Characterization of a Delivery System Based on a Hyaluronic Acid 3D Scaffold and Gelatin Microparticles.

The objective of this study was to develop and characterize a novel hyaluronic acid (HA) 3D scaffold integrated with gelatin microparticles for sustained-delivery applications. To achieve this goal, the delivery microparticles were synthesized and thoroughly characterized, focusing on their crosslinking mechanisms (vanillin and genipin), degradation profiles, and release kinetics. Additionally, the cytotoxicity of the system was assessed, and its impact on the cell adhesion and distribution using mouse fibroblasts was examined.

Polylactic Acid Nanofiber Membranes Grafted with Carbon Nanotubes with Enhanced Mechanical and Electrical Properties.

Electroconductive materials based on poly(lactic acid) (PLA) electrospinning membranes grafted with carbon nanotubes (CNTs) functionalized with the carboxylic group R-COOH have been obtained. PLA electrospun membranes were modified with sulfuric acid (HSO) to oxidize its surface to subsequently graft the CNTs, the treatment time and drying of the membranes before grafting with CNTs being critical, influencing the final properties of the materials. SEM images showed that CNTs presented a uniform distribution on the surface of the PLA nanofibers, while FTIR spectra of PLA-CNTs materials revealed characteristic hydroxyl groups, as evidenced by absorption peaks of CNTs.

A Strategy for Magnetic and Electric Stimulation to Enhance Proliferation and Differentiation of NPCs Seeded over PLA Electrospun Membranes.

Neural progenitor cells (NPCs) have been shown to serve as an efficient therapeutic strategy in different cell therapy approaches, including spinal cord injury treatment. Despite the reported beneficial effects of NPC transplantation, the low survival and differentiation rates constrain important limitations. Herein, a new methodology has been developed to overcome both limitations by applying a combination of wireless electrical and magnetic stimulation to NPCs seeded on aligned poly(lactic acid) nanofibrous scaffolds for in vitro cell conditioning prior transplantation.

Electrical Stimulation Increases Axonal Growth from Dorsal Root Ganglia Co-Cultured with Schwann Cells in Highly Aligned PLA-PPy-Au Microfiber Substrates.

Nerve regeneration is a slow process that needs to be guided for distances greater than 5 mm. For this reason, different strategies are being studied to guide axonal growth and accelerate the axonal growth rate. In this study, we employ an electroconductive fibrillar substrate that is able to topographically guide axonal growth while accelerating the axonal growth rate when subjected to an exogenous electric field.

Development and evaluation of hyaluronan nanocomposite conduits for neural tissue regeneration.

Hyaluronan-based hydrogels are among the most promising neural tissue engineering materials because of their biocompatibility and the immunomodulation capabilities of their degradation byproducts. Despite these features, the problems related to their handling and mechanical properties have not yet been solved. In the present work it is proposed to address these drawbacks through the development of nanohybrid materials in which different nanometric phases (carbon nanotubes, mesoporous silica nanoparticles) are embedded in a crosslinked hyaluronan matrix.

BDNF-Gene Transfected Schwann Cell-Assisted Axonal Extension and Sprouting on New PLA-PPy Microfiber Substrates.

The work here reported analyzes the effect of increased efficiency of brain-derived neurotrophic factor (BDNF) production by electroporated Schwann cells (SCs) on the axonal extension in a coculture system on a biomaterial platform that can be of interest for the treatment of injuries of the nervous system, both central and peripheral. Rat SCs are electrotransfected with a plasmid coding for the BDNF protein in order to achieve an increased expression and release of this protein into the culture medium of the cells, performing the best balance between the level of transfection and the number of living cells. Gene-transfected SCs show an about 100-fold increase in the release of BDNF into the culture medium, compared to nonelectroporated SCs.

Axonal extension from dorsal root ganglia on fibrillar and highly aligned poly(lactic acid)-polypyrrole substrates obtained by two different techniques: Electrospun nanofibres and extruded microfibres.

The biological behaviour of Schwann cells (SCs) and dorsal root ganglia (DRG) on fibrillar, highly aligned and electroconductive substrates obtained by two different techniques is studied. Mats formed by nanometer-sized fibres of poly(lactic acid) (PLA) are obtained by the electrospinning technique, while bundles formed by micrometer-sized extruded PLA fibres are obtained by grouping microfibres together. Both types of substrates are coated with the electrically conductive polymer polypyrrole (PPy) and their morphological, physical and electrical characterization is carried out.

Conduits based on the combination of hyaluronic acid and silk fibroin: Characterization, in vitro studies and in vivo biocompatibility.

We address the production of structures intended as conduits made from natural biopolymers, capable of promoting the regeneration of axonal tracts. We combine hyaluronic acid (HA) and silk fibroin (SF) with the aim of improving mechanical and biological properties of HA. The results show that SF can be efficiently incorporated into the production process, obtaining conduits with tubular structure with a matrix of HA-SF blend.

Regenerative and Resorbable PLA/HA Hybrid Construct for Tendon/Ligament Tissue Engineering.

Tendon and ligament shows extremely limited endogenous regenerative capacity. Current treatments are based on the replacement and or augmentation of the injured tissue but the repaired tissue rarely achieve functionality equal to that of the preinjured tissue. To address this challenge, tissue engineering has emerged as a promising strategy.

Elastomeric cardiopatch scaffold for myocardial repair and ventricular support.

Objectives: Prevention of postischaemic ventricular dilatation progressing towards pathological remodelling is necessary to decrease ventricular wall deterioration. Myocardial tissue engineering may play a therapeutic role due to its capacity to replace the extracellular matrix, thereby creating niches for cell homing. In this experimental animal study, a biomimetic cardiopatch was created with elastomeric scaffolds and nanotechnologies.

Bridges of biomaterials promote nigrostriatal pathway regeneration.

Repair of central nervous system (CNS) lesions is difficulted by the lack of ability of central axons to regrow, and the blocking by the brain astrocytes to axonal entry. We hypothesized that by using bridges made of porous biomaterial and permissive olfactory ensheathing glia (OEG), we could provide a scaffold to permit restoration of white matter tracts. We implanted porous polycaprolactone (PCL) bridges between the substantia nigra and the striatum in rats, both with and without OEG.

Positioning of the cross-stitch on the modified Kessler core tendon suture.

Cryopreserved human tendons were sutured with different variations of a modified Kessler-type grasping suture in a series of different designs in order to assess the influence of the distance between the cross-stitch on the core suture (5 and 10 mm from the cut tendon edge) on the peripheral suture. An original mathematical model was employed to explain the mechanical behavior (strength, deformation, and distribution of load) of the different suture designs. The effect of the peripheral epitendinous suture, combined with the distance of the core suture, was evaluated.

Electrospun polycaprolactone/chitosan scaffolds for nerve tissue engineering: physicochemical characterization and Schwann cell biocompatibility.

Electrospun polycaprolactone (PCL)/chitosan (CH) blend scaffolds with different CH weight ratios were prepared to study the effect of scaffold composition on its physicochemical and biological properties. Scanning electron microscopy showed bead-free homogeneous randomly arranged nanofibers whose average diameter decreased from 240 to 110 nm with increasing CH content. The infrared spectra of the PCL/CH blends were very similar to the neat PCL scaffold.

Scaffolds based on hyaluronan and carbon nanotubes gels.

Physico-chemical and mechanical properties of hyaluronic acid/carbon nanotubes nanohybrids have been correlated with the proportion of inorganic nanophase and the preparation procedure. The mass fraction of -COOH functionalized carbon nanotubes was varied from 0 to 0.05.

Scaffolds of Hyaluronic Acid-Poly(Ethyl Acrylate) Interpenetrating Networks: Characterization and In Vitro Studies.

Hyaluronic acid (HA) provides many advantages to regenerative implants through its bioactive properties, but it also has many limitations as a biomaterial if it is not chemically modified. In order to overcome some of these limitations, HA has been combined with poly(ethyl acrylate) in the form of interpenetrating polymeric networks (IPNs), in which the HA network is crosslinked with divinyl sulfone. Scaffolds of this IPN have been produced through a template-leaching methodology, and their properties have been compared with those of single-network scaffolds made of either PEA or crosslinked HA.

Topologically controlled hyaluronan-based gel coatings of hydrophobic grid-like scaffolds to modulate drug delivery.

Scaffolds based on poly(ethyl acrylate) having interwoven channels were coated with a hyaluronan (HA) hydrogel to be used in tissue engineering applications. Controlled typologies of coatings evolving from isolated aggregates to continuous layers, which eventually clog the channels, were obtained by using hyaluronan solutions of different concentrations. The efficiency of the HA loading was determined using gravimetric and thermogravimetric methods, and the hydrogel loss during the subsequent crosslinking process was quantified, seeming to depend on the mass fraction of hyaluronan initially incorporated to the pores.

Hydrophilic surface modification of acrylate-based biomaterials.

Acrylic polymers have proved to be excellent with regard to cell adhesion, colonization and survival, in vitro and in vivo. Highly ordered and regular pore structures thereof can be produced with the help of polyamide templates, which are removed with nitric acid. This treatment converts a fraction of the ethyl acrylate side groups into acrylic acid, turning poly(ethyl acrylate) scaffolds into a more hydrophilic and pH-sensitive substrate, while its good biological performance remains intact.

Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity.

Unlabelled: Cell transplantation therapies in the nervous system are frequently hampered by glial scarring and cell drain from the damaged site, among others. To improve this situation, new biomaterials may be of help. Here, novel single-channel tubular conduits based on hyaluronic acid (HA) with and without poly-l-lactide acid fibers in their lumen were fabricated.

Neural tissue regeneration in experimental brain injury model with channeled scaffolds of acrylate copolymers.

The objective of the present study was to evaluate the biocompatibility and cell hosting ability of a copolymer scaffold based on ethyl acrylate (EA) and hydroxyl ethyl acrylate (HEA) in vivo after an experimental brain injury. Wistar rats were subjected to cryogenic traumatic brain injury. We evaluated the tissue response to the implanted materials after 8 weeks.

in vitro development of bioimplants made up of elastomeric scaffolds with peptide gel filling seeded with human subcutaneous adipose tissue-derived progenitor cells.

Myocardial tissue lacks the ability to regenerate itself significantly following a myocardial infarction. Thus, new strategies that could compensate this lack are of high interest. Cardiac tissue engineering (CTE) strategies are a relatively new approach that aims to compensate the tissue loss using combination of biomaterials, cells and bioactive molecules.

Bioactive organic-inorganic poly(CLMA-co-HEA)/silica nanocomposites.

A series of novel poly(CLMA-co-HEA)/silica nanocomposites is synthesized from caprolactone 2-(methacryloyloxy)ethyl ester (CLMA) and 2-hydroxyethyl acrylate (HEA) as organic comonomers and the simultaneous sol-gel polymerization of tetraethyloxysilane (TEOS) as silica precursor, in different mass ratios up to a 30 wt% of silica. The nanocomposites are characterized as to their mechanical and thermal properties, water sorption, bioactivity and biocompatibility, reflecting the effect on the organic matrix provided by the silica network formation. The nanocomposites nucleate the growth of hydroxyapatite (HAp) on their surfaces when immersed in the simulated body fluid of the composition used in this work.

New semi-biodegradable materials from semi-interpenetrated networks of poly(ϵ-caprolactone) and poly(ethyl acrylate).

Semi-degradable materials may have many applications. Here poly(ethyl acrylate) and poly(ϵ-caprolactone) were combined as semi-interpenetrated networks, and thoroughly characterized in terms of final composition, interactions between components, wettability, and mechanical properties. PCL modulates the mechanical properties of the PEA elastomeric network.

Design and assembly procedures for large-sized biohybrid scaffolds as patches for myocardial infarct.

Objective: To assemble a biohybrid cardiac patch consisting of a large (5 × 5 cm) elastomer scaffold whose pores are filled with a self-assembling peptide (SAP) gel entrapping adipose stem cells, to be used as a novel implant in a big animal model (sheep) of myocardial infarction. The study focuses on the way to determine optimal procedures for incorporating the SAP solution and the cells in the patch to ensure cell colonization and a homogeneous cell distribution in the construct before implantation. The problems associated with the scale-up of the different procedures raised by the large size of the construct are discussed.

Hyaluronic acid-silica nanohybrid gels.

Excessive water sorption and low mechanical properties are a severe drawback in some biomedical applications of hyaluronic acid (HA). A way to improve these properties is here explored through the novel concept of nanohybrid hydrogels consisting of a HA matrix including different amounts of silica-derived species. This inorganic filler phase controls the mechanical and swelling properties of HA cross-linked matrices.

Grid polymeric scaffolds with polypeptide gel filling as patches for infarcted tissue regeneration.

Scaffolds of poly(ethyl acrylate) (PEA) with interconnected cylindrical orthogonal pores filled with a self-assembling peptide (SAP) gel are here proposed as patches for infarcted tissue regeneration. These combined systems aim to support cell therapy and meet further requirements posed by the application: the three-dimensional architecture of the elastomeric scaffold is expected to lodge the cells of interest in the damaged zone avoiding their death or migration, and at the same time conduct cell behavior and give mechanical support if necessary; the ECM-like polypeptide gel provides a cell-friendly aqueous microenvironment, facilitates diffusion of nutrients and cell wastes and is expected to improve the distribution and viability of the seeded cells within the pores and stimulate angiogenesis.