Biodegradable Microparticles for Regenerative Medicine: A State of the Art and Trends to Clinical Application

peer reviewedTissue engineering and cell therapy are very attractive in terms of potential applications but remain quite challenging regarding the clinical aspects. Amongst the different strategies proposed to facilitate their implementation in clinical practices, biodegradable microparticles have shown promising outcomes with several advantages and potentialities. This critical review aims to establish a survey of the most relevant materials and processing techniques to prepare these micro vehicles. Special attention will be paid to their main potential applications, considering the regulatory constraints and the relative easiness to implement their production at an industrial level to better evaluate their application in clinical practices

Mechanochemical Transformations of Polysaccharides: A Systematic Review

Taking into consideration the items of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this study reviews application of mechanochemical approaches to the modification of polysaccharides. The ability to avoid toxic solvents, initiators, or catalysts during processes is an important characteristic of the considered approach and is in line with current trends in the world. The mechanisms of chemical transformations in solid reactive systems during mechanical activation, the structure and physicochemical properties of the obtained products, their ability to dissolve and swell in different media, to form films and fibers, to self-organize in solution and stabilize nanodispersed inorganic particles and biologically active substances are considered using a number of polysaccharides and their derivatives as examples

Polysaccharides as Stabilizers for Polymeric Microcarriers Fabrication.

Biodegradable polymeric microparticles are widely used in drug delivery systems with prolonged-release profiles and/or cell microcarriers. Their fabrication via the oil/water emulsion solvent evaporation technique has normally required emulsifiers in the aqueous phase. The present work aims to evaluate the effectiveness of various polysaccharides, such as chitosan, hyaluronic acid, cellulose, arabinogalactan, guar and their derivatives, as an alternative to synthetic surfactants for polylactide microparticle stabilization during their fabrication. Targeted modification of the biopolymer's chemical structure was also tested as a tool to enhance polysaccharides' emulsifying ability. The transformation of biomacromolecules into a form of nanoparticle via bottom-up or top-down methods and their subsequent application for microparticle fabrication via the Pickering emulsion solvent evaporation technique was useful as a one-step approach towards the preparation of core/shell microparticles. The effect of polysaccharides' chemical structure and the form of their application on the polylactide microparticles' total yield, size distribution and morphology was evaluated. The application of polysaccharides has great potential in terms of the development of green chemistry and the biocompatibility of the formed microparticles, which is especially important in biomedicine application

Hydrophobic Modification of Chitosan via Reactive Solvent-Free Extrusion

Hydrophobic derivatives of polysaccharides possess an amphiphilic behavior and are widely used as rheological modifiers, selective sorbents, and stabilizers for compositions intended for various applications. In this work, we studied the mechanochemical reactions of chitosan alkylation when interacting with docosylglycidyl and hexadecylglycidyl ethers in the absence of solvents at shear deformation in a pilot twin-screw extruder. The chemical structure and physical properties of the obtained derivatives were characterized by elemental analysis, FT-IR spectroscopy, dynamic light scattering, scanning electron microscopy, and mechanical tests. According to calculations for products soluble in aqueous media, it was possible to introduce about 5–12 hydrophobic fragments per chitosan macromolecule with a degree of polymerization of 500–2000. The length of the carbon chain of the alkyl substituent significantly affects its reactivity under the chosen conditions of mechanochemical synthesis. It was shown that modification disturbs the packing ability of the macromolecules, resulting in an increase of plasticity and drop in the elastic modulus of the film made from the hydrophobically modified chitosan samples

Macroporous Hyaluronic Acid/Chitosan Polyelectrolyte Complex-Based Hydrogels Loaded with Hydroxyapatite Nanoparticles: Preparation, Characterization and In Vitro Evaluation

The aim of the study was to fabricate and characterize composite macroporous hydrogels based on a hyaluronic acid/chitosan (Hyal/Ch) polyelectrolyte complex (PEC) loaded with homogeneously distributed hydroxyapatite nanoparticles (nHAp), and to evaluate them in vitro using mouse fibroblasts (L929), osteoblast-like cells (HOS) and human mesenchymal stromal cells (hMSC). Hydrogel morphology as a function of the hydroxyapatite nanoparticle content was studied using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The mean pore size in the Hyal/Ch hydrogel was 204 ± 25 μm. The entrapment of nHAp (1 and 5 wt. %) into the Hyal/Ch hydrogel led to a mean pore size decrease (94 ± 2 and 77 ± 9 μm, relatively). Swelling ratio and weight loss of the hydrogels in various aqueous media were found to increase with an enhancement of a medium ionic strength. Cell morphology and localization within the hydrogels was studied by CLSM. Cell viability depended upon the nHAp content and was evaluated by MTT-assay after 7 days of cultivation in the hydrogels. An increase of the hydroxyapatite nanoparticles loading in a range of 1–10 wt. % resulted in an enhancement of cell growth and proliferation for all hydrogels. Maximum cell viability was obtained in case of the Hyal/Ch/nHAp-10 sample (10 wt. % nHAp), while a minimal cell number was found for the Hyal/Ch/nHAp-1 hydrogel (1 wt. % nHAp). Thus, the proposed simple original technique and the design of PEC hydrogels could be promising for tissue engineering, in particular for bone tissue repair

Controlled Structure of Polyester/Hydroxyapatite Microparticles Fabricated via Pickering Emulsion Approach

Biodegradable polyester/hydroxyapatite microparticles are widely proposed as microcarriers for drug/cell delivery or scaffolds for bone tissue regeneration. The current research implements the surfactant-free approach for the fabrication of polyester-based microparticles filled with hydroxyapatite nanoparticles (nHA) via the oil/water Pickering emulsion solvent evaporation technique for the first time, to the best of our knowledge. The process of polyester microparticle fabrication using nHA for the oil/water interface stabilization was studied as a function of phase used for nHA addition, which allows the preparation of a range of microparticles either filled with nHA or having it as a shell over the polymeric core. The effect of processing conditions (polymer nature, polymer/nHA ratio, ultrasound treatment) on particles’ total yield, size distribution, surface and volume morphology, and chemical structure was analyzed using SEM, EDX, Raman spectroscopy, and mapping. Addition of nHA either within the aqueous or oil phase allowed the effective stabilization of the oil/water interface without additional molecular surfactants, giving rise to hybrid microparticles in which total yield, size distribution, and surface morphology depended on all studied processing conditions. Preliminary ultrasound treatment of any phase before the emulsification process led to a complex effect but did not affect the homogeneity of nHA distribution within the polymeric core of the hybrid microparticles

A Novel Approach to Design Chitosan-Polyester Materials for Biomedical Applications

A novel approach to design chitosan-polyester materials is reported. The method is based on mechanical activation and effective intermixing of the substrates under high pressure and shear deformation in the course of solid-state reactive blending. The marked departure of this approach from previous practice resides on exploitation of a variety of chemical transformations of the solid polymers that become feasible under conditions of plastic flow. Low temperatures (above Tg but below the melting points of the crystalline polymers) are maintained throughout the process, minimizing mechanical and oxidative degradation of the polymers. Morphology as well as structural, mechanical, and relaxation properties of those prepared blends of chitosan with semicrystalline poly(L,L-lactide) and amorphous poly(D,L-lactide-co-glycolide) has been studied. Grafting of polyester moieties onto chitosan chains was found to occur under employed pressures and shear stresses. The prepared polymer blends have demonstrated an amphiphilic behavior with a propensity to disperse in organic solvents that widens possibilities to transform them into promising materials for various biomedical applications

Plasma Treatment of Poly(ethylene terephthalate) Films and Chitosan Deposition: DC- vs. AC-Discharge

Plasma treatment is one of the most promising tools to control surface properties of materials tailored for biomedical application. Among a variety of processing conditions, such as the nature of the working gas and time of treatment, discharge type is rarely studied, because it is mainly fixed by equipment used. This study aimed to investigate the effect of discharge type (direct vs. alternated current) using air as the working gas on plasma treatment of poly(ethylene terephthalate) films, in terms of their surface chemical structure, morphology and properties using X-ray photoelectron spectroscopy, scanning electron microscopy, atomic force microscopy and contact angle measurements. The effect of the observed changes in terms of subsequent chitosan immobilization on plasma-treated films was also evaluated. The ability of native, plasma-treated and chitosan-coated films to support adhesion and growth of mesenchymal stem cells was studied to determine the practicability of this approach for the biomedical application of poly(ethylene terephthalate) films

Electrospinning vs. Electro-Assisted Solution Blow Spinning for Fabrication of Fibrous Scaffolds for Tissue Engineering

Biodegradable polymeric fibrous non-woven materials are widely used type of scaffolds for tissue engineering. Their morphology and properties could be controlled by composition and fabrication technology. This work is aimed at development of fibrous scaffolds from a multicomponent polymeric system containing biodegradable synthetic (polylactide, polycaprolactone) and natural (gelatin, chitosan) components using different methods of non-woven mats fabrication: electrospinning and electro-assisted solution blow spinning. The effect of the fabrication technique of the fibrous materials onto their morphology and properties, including the ability to support adhesion and growth of cells, was evaluated. The mats fabricated using electrospinning technology consist of randomly oriented monofilament fibers, while application of solution blow spinning gave a rise to chaotically arranged multifilament fibers. Cytocompatibility of all fabricated fibrous mats was confirmed using in vitro analysis of metabolic activity, proliferative capacity and morphology of NIH 3T3 cell line. Live/Dead assay revealed the formation of the highest number of cell–cell contacts in the case of multifilament sample formed by electro-assisted solution blow spinning technology