Magnetically Actuated Cell-Robot System: Precise Control, Manipulation, and Multimode Conversion.

Border-nearing microrobots with self-propelling and navigating capabilities have promising applications in micromanipulation and bioengineering, because they can stimulate the surrounding fluid flow for object transportation. However, ensuring the biosafety of microrobots is a concurrent challenge in bioengineering applications. Here, macrophage template-based microrobots (cell robots) that can be controlled individually or in chain-like swarms are proposed, which can transport various objects. The cell robots are constructed using the phagocytic ability of macrophages to load nanomagnetic particles while maintaining their viability. The robots exhibit high position control accuracy and generate a flow field that can be used to transport microspheres and sperm when exposed to an external magnetic field near a wall. The cell robots can also form chain-like swarms to transport a large object (more than 100 times the volume). This new insight into the manipulation of macrophage-based cell robots provides a new concept by converting other biological cells into microrobots for micromanipulation in biomedical applications.

PGS/HAp Microporous Composite Scaffold Obtained in the TIPS-TCL-SL Method: An Innovation for Bone Tissue Engineering.

In this research, we synthesize and characterize poly(glycerol sebacate) pre-polymer (pPGS) (1H NMR, FTiR, GPC, and TGA). Nano-hydroxyapatite (HAp) is synthesized using the wet precipitation method. Next, the materials are used to prepare a PGS-based composite with a 25 wt.% addition of HAp. Microporous composites are formed by means of thermally induced phase separation (TIPS) followed by thermal cross-linking (TCL) and salt leaching (SL). The manufactured microporous materials (PGS and PGS/HAp) are then subjected to imaging by means of SEM and µCT for the porous structure characterization. DSC, TGA, and water contact angle measurements are used for further evaluation of the materials. To assess the cytocompatibility and biological potential of PGS-based composites, preosteoblasts and differentiated hFOB 1.19 osteoblasts are employed as in vitro models. Apart from the cytocompatibility, the scaffolds supported cell adhesion and were readily populated by the hFOB1.19 preosteoblasts. HAp-facilitated scaffolds displayed osteoconductive properties, supporting the terminal differentiation of osteoblasts as indicated by the production of alkaline phosphatase, osteocalcin and osteopontin. Notably, the PGS/HAp scaffolds induced the production of significant amounts of osteoclastogenic cytokines: IL-1ß, IL-6 and TNF-α, which induced scaffold remodeling and promoted the reconstruction of bone tissue. Initial biocompatibility tests showed no signs of adverse effects of PGS-based scaffolds toward adult BALB/c mice.

Functional medium entropy alloys for joint replacement: An atomistic perspective of material deformation and a correlation to wear, corrosion, and biocompatibility.

The present study adopts a multi-facet approach to design bio inspired concentrated alloys for potential application as articulating surfaces in joint replacements. A series of equiatomic, Nb rich and Ti rich TiMoNbZr based medium entropy alloys (MEAs) were processed via arc melting and their mechanical, in-vitro corrosion, wear, and in vitro and in vivo biocompatibility were investigated. Equiatomic MEA had primarily bcc with minor hcp phases where the single bcc was achieved with the addition of Nb. The single bcc Nb rich alloy resulted in 13 % elongation, much higher than equiatomic or Ti rich alloy. All the MEAs showed comparatively higher yield strength due to the climb of edge dislocations which is the main rate limiting mechanism at 300 K, as evident molecular dynamics (MD) simulation. The locally fluctuating energy landscape promotes kinks on edge dislocation, and at local minima nanoscale segments gets pinned. Upon yielding the entangled kink leaves a trail of vacancies/interstitials and escapes via climb motion to render high yield strength. The higher corrosion and pitting resistance of Nb enriched alloys can be attributed to the stable ZrO2, Nb2O5, TiO2, and MoO3 oxides, high polarization resistance (106-105 Ωcm-2), and low defect densities (1016-1018). In vitro cell-materials interaction using MC3T3-E1 showed bioinert but cytocompatible nature of the MEAs. The wear rate of the MEAs was in the range of 7-9 × 10-5 mm3N-1m-1. The wear debris did not show any tissue necrosis when implanted in rabbit femur rather new bone regeneration can be seen around the particles. STATEMENT OF SIGNIFICANCE: In the present work, a noble Nb enriched MEAs with superior mechanical, in vitro wear, corrosion and cytocompatibility properties was designed for articulating surfaces in joint replacement.

Visible-Light-Responsive Novel Ru(II)-Metallo-Antibiotics with Potential Antibiofilm and Antibacterial Activity.

Growing challenges with antibiotic resistance pose immense challenges in combating microbial infections and biofilm prevention on medical devices. Lately, antibacterial photodynamic therapy (aPDT) is now emerging as an alternative therapy to overcome this problem. Herein, we synthesized and characterized four Ru(II)-complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF6 (Ru1), [Ru(ph-tpy)(dpq)Cl]PF6 (Ru2), [Ru(ph-tpy)(dppz)Cl]PF6 (Ru3), and [Ru(ph-tpy)(dppn)Cl]PF6 (Ru4) (where 4'-phenyl-2,2':6',2″-terpyridine = ph-tpy; 2,2'-bipyridine = bpy; dipyrido[3,2-f:2',3'-h]quinoxaline = dpq; dipyrido[3,2-a:2',3'-c]phenazine = dppz; and Benzo[I]dipyrido[3,2-a:2',3'-c]phenazine = dppn), among which Ru2-Ru4 are novel. Octahedral geometry of the complexes with a RuN5Cl core was evident from the crystal structure of Ru2. Ru1-Ru4 showed an MLCT absorption band in the 450-600 nm region, useful for aPDT performances. Further, optimum triplet excited state energy and excellent photostability of Ru1-Ru4 made them good photosensitizers for aPDT. Ru1-Ru4 demonstrated enhanced antimicrobial activity on visible-light exposure (400-700 nm, 10 J cm-2), confirmed using different antibacterial assays. Mechanistic studies revealed that inhibition of bacterial growth was due to the generation of oxidative stress (via NADH oxidation and ROS generation) upon treatment with Ru2-Ru4, resulting in destruction of the bacterial wall. Ru2 performed best killing performance against both Gram-negative (Escherichia coli) and Gram-positive (Bacillus subtilis) bacteria when exposed to light. Ru2-Ru4, when coated on a polydimethylsiloxane (PDMS) disk, showed long-term reusability and durable antibiofilm properties. Molecular docking confirmed the efficient interaction of Ru2-Ru4 with FabH (regulates fatty acid biosynthesis of E. coli) and PgaB (gives structural stability and helps biofilm formation of E. coli), resulting in probable downregulation. In vivo studies with healthy Wistar rats confirmed the biocompatibility of Ru2. This study shows that these lead complexes (Ru2-Ru4) can be used as potent alternative antimicrobial agents in low concentrations toward bacterial eradication with photodynamic therapy (PDT).

Hyaluronic acid-based hydrogel coatings on Ti6Al4V implantable biomaterial with multifunctional antibacterial activity.

Today, the treatment of implant-associated infections with conventional mono-functional antibacterial coatings has not been effective enough for a prosperous long-term implantation. Therefore, biomedical industry is making considerable efforts on the development of novel antibacterial coatings with a combination of more than one antibacterial strategies that interact synergistically to reinforce each other. Therefore, in this work hyaluronic acid-based (HA) hydrogel coatings were created on the surface Ti6Al4V biomaterial with 1,4-butanediol diglycidyl ether (Ti-HABDDE) and divinyl sulfone (Ti-HADVS) crosslinking agents. Hydrogel coatings displayed an extraordinary in vivo biocompatibility, a remarkable ability to promote cell proliferation, differentiation and mineralization, and capability to sustainedly release drugs. Finally, HA-based hydrogel coatings demonstrated an outstanding multifunctional antibacterial activity: bacteria-repelling (51-55 % of S. aureus and 27-40 % of E. coli), bacteria-killing (82-119 % of S. aureus and 83-87 % of E. coli) and bactericide release killing (drug-loaded hydrogel coatings, R > 2).

High-Performance Implantable Sensors based on Anisotropic Magnetoresistive La0.67Sr0.33MnO3 for Biomedical Applications.

We present the design, fabrication, and characterization of an implantable neural interface based on anisotropic magnetoresistive (AMR) magnetic-field sensors that combine reduced size and high performance at body temperature. The sensors are based on La0.67Sr0.33MnO3 (LSMO) as a ferromagnetic material, whose epitaxial growth has been suitably engineered to get uniaxial anisotropy and large AMR output together with low noise even at low frequencies. The performance of LSMO sensors of different film thickness and at different temperatures close to 37 °C has to be explored to find an optimum sensitivity of ∼400%/T (with typical detectivity values of 2 nT·Hz-1/2 at a frequency of 1 Hz and 0.3 nT·Hz-1/2 at 1 kHz), fitted for the detection of low magnetic signals coming from neural activity. Biocompatibility tests of devices consisting of submillimeter-size LSMO sensors coated by a thin poly(dimethyl siloxane) polymeric layer, both in vitro and in vivo, support their high suitability as implantable detectors of low-frequency biological magnetic signals emerging from heterogeneous electrically active tissues.

In Vivo Chronic Brain Cortex Signal Recording Based on a Soft Conductive Hydrogel Biointerface.

In neuroscience, the acquisition of neural signals from the brain cortex is crucial to analyze brain processes, detect neurological disorders, and offer therapeutic brain-computer interfaces. The design of neural interfaces conformable to the brain tissue is one of today's major challenges since the insufficient biocompatibility of those systems provokes a fibrotic encapsulation response, leading to an inaccurate signal recording and tissue damage precluding long-term/permanent implants. The design and production of a novel soft neural biointerface made of polyacrylamide hydrogels loaded with plasmonic silver nanocubes are reported herein. Hydrogels are surrounded by a silicon-based template as a supporting element for guaranteeing an intimate neural-hydrogel contact while making possible stable recordings from specific sites in the brain cortex. The nanostructured hydrogels show superior electroconductivity while mimicking the mechanical characteristics of the brain tissue. Furthermore, in vitro biological tests performed by culturing neural progenitor cells demonstrate the biocompatibility of hydrogels along with neuronal differentiation. In vivo chronic neuroinflammation tests on a mouse model show no adverse immune response toward the nanostructured hydrogel-based neural interface. Additionally, electrocorticography acquisitions indicate that the proposed platform permits long-term efficient recordings of neural signals, revealing the suitability of the system as a chronic neural biointerface.

Multifunctional antibacterial chitosan-based hydrogel coatings on Ti6Al4V biomaterial for biomedical implant applications.

Among biomedical community, great efforts have been realized to develop antibacterial coatings that avoid implant-associated infections. To date, conventional mono-functional antibacterial strategies have not been effective enough for successful long-term implantations. Consequently, researchers have recently focused their attention on novel bifunctional or multifunctional antibacterial coatings, in which two or more antibacterial mechanisms interact synergistically. Thus, in this work different chitosan-based (CHI) hydrogel coatings were created on Ti6Al4V surface using genipin (Ti-CHIGP) and polyethylene glycol (Ti-CHIPEG) crosslinking agents. Hydrogel coatings demonstrated an exceptional in vivo biocompatibility plus a remarkable ability to promote cell proliferation and differentiation. Lastly, hydrogel coatings demonstrated an outstanding bacteria-repelling (17-28 % of S. aureus and 33-43 % of E. coli repelled) and contact killing (186-222 % of S. aureus and 72-83 % of E. coli damaged) ability. Such bifunctional antibacterial activity could be further improved by the controlled release of drugs resulting in powerful multifunctional antibacterial coatings.

In Vitro and In Vivo Biocompatible and Controlled Resveratrol Release Performances of HEMA/Alginate and HEMA/Gelatin IPN Hydrogel Scaffolds.

Scaffold hydrogel biomaterials designed to have advantageous biofunctional properties, which can be applied for controlled bioactive agent release, represent an important concept in biomedical tissue engineering. Our goal was to create scaffolding materials that mimic living tissue for biomedical utilization. In this study, two novel series of interpenetrating hydrogel networks (IPNs) based on 2-hydroxyethyl methacrylate/gelatin and 2-hydroxyethyl methacrylate/alginate were crosslinked using N-ethyl-N'-(3-dimethyl aminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Characterization included examining the effects of crosslinker type and concentration on structure, morphological and mechanical properties, in vitro swelling, hydrophilicity as well as on the in vitro cell viability (fibroblast cells) and in vivo (Caenorhabditis elegans) interactions of novel biomaterials. The engineered IPN hydrogel scaffolds show an interconnected pore morphology and porosity range of 62.36 to 85.20%, favorable in vitro swelling capacity, full hydrophilicity, and Young's modulus values in the range of 1.40 to 7.50 MPa. In vitro assay on healthy human fibroblast (MRC5 cells) by MTT test and in vivo (Caenorhabditis elegans) survival assays show the advantageous biocompatible properties of novel IPN hydrogel scaffolds. Furthermore, in vitro controlled release study of the therapeutic agent resveratrol showed that these novel scaffolding systems are suitable controlled release platforms. The results revealed that the use of EDC and the combination of EDC/NHS crosslinkers can be applied to prepare and tune the properties of the IPN 2-hydroxyethyl methacrylate/alginate and 2-hydroxyethyl methacrylate/gelatin hydrogel scaffolds series, which have shown great potential for biomedical engineering applications.

In vivo time-course biocompatibility assessment of biomagnetic nanoparticles-based biomaterials for tissue engineering applications.

Novel artificial tissues with potential usefulness in local-based therapies have been generated by tissue engineering using magnetic-responsive nanoparticles (MNPs). In this study, we performed a comprehensive in vivo characterization of bioengineered magnetic fibrin-agarose tissue-like biomaterials. First, in vitro analyses were performed and the cytocompatibility of MNPs was demonstrated. Then, bioartificial tissues were generated and subcutaneously implanted in Wistar rats and their biodistribution, biocompatibility and functionality were analysed at the morphological, histological, haematological and biochemical levels as compared to injected MNPs. Magnetic Resonance Image (MRI), histology and magnetometry confirmed the presence of MNPs restricted to the grafting area after 12 weeks. Histologically, we found a local initial inflammatory response that decreased with time. Structural, ultrastructural, haematological and biochemical analyses of vital organs showed absence of damage or failure. This study demonstrated that the novel magnetic tissue-like biomaterials with improved biomechanical properties fulfil the biosafety and biocompatibility requirements for future clinical use and support the use of these biomaterials as an alternative delivery route for magnetic nanoparticles.