Primary MSCs for Personalized Medicine: Ethical Challenges, Isolation and Biocompatibility Evaluation of 3D Electrospun and Printed Scaffolds.

Autologous cell therapy uses patients' own cells to deliver precise and ideal treatment through a personalized medicine approach. Isolation of patients' cells from residual tissue extracted during surgery involves specific planning and lab steps. In the present manuscript, a path from isolation to in vitro research with human mesenchymal stem cells (MSCs) obtained from residual bone tissues is described as performed by a medical unit in collaboration with a research center. Ethical issues have been addressed by formulating appropriate harvesting protocols according to European regulations. Samples were collected from 19 patients; 10 of them were viable and after processing resulted in MSCs. MSCs were further differentiated in osteoblasts to investigate the biocompatibility of several 3D scaffolds produced by electrospinning and 3D printing technologies; traditional orthopedic titanium and nanostructured titanium substrates were also tested. 3D printed scaffolds proved superior compared to other substrates, enabling significantly improved response in osteoblast cells, indicating that their biomimetic structure and properties make them suitable for synthetic tissue engineering. The present research is a proof of concept that describes the process of primary stem cells isolation for in vitro research and opens avenues for the development of personalized cell platforms in the case of patients with orthopedic trauma. The demonstration model has promising perspectives in personalized medicine practices.

Toughening and Healing of CFRPs by Diels-Alder-Based Nano-Modified Resin through Melt Electro-Writing Process Technique.

In the current study, a novel approach in terms of the incorporation of self-healing agent (SHA) into unidirectional (UD) carbon fiber reinforced plastics (CFRPs) has been demonstrated. More precisely, Diels-Alder (DA) mechanism-based resin (Bis-maleimide type) containing or not four layered graphene nanoplatelets (GNPs) at the amount of 1 wt% was integrated locally in the mid-thickness area of CFRPs by melt electro-writing process (MEP). Based on that, CFRPs containing or not SHA were fabricated and further tested under Mode I interlaminar fracture toughness experiments. According to experimental results, modified CFRPs exhibited a considerable enhancement in the interlaminar fracture toughness properties (peak load (Pmax) and fracture toughness energy I (GIC) values). After Mode I interlaminar fracture toughness testing, the damaged samples followed the healing process and then were tested again under identical experimental conditions. The repeating of the tests revealed moderate healing efficiency (H.E.) since part of the interlaminar fracture toughness properties were restored. Furthermore, three-point bending (3PB) experiments were conducted, with the aim of assessing the effect of the incorporated SHA on the in-plane mechanical properties of the final CFRPs. Finally, optical microscopy (OM) examinations were performed to investigate the activated/involved damage mechanisms.

Fabrication and Characterization of Polylactic Acid Electrospun Scaffolds Modified with Multi-Walled Carbon Nanotubes and Hydroxyapatite Nanoparticles.

The solution electrospinning process (SEP) is a cost-effective technique in which a wide range of polymeric materials can be electrospun. Electrospun materials can also be easily modified during the solution preparation process (prior SEP). Based on this, the aim of the current work is the fabrication and nanomodification of scaffolds using SEP, and the investigation of their porosity and physical and mechanical properties. In this study, polylactic acid (PLA) was selected for scaffold fabrication, and further modified with multi-walled carbon nanotubes (MWCNTs) and hydroxyapatite (HAP) nanoparticles. After fabrication, porosity calculation and physical and mechanical characterization for all scaffold types were conducted. More precisely, the morphology of the fibers (in terms of fiber diameter), the surface properties (in terms of contact angle) and the mechanical properties under the tensile mode of the fabricated scaffolds have been investigated and further compared against pristine PLA scaffolds (without nanofillers). Finally, the scaffold with the optimal properties was proposed as the candidate material for potential future cell culturing.

Fabrication and Characterization of Polyetherimide Electrospun Scaffolds Modified with Graphene Nano-Platelets and Hydroxyapatite Nano-Particles.

Solution electrospinning process (SEP) is a versatile technique for generating non-woven fibrous materials intended to a wide range of applications. One of them is the production of fibrous and porous scaffolds aiming to mimic bone tissue, as artificial extracellular matrices (ECM). In the present work, pure and nano-modified electrospun polyetherimide (PEI) scaffolds have been successfully fabricated. The nano-modified ones include (a) graphene nano-platelets (GNPs), (b) hydroxyapatite (HAP), and (c) mixture of both. After fabrication, the morphological characteristics of these scaffolds were revealed by using scanning electron (SEM) and transmission electron (TEM) microscopies, while porosity and mean fiber diameter were also calculated. In parallel, contact angle experiments were conducted so that the hydrophilicity level of these materials to be determined. Finally, the mechanical performance of the fabricated scaffolds was investigated by conducting uniaxial tensile tests. Ιn future work, the fabricated scaffolds will be further utilized for investigation as potential candidate materials for cell culture with perspective in orthopedic applications.

Graphene Nanoplatelet- and Hydroxyapatite-Doped Supramolecular Electrospun Fibers as Potential Materials for Tissue Engineering and Cell Culture.

Porous and fibrous artificial extracellular matrices (ECM) called scaffolds are considered to be promising avenues of research in the field of biomedical engineering, including tissue fabrication through cell culture. The current work deals with the fabrication of new matrix-type scaffolds through electrospinning, in order to support future three-dimensional tissue formation. The selected material for the fabrication of these scaffolds was a supramolecular polymer (SP) that is based on ureiodypyrimidone hydrogen bonding units (UPy). More precisely, pure SP and modified electrospun scaffolds with (a) graphene nanoplatelets (GNPs), (b) hydroxyapatite (HA), and (c) a mixture of both were fabricated for the needs of the current study. The aim of this work is to engineer and to characterize SP electrospun scaffolds (with and without fillers) and study whether the introduction of the fillers improve the physical and mechanical properties of them. The obtained results indicate that doping the SP scaffolds with GNPs led to improved apparent mechanical properties while HA seems to slightly deteriorate them. For all cases, doping provided thinner fibers with a more hydrophilic surface. Taking together, these types of SP scaffolds can be further studied as potential candidate for cell culture.

3-Arm star pyrene-functional PMMAs for efficient exfoliation of graphite in chloroform: fabrication of graphene-reinforced fibrous veils.

3-Arm PMMAs end-functionalized by pyrene were designed as dispersing/stabilizing agents for the liquid-phase exfoliation of graphite in low-boiling point solvents like chloroform. The synthetic procedure comprised ARGET ATRP controlled polymerization, click chemistry and the quaternization reaction of triazole, ensuring tailor-made, well-defined pyrene-functional star PMMAs. Among a series of different pyrene-functional macromolecular topologies, the (PMMA-py2)3 proved the most efficient exfoliation agent giving relatively high graphene concentration (0.36 mg ml-1) at exceptionally low polymer/graphite mass ratio (mP/mGF = 0.003) and short sonication time (3 h). A 5-cycle iterative procedure relying on the redispersion of the sediment was developed yielding CG = 1.29 mg ml-1 with 14.8% exfoliation yield, under the favorable conditions of 10.5 h total shear mixing/tip sonication time and overall mP/mGF ratio as low as 0.15. In parallel, all-atom molecular dynamics simulations were conducted which helped understand the mechanism by which pyrene-functional macromolecular topologies act as efficient dispersing agents of graphene. Finally the G@(PMMA-Py)3 hybrids were well dispersed into the PMMA matrix by electrospinning to fabricate graphene-based nanocomposite fibrous veils. These graphene/polymer nanocomposites exhibited enhanced stiffness and strength by a factor of 4.4 with 1.5 wt% graphene hybrids as nanofillers.