a posteriori preferences approach, when the decision maker is unable to rank objectives before the optimization, it is important to develop algorithms that generate approximations to the complete Pareto front of a multiobjective optimization problem, making clear the trade-offs between the different objectives. In this work, an algorithm based on a trust-region approach is proposed to approximate the set of Pareto critical points of a multiobjective optimization problem. Derivatives are assumed to be known, allowing the computation of Taylor models for the different objective function components, which will be minimized in two main steps: the extreme point step and the scalarization step. The goal of the extreme point step is to expand the approximation to the Pareto front, by moving towards the extreme points of it, corresponding to the individual minimization of each objective function component. The scalarization step attempts to reduce the gaps on the Pareto front, by solving adequate scalarization problems. The convergence of the method is analyzed and numerical experiments are reported, indicating the relevance of each feature included in the algorithmic structure and its competitiveness, by comparison against a state-of-art multiobjective optimization algorithm.
We present a derivative-free separable quadratic modeling and cubic regularization technique for solving smooth unconstrained minimization problems. The derivative-free approach is mainly concerned ...with building a quadratic model that could be generated by numerical interpolation or using a minimum Frobenius norm approach, when the number of points available does not allow to build a complete quadratic model. This model plays a key role to generate an approximated gradient vector and Hessian matrix of the objective function at every iteration. We add a specialized cubic regularization strategy to minimize the quadratic model at each iteration, that makes use of separability. We discuss convergence results, including worst case complexity, of the proposed schemes to first-order stationary points. Some preliminary numerical results are presented to illustrate the robustness of the specialized separable cubic algorithm.
The optimization of multimodal functions is a challenging task, in particular when derivatives are not available for use. Recently, in a directional direct search framework, a clever multistart ...strategy was proposed for global derivative-free optimization of single objective functions. The goal of the current work is to generalize this approach to the computation of global Pareto fronts for multiobjective multimodal derivative-free optimization problems. The proposed algorithm alternates between initializing new searches, using a multistart strategy, and exploring promising subregions, resorting to directional direct search. Components of the objective function are not aggregated and new points are accepted using the concept of Pareto dominance. The initialized searches are not all conducted until the end, merging when they start to be close to each other. The convergence of the method is analyzed under the common assumptions of directional direct search. Numerical experiments show its ability to generate approximations to the different Pareto fronts of a given problem.
Perinatal tissues are an abundant source of human extracellular matrix proteins, growth factors and stem cells with proved potential use in a wide range of therapeutic applications. Due to their ...placental origin, these tissues possess unique biological properties, including being angiogenic, anti-inflammatory, anti-fibrotic, anti-microbial and immune privileged. Additionally, as a temporary organ, placenta is usually discarded as a medical waste, thus providing an easily available, cost effective, ‘unlimited’ and ethical source of raw materials. Although some of these tissues, such as the amniotic membrane and umbilical cord, have been used in clinical practices, most of them continue to be highly under explored. This review aims to outline the most relevant applications of perinatal tissues as a source of biomaterials and stem cells in the exciting fields of tissue engineering and regenerative medicine (TERM), as well as highlight how these solutions can be used to overcome the shortage of adequate scaffolds and cell sources that currently hampers the translation of TERM strategies towards clinical settings.
Stem cells and extracellular matrix derived from perinatal tissues such as placenta and umbilical cord, have drawn great attention for use in a wide variety of applications in the biomedical field.
Due to their origin, these tissues possess unique biological properties, including being angiogenic, anti-inflammatory, anti-fibrotic, anti-microbial and immune privileged. Also they are typically considered medical waste, thus providing an easily available, cost effective, ‘unlimited’ and ethical source of raw materials.
This work aims to present and discuss the most relevant applications of perinatal tissues as a source of biomaterials and stem cells in the exciting fields of tissue engineering and regenerative medicine (TERM).
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To date, anticancer therapies with evidenced efficacy in preclinical models fail during clinical trials. The shortage of robust drug screening platforms that accurately predict patient's response ...underlie these misleading results. To provide a reliable platform for tumor drug discovery, we herein propose a relevant humanized 3D osteosarcoma (OS) model exploring the potential of methacryloyl platelet lysates (PLMA)-based hydrogels to sustain spheroid growth and invasion. The architecture and synergistic cell-microenvironment interaction of an invading tumor was recapitulated encapsulating spheroids in PLMA hydrogels, alone or co-cultured with osteoblasts and mesenchymal stem cells. The stem cells alignment toward OS spheroid suggested that tumor cells chemotactically attracted the surrounding stromal cells, which supported tumor growth and invasion into the hydrogels. The exposure of established models to doxorubicin revealed an improved drug resistance of PLMA-based models, comparing with scaffold-free spheroids. The proposed OS models highlighted the feasibility of PLMA hydrogels to support tumor invasion and recapitulate tumor-stromal cell crosstalk, demonstrating the potential of this 3D platform for complex tumor modelling.
Cell invasion mechanisms involved in tumor progression have been recapitulated in the field of 3D in vitro modeling, leveraging the great advance in biomimetic materials. In line with the growing interest in human-derived biomaterials, the aim of this study is to explore for the first time the potential of methacryloyl platelet lysates (PLMA)-based hydrogels to develop a humanized 3D osteosarcoma model to assess tumor invasiveness and drug sensitivity. By co-culturing tumor spheroids with human osteoblasts and human mesenchymal stem cells, this study demonstrated the importance of the synergistic tumor cell-microenvironment interaction in tumor growth, invasion and drug resistance. The established 3D osteosarcoma model highlighted the feasibility of PLMA hydrogels as a relevant 3D platform for complex tumor modelling.
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It is known that the Clarke generalized directional derivative is nonnegative along the limit directions generated by directional direct-search methods at a limit point of certain subsequences of ...unsuccessful iterates, if the function being minimized is Lipschitz continuous near the limit point. In this paper we generalize this result for discontinuous functions using Rockafellar generalized directional derivatives (upper subderivatives). We show that Rockafellar derivatives are also nonnegative along the limit directions of those subsequences of unsuccessful iterates when the function values converge to the function value at the limit point. This result is obtained assuming that the function is directionally Lipschitz with respect to the limit direction. It is also possible under appropriate conditions to establish more insightful results by showing that the sequence of points generated by these methods eventually approaches the limit point along the locally best branch or step function (when the number of steps is equal to two). The results of this paper are presented for constrained optimization and illustrated numerically.
The goal of this paper is to show that the use of minimum Frobenius norm quadratic models can improve the performance of direct-search methods. The approach taken here is to maintain the structure of ...directional direct-search methods, organized around a search and a poll step, and to use the set of previously evaluated points generated during a direct-search run to build the models. The minimization of the models within a trust region provides an enhanced search step. Our numerical results show that such a procedure can lead to a significant improvement of direct search for smooth, piecewise smooth, and noisy problems.
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