Cell Biocompatibility Research Articles

Evaluation of in vitro biocompatibility of human pulp stem cells with allogeneic, alloplastic, and xenogeneic grafts under the influence of extracellular vesicles

Therapies using dental pulp stem cells (DPSCs) or stem cell-derived extracellular vesicles (EVs) have shown promising applications for bone tissue engineering. This in vitro experiment evaluated the joint osteogenic capability of DPSCs and EVs on alloplastic (maxresorp), allogeneic (maxgraft), and xenogeneic (cerabone) bone grafts. We hypothesize that osteogenic differentiation and the proliferation of human DPSCs vary between bone grafts and are favorable under the influence of EVs. DPSCs were obtained from human wisdom teeth, and EVs derived from DPSCs were isolated from cell culture medium. DPSCs were seeded on alloplastic, allogeneic, and xenogeneic bone graft substitutes for control, and the same scaffolds were administered with EVs in further groups. The cellular uptake of EVs into DPSC cells was assessed by confocal laser scanning microscopy. Cell vitality staining and calcein acetoxymethyl ester staining were used to evaluate cell attachment and proliferation. Cell morphology was determined using scanning electron microscopy, and osteogenic differentiation was explored by alkaline phosphatase and Alizarin red staining. Within the limitations of an in vitro study without pathologies, the results suggest that especially the use of xenogeneic bone graft substitutes with DPSCS and EVs may represent a promising treatment approach for alveolar bone defects.

Biomimetic hydrogel derived from decellularized dermal matrix facilitates skin wounds healing.

Cutaneous wound healing affecting millions of people worldwide represents an unsolvable clinical issue that is frequently challenged by scar formation with dramatical pain, impaired mobility and disfigurement. Herein, we prepared a kind of light-sensitive decellularized dermal extracellular matrix-derived hydrogel with fast gelling performance, biomimetic porous microstructure and abundant bioactive functions. On account of its excellent cell biocompatibility, this ECM-derived hydrogel could induce a marked cellular infiltration and enhance the tube formation of HUVECs. In vivo experiments based upon excisional wound splinting model showed that the hydrogel prominently imparted skin wound healing, as evidenced by notably increased skin appendages and well-organized collagen expression, coupled with significantly enhanced angiogenesis. Moreover, the skin regeneration mediated by this bioactive hydrogel was promoted by an accelerated M1-to-M2 macrophage phenotype transition. Consequently, the decellularized dermal matrix-derived bioactive hydrogel orchestrates the entire skin healing microenvironment to promote wound healing and will be of high value in treatment of cutaneous wound healing. As such, this biomimetic ddECMMA hydrogel provides a promising versatile opinion for the clinical translation.

Improved Biocompatibility and Angiogenesis of the Bone Titanium Scaffold through ERK1/2 Signaling Mediated by an Attached Strontium Element.

The promotion of early osseointegration is crucial for the success of biomedical titanium implants. Physical and chemical modifications to the material surface can significantly compensate for the lack of biocompatibility and early osseointegration of the implant. In this study, we implanted strontium onto titanium plates and analyzed the effect of strontium-doped materials on angiogenesis and biocompatibility in the human bone structure. Our findings demonstrated that strontium-loaded titanium sheet materials effectively promote human umbilical vein endothelial cell (HUVEC) biocompatibility and vascular differentiation ability, as evidenced by proliferation-apoptosis assays, RT-qPCR for vascular neogenesis markers, ELISA for vascular endothelial growth factor (VEGF) levels, and nitric oxide (NO) analysis. Mechanism studies based on RNAseq and Western blotting analysis revealed that strontium can promote titanium material biocompatibility with HUVEC cells and vascular neovascularization ability by activating the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Meanwhile, blocking the ERK1/2 signaling pathway could reverse the promotional effect of vascular formation. Overall, we have successfully fabricated a multifunctional biocompatible bone implant with better histocompatibility and angiogenesis compared to uncoated implants.

Recent advance in bioactive hydrogels for repairing spinal cord injury: material design, biofunctional regulation, and applications.

Functional hydrogels show potential application in repairing spinal cord injury (SCI) due to their unique chemical, physical, and biological properties and functions. In this comprehensive review, we present recent advance in the material design, functional regulation, and SCI repair applications of bioactive hydrogels. Different from previously released reviews on hydrogels and three-dimensional scaffolds for the SCI repair, this work focuses on the strategies for material design and biologically functional regulation of hydrogels, specifically aiming to show how these significant efforts can promoting the repairing performance of SCI. We demonstrate various methods and techniques for the fabrication of bioactive hydrogels with the biological components such as DNA, proteins, peptides, biomass polysaccharides, and biopolymers to obtain unique biological properties of hydrogels, including the cell biocompatibility, self-healing, anti-bacterial activity, injectability, bio-adhesion, bio-degradation, and other multi-functions for repairing SCI. The functional regulation of bioactive hydrogels with drugs/growth factors, polymers, nanoparticles, one-dimensional materials, and two-dimensional materials for highly effective treating SCI are introduced and discussed in detail. This work shows new viewpoints and ideas on the design and synthesis of bioactive hydrogels with the state-of-the-art knowledges of materials science and nanotechnology, and will bridge the connection of materials science and biomedicine, and further inspire clinical potential of bioactive hydrogels in biomedical fields.

An Injectable, Shape-Retaining Collagen Hydrogel Cross-linked Using Thiol-Maleimide Click Chemistry for Sealing Corneal Perforations.

Injectable hydrogels show great promise in developing novel regenerative medicine solutions and present advantages for minimally invasive applications. Hydrogels based on extracellular matrix components, such as collagen, have the benefits of cell adhesiveness, biocompatibility, and degradability by enzymes. However, to date, reported collagen hydrogels possess severe shortcomings, such as nonbiocompatible cross-linking chemistry, significant swelling, limited range of mechanical properties, or gelation kinetics unsuitable for in vivo injection. To solve these issues, we report the design and characterization of an injectable collagen hydrogel based on covalently modified acetyl thiol collagen cross-linked using thiol-maleimide click chemistry. The hydrogel is injectable for up to 72 h after preparation, shows no noticeable swelling, is transparent, can be molded in situ, and retains its shape in solution for at least one year. Notably, the hydrogel mechanical properties can be fine-tuned by simply adjusting the reactant stoichiometries, which to date was only reported for synthetic polymer hydrogels. The biocompatibility of the hydrogel is demonstrated in vitro using human corneal epithelial cells, which maintain viability and proliferation on the hydrogels for at least seven days. Furthermore, the developed hydrogel showed an adhesion strength on soft tissues similar to fibrin glue. Additionally, the developed hydrogel can be used as a sealant for repairing corneal perforations and can potentially alleviate the off-label use of cyanoacrylate tissue adhesive for repairing corneal perforations. Taken together, these characteristics show the potential of the thiol collagen hydrogel for future use as a prefabricated implant, injectable filler, or as sealant for corneal repair and regeneration.

The Cell Biocompatibility of a new Polycaprolactone-based Endodontics Sealer Compared with AH Plus Sealer

Background:One of the important materials needed for root treatment is the sealers. They fill the space between the gutta and the canal walls and create a suitable seal to prevent the colonization of oral microorganisms in the peri-apical tissues and inside the canal space.Aim:The aim of this study was to prepare and test the cell biocompatibility of a new polycaprolactone-based endodontics sealer in comparison to AH plus sealer against dental pulp stem cells.Methods:MTT assay was used to evaluate the cytotoxicity.Results:The results showed that AH plus showed moderate cytotoxicity effects against cells (the number of living cells was 49.45 ± 10.56%). However, for the new sealer, the number of living cells was ≥ 80% (81% ± 4.11). Thus, the sample was non-cytotoxic against tested cells.Conclusion:More investigations are needed on the new sealer to validate its biocompatibility and usefulness.

Microstructure and mechanical properties of biodegradable Zn-2Cu-0.1Ti alloy for orthopedic applications

Bioresorbable implants are intended to be biocompatible, mechanically stable, and to corrode gradually in response to an appropriate host response. In this work, a Zn-2Cu-0.1Ti (ZCT) alloy was fabricated by a combination of casting and hot-rolling. X-ray diffraction analysis revealed the presence of both TiZn16 phase and a CuZn4 phase in the alloy. ZCT showed an extraordinary increase in yield strength compared with the unalloyed Zn to 248 MPa (from 100 MPa) and a similar elongation to failure (33–34%). The alloy also possesses a relatively low corrosion rate when immersed in simulated body fluid. The 50 % extract of ZCT alloy exhibits excellent biocompatibility for MC3T3-E1 cells. These results indicate that the ZCT alloy has potential for clinical applications.

An ultrafast water absorption composite cryogel containing Iron-doped bioactive glass with rapid hemostatic ability for non-compressible and coagulopathic bleeding

Traditional hemostatic materials have limited hemostatic effect on non-compressible wound, that is likely to develop into coagulopathy and leads to high mortality. As a powerful hemostatic material, in addition to having the function of forming solid physical barriers and effectively activating coagulation factors to rapidly control hemostasis, it should also has the ability to bypass the coagulation pathway to handle the bleeding of coagulopathic patients. In this work, we designed a QCOC composite cryogel by gelation of quaternized chitosan (QCS) and hydroxyethyl cellulose oxide (OHEC) at low temperature. Meanwhile, iron-doped bioactive glass (FeBG) as an active substance was introduced into the QCOC composite cryogel to promote erythrocyte aggregation by ion dissolution and activate intrinsic and extrinsic pathways. QCOC/FeBG composite cryogel had interconnected macroporous structure, ultrafast water absorption performance (reaching water absorption saturation in 4 s) and good shape memory properties (restoring to its original shape in 1 s). Additionally, the composite cryogel showed excellent antibacterial properties against S. aureus and E. coli as well as good cell biocompatibility. Furthermore, the QCOC/FeBG composite cryogel showed excellent hemostatic performance in the model of liver non-compressible hemorrhage with coagulation disorders, and the hemostasis time and blood loss were 60.87 ± 2.09 s and 366.38 ± 32.69 mg respectively, which were much lower than commercial gelatin sponge (196.62 ± 19.02 s and 1439.37 ± 165.27 mg). These results proved that QCOC/FeBG composite cryogel has excellent hemostatic properties, antibacterial properties, portability and usability, indicating a great potential as a timely hemostatic material in daily civil and military hemostasis.

22 nm Resolution Achieved by Femtosecond Laser Two-Photon Polymerization of a Hyaluronic Acid Vinyl Ester Hydrogel.

Three-dimensional (3D) bioinspired hydrogels have played an important role in tissue engineering, owing to their advantage of excellent biocompatibility. Here, the two-photon polymerization (TPP) of a 3D hydrogel with high precision has been investigated, using the precursor with hyaluronic acid vinyl ester (HAVE) as the biocompatibility hydrogel monomer, 3,3'-((((1E,1'E)-(2-oxocyclopentane-1,3-diylidene) bis(methanylylidene)) bis(4,1-phenylene)) bis(methylazanediyl))dipropanoate as the water-soluble initiator, and dl-dithiothreitol (DTT) as the click-chemistry cross-linker. The TPP properties of the HAVE precursors have been comprehensively investigated by adjusting the solubility and the formulation of the photoresist. The feature line width of 22 nm has been obtained at a processing laser threshold of 3.67 mW, and the 3D hydrogel scaffold structures have been fabricated. Furthermore, the average value of Young's modulus is 94 kPa for the 3D hydrogel, and cell biocompatibility has been demonstrated. This study would provide high potential for achieving a 3D hydrogel scaffold with highly precise configuration in tissue engineering and biomedicine.

Zn-MOF hydrogel: regulation of ROS-mediated inflammatory microenvironment for treatment of atopic dermatitis

Atopic dermatitis (AD) is a chronic and recurrent inflammation disease associated with immune dysfunction. The high level of reactive oxygen species (ROS) causes high oxidative stress and further results in the deterioration of AD. At the same time, the ROS produced by bacterial infection can further aggravate AD. Here, the prepared PVA-based hydrogel (Gel) has a high ROS scavenging ability, and the antibacterial agent Zn-MOF(ZIF-8) loaded into the hydrogel shows a lasting and effective antibacterial activity. Thus, a Zn-MOF hydrogel (Gel@ZIF-8) is prepared to regulate ROS-mediated inflammatory microenvironment. In vitro experiments show that Gel@ZIF-8 has good antibacterial effect and cell biocompatibility. In the AD-induced mouse model, Gel@ZIF-8 can significantly enhance the therapeutic effect, such as reduce the thickness of epidermis, the number of mast cells and IgE antibodies. The results indicate that the ROS-scavenging hydrogel could treat the AD by regulating the inflammatory microenvironment, providing a promising treatment for managing AD.

Liver-targeting MRI contrast agent based on galactose functionalized o-carboxymethyl chitosan.

Commercial gadolinium (Gd)-based contrast agents (GBCAs) play important role in clinical diagnostic of hepatocellular carcinoma, but their diagnostic efficacy remained improved. As small molecules, the imaging contrast and window of GBCAs is limited by low liver targeting and retention. Herein, we developed a liver-targeting gadolinium (Ⅲ) chelated macromolecular MRI contrast agent based on galactose functionalized o-carboxymethyl chitosan, namely, CS-Ga-(Gd-DTPA)n, to improve hepatocyte uptake and liver retention. Compared to Gd-DTPA and non-specific macromolecular agent CS-(Gd-DTPA)n, CS-Ga-(Gd-DTPA)n showed higher hepatocyte uptake, excellent cell and blood biocompatibility in vitro. Furthermore, CS-Ga-(Gd-DTPA)n also exhibited higher relaxivity in vitro, prolonged retention and better T1-weighted signal enhancement in liver. At 10days post-injection of CS-Ga-(Gd-DTPA)n at a dose of 0.03mMGd/Kg, Gd had a little accumulation in liver with no liver function damage. The good performance of CS-Ga-(Gd-DTPA)n gives great confidence in developing liver-specifc MRI contrast agents for clinical translation.

Fibrous polypeptide based bioscaffold delivery of minocycline hydrochloride for nerve regeneration

Neural tissue engineering is a technology with the potential to treat irreversible neurodegenerative diseases. We chose poly (γ-benzyl-l-glutamate) (PBG) and its hydrolyzed copolymer (poly (γ-benzyl-glutamate)80-r-(γ –glutamic acid)20) (PBGA) as the raw materials to make fibrous scaffolds by electrospinning process. These raw materials are biocompatible polypeptides which contain the neurotransmitter glutamate. Morphologically, the scaffolds consist of aligned fibers, which is important for directionality. Minocycline hydrochloride (MH) is a neuroprotective antibiotic obviously shown to enhance neurite growth, but is unstable in phosphate buffer solution. By incorporating and immobilizing MH into either PBG or PBGA polypeptide scaffolds, we created a stable drug delivery system. After 7-day release, the cumulative release of MH from PBGA scaffold was 42.65%. Nerve growth factor (NGF) responsive rat pheochromocytoma (PC12) cells were cultured on the scaffold to assess cell biocompatibility and proliferation. We found cell viability and differentiation improved when cultured on scaffolds bearing 2 wt% and 4 wt% of MH. PC12 cells cultured on PBGA incorporating 4 wt% MH exhibited the longest neurite outgrowth of 190.29 μm, the average is 33% increase over that of pristine PBGA after 5-days of NGF mediated differentiation. These polypeptide-based scaffolds loaded with MH are a promising drug delivery system for neural tissue engineering.

Lignin-facilitated growth of Ag/CuNPs on surface-activated polyacryloamidoxime nanofibers for superior antibacterial activity with improved biocompatibility

IntroductionNanofibers are one of the role-playing innovations of nanotechnology. Their high surface-to-volume ratio allows them to be actively functionalized with a wide range of materials for a variety of applications. The functionalization of nanofibers with different metal nanoparticles (NPs) has been studied widely to fabricate antibacterial substrates to battle antibiotic-resistant bacteria. However, metal NPs show cytotoxicity to living cells, thereby restricting their application in biomedicine. ObjectivesTo minimize the cytotoxicity of NPs, biomacromolecule lignin was employed as both a reducing and capping agent to green synthesize silver (Ag) and copper (Cu) NPs on the surface of highly activated polyacryloamidoxime nanofibers. The activation of polyacrylonitrile (PAN) nanofibers via amidoximation was employed for enhanced loading of NPs to achieve superior antibacterial activity. MethodologyAt first, electrospun PAN nanofibers (PANNM) were activated to produce polyacryloamidoxime nanofibers (AO-PANNM) by immersing PANNM in a solution of Hydroxylamine hydrochloride (HH) and Na2CO3 under controlled conditions. Later, Ag and Cu ions were loaded by immersing AO-PANNM in different molar concentrations of AgNO3 and CuSO4 solutions in a stepwise manner. The reduction of Ag and Cu ions into NPs to fabricate bimetal-coated PANNM (BM-PANNM) was carried out via alkali lignin at 37 °C for 3 h in a shaking incubator with ultrasonication every 1 h. ResultsAO-APNNM and BM-PANNM hold their nano-morphology except for some changes in fiber orientation. XRD analysis demonstrated the formation of Ag and CuNPs as evident from their respective spectral band. Maximum 8.46 ± 0.14 wt% and 0.98 ± 0.04 wt% Ag and Cu species were loaded on AO-PANNM, respectively as revealed by ICP spectrometric analysis. The hydrophobic PANNM turned into super hydrophilic, having WCA of 14 ± 3.32° after amidoximation which further reduced to 0° for BM-PANNM. However, the swelling ratio of PANNM reduced from 13.19 ± 0.18 g/g to 3.72 ± 0.20 g/g for AO-PANNM. Even at the third cycle test against S. aureus strains, 0.1Ag/Cu-PANNM, 0.3Ag/Cu-PANNM, and 0.5Ag/Cu-PANNM displayed bacterial reduction of 71.3 ± 1.64 %, 75.2 ± 1.91 %, and 77.24 ± 1.25 %, respectively. On 3rd cycle test against E. coli, above 82 % bacterial reduction was noticed for all BM-PANNM. Amidoximation increased COS-7 cell viability up to 82 %. The cell viability of 0.1Ag/Cu-PANNM, 0.3Ag/Cu-PANNM, and 0.5Ag/Cu-PANNM was found to be ∼68 %, ∼62, and 54 %, respectively. In LDH assay, almost no release of LDH was detected, suggesting the compatibility of the cell membrane in contact with BM-PANNM. The improved biocompatibility of BM-PANNM even at higher loading (%) of NPs must be ascribed to the controlled release of metal species in the early stage, antioxidant, and biocompatible lignin capping of NPs. ConclusionsBM-PANNM displayed superior antibacterial activity against E. coli and S. aureus bacterial strains and acceptable biocompatibility of COS-7 cells even at higher loading (%) of Ag/CuNPs. Our findings suggest that BM-PANNM can be used as a potential antibacterial wound dressing and other antibacterial applications where sustained antibacterial activity is needed.

Development and Characterization of a AuNP-Genipin-Viscoelastic Collagen Material.

Lower back pain is one of the leading causes of disability, affecting 11.9% of the population worldwide and studies have shown that intervertebral disc degeneration is a common cause for chronic lower back pain. We have explored the combination of three components, viscoelastic collagen, genipin, and gold nanoparticles to determine its potential to promote regeneration of the intervertebral disc, specifically for nucleus pulposus regeneration. The goal of this study was to develop, fabricate and characterize different formulations of viscoelastic collagen conjugated with gold nanoparticles and genipin to assess the feasibility as a tissue template. Results demonstrated the successful attachment of gold nanoparticles to the viscoelastic collagen utilizing the genipin crosslinker. For each of the viscoelastic collagen compositions examined, cell biocompatibility was achieved. The results also demonstrated an increase in stiffness of the material with different sizes and concentrations of AuNPs. Results from the TEM and STEM also demonstrated that the viscoelastic collagen that was developed did not display the characteristic D banding pattern of polymerized collagen. The findings from this study could lead to the development of a more efficient and cost-effective treatment for patients with chronic back pain caused by IVD degeneration.

Long-lived room-temperature phosphorescent complex of B, N, P co-doped carbon dots and silica for afterglow imaging

Room temperature phosphorescent (RTP) materials based on carbon dots (CDs) have attracted abundant attention in bioimaging owing to their long lifetimes and wide Stokes shift, which can reduce the autofluorescence and light scattering in tissue. Although solid-state RTP CDs have been widely reported at present, long-lived RTP CDs in aqueous solutions still remain a challenge because they are usually quenched by oxygen in water. This work develops a heteroatom doping strategy to synthesize long-lived matrix-free phosphorescent B, N, P co-doped CDs (B, N, P-CDs) with cross-linked structure and rich hydrogen bonding network. B, N, P-CDs have an ultralong phosphorescence lifetime of 1.89 s. Subsequently, the complex of B, N, P co-doped CDs and silica (B, N, P-CDs@SiO2) was further obtained by coating the surfaces of B, N, P-CDs with silica by sol-gel method to further confine their molecular vibrations and rotations, which shows an excellent RTP property in aqueous solution with a phosphorescent lifetime of 1.97 s. In addition, the complex displays good biocompatibility, low cytotoxicity, and ability of phosphorescent labeling cells and organism. All these results extend a potential application of the B, N, P-CDs@SiO2 complex as phosphorescent bioimaging probe.

A photothermal therapy enhanced mechano-bactericidal hybrid nanostructured surface

Polymeric materials that have been extensively applied in medical devices, wearable electronics, and food packaging are readily contaminated by bothersome pathogenic bacteria. Bioinspired mechano-bactericidal surfaces can deliver lethal rupture for contacted bacterial cells through mechanical stress. However, the mechano-bactericidal activity based only on polymeric nanostructures is not satisfactory, especially for the Gram-positive strain which is generally more resistant to mechanical lysis. Here, we show that the mechanical bactericidal performance of polymeric nanopillars can be significantly enhanced by the combination of photothermal therapy. We fabricated the nanopillars through the combination of low-cost anodized aluminum oxide (AAO) template-assisted method with an environment-friendly Layer-by-Layer (LbL) assembly technique of tannic acid (TA) and iron ion (Fe3+). The fabricated hybrid nanopillar exhibited remarkable bactericidal performances (more than 99%) toward both Gram-negative Pseudomonas aeruginosa (P. aeruginosa) and stubborn Gram-positive Staphylococcus aureus (S. aureus) bacteria. Notably, this hybrid nanostructured surface displayed excellent biocompatibility for murine L929 fibroblast cells, indicating a selective biocidal activity between bacterial cells and mammalian cells. Thus, the concept and antibacterial system described here present a low-cost, scalable, and highly repeatable strategy for the construction of physical bactericidal nanopillars on polymeric films with high performance and biosafety, but without any risks of causing antibacterial resistance.

Resorbable membrane design: In vitro characterization of silver doped-hydroxyapatite-reinforced XG/PEI semi-IPN composite

In this study, the production and characterization of silver-doped hydroxyapatite (AgHA) reinforced Xanthan gum (XG) and Polyethyleneimine (PEI) reinforced semi-interpenetrating polymer network (IPN) biocomposite, known to be used as bone cover material for therapeutic purposes in bone tissue, were performed. XG/PEI IPN films containing 2AgHA nanoparticles were produced by simultaneous condensation and ionic gelation. Characteristics of 2AgHA-XG/PEI nanocomposite film were evaluated by structural, morphological (SEM, XRD, FT-IR, TGA, TM, and Raman) and biological activity analysis (degradation, MTT, genotoxicity, and antimicrobial activity) techniques. In the physicochemical characterization, it was determined that 2AgHA nanoparticles were homogeneously dispersed in the XG/PEI-IPN membrane at high concentration and the thermal and mechanical stability of the formed film were high. The nanocomposites showed high antibacterial activity against Acinetobacter Baumannii (A.Baumannii), Staphylococcus aureus (S.aureus), and Streptococcus mutans (S.mutans). L929 exhibited good biocompatibility for fibroblast cells and was determined to support the formation of MCC cells. It was shown that a resorbable 2AgHA-XG/PEI composite material was obtained with a high degradation rate and 64% loss of mass at the end of the 7th day. Physico-chemically developed biocompatible and biodegradable XG-2AgHA/PEI nanocomposite semi-IPN films possessed an important potential for the treatment of defects in bone tissue as an easily applicable bone cover. Besides, it was noted that 2AgHA-XG/PEI biocomposite could increase cell viability, especially in dental-bone treatments for coating, filling, and occlusion.

Microstructure enhanced biocompatibility in laser additively manufactured CoCrMo biomedical alloy

The present work investigated biocompatibility of the unique nanostructural surface morphology inherently evolved in laser-based additively manufactured CoCrMo after biocorrosion in simulated body fluid at physiological temperature (37 °C). The extremely rapid thermokinetics intrinsically associated with the laser-based additive manufacturing technique resulted in heterogeneous cellular dendritic solidification morphologies with selective elemental segregation along the cell boundaries within CoCrMo samples. Consequently, a selective and spatially varying electrochemical response resulted in generation of a nanoscale surface morphology (crests and troughs) due to differential localized electrochemical etching. Also, depth of the trough regions was a function of the applied potential difference during potentiodynamic polarization which resulted in samples with varying morphological ratio (depth of trough/width of cell wall). CoCrMo with such nanoscale surface undulations were proposed for enhanced biocompatibility in terms of viability, spreading, and integration of MT3C3 pre-osteoblasts cells elucidated via MTT assay, immunofluorescence, and microscopy techniques. Furthermore, the influence of the morphological ratio, characteristic to the additively deposited CoCrMo after electrochemical etching (biocorrosion) on biocompatibility of MT3C3 pre-osteoblasts cells was qualitatively and quantitatively compared to a mirror-polished flat CoCrMo surface.

Pulsed electrodeposition of MXenes/HAp multiple biological functional coatings on 3D printed porous Ti-6Al-4V bone tissue engineering scaffold

Titanium and its alloys have been widely used as bone tissue engineering scaffold due to their excellent biocompatibility and mechanical strength. In order to promote bone ingrowth, integration and match the mechanical properties of natural bone tissue, this study proposed diamond-like microstructure porous Ti-6Al-4V scaffolds for personalized bone defect repair. In order to prepare the multiple biological functional coatings on the curve surface inside of the 3D printed porous scaffolds, pulsed electrodeposition method was proposed to obtain multiple layers of Ti3C2Tx/HAp composited coatings. Delaminated Ti3C2Tx has an ultra-thin microstructure according to transmission electron microscopy (TEM) observation and is well dispersed in electrolyte. X-ray diffraction (XRD) characterization shows that Ti3C2Tx has been synthesized and regulates more CaHPO4‧2H2O (DCPD) to Hydroxyapatite (HAP) conversion, which is confirmed by Fourier transform infrared spectroscopy (FTIR) at 0.2 mg/mL concentration. Scanning electron microscopy (SEM) shows that the morphologies of composite coatings are closely related to Ti3C2Tx content due to the availability of effective voltages for electrodeposition. By means of finite element method, deposition thickness and distribution of coatings were simulated to explore the precipitation kinetics and selection of electrodeposition parameters and a current density of 15 mA/cm2 was ultimately used. In vitro electrochemical corrosion of Ti3C2Tx/HAp coatings were tested in human simulated body fluid (SBF) to verify its corrosion resistance in physiological environment and Ti3C2Tx/HAp composited coatings possess the best corrosion resistance according to linear scanning voltammetry (LSV) and electrochemical impedance spectroscopy (EIS) tests. In vitro MC3T3-E1 cell culturing studies were investigated to evaluate cell behaviors and biocompatibility of these coatings. The results indicate that cells grow well on the surface of composite coatings without showing cytotoxicity and cell morphologies show a good spreading state and a trend of inward growth.

Alginate-Gelatin Self-Healing Hydrogel Produced via Static-Dynamic Crosslinking.

Alginate-gelatin hydrogels mimicking extracellular matrix (ECM) of soft tissues have been generated by static-dynamic double crosslinking, allowing fine control over the physical and chemical properties. Dynamic crosslinking provides self-healing and injectability attributes to the hydrogel and promotes cell migration and proliferation, while the static network improves stability. The static crosslinking was performed by enzymatic coupling of the tyrosine residues of gelatin with tyramine residues inserted in the alginate backbone, catalyzed by horseradish peroxidase (HRP). The dynamic crosslinking was obtained by functionalizing alginate with 3-aminophenylboronic acid which generates a reversible bond with the vicinal hydroxyl groups of the alginate chains. Varying the ratio of alginate and gelatin, hydrogels with different properties were obtained, and the most suitable for 3D soft tissue model development with a 2.5:1 alginate:gelatin molar ratio was selected. The selected hydrogel was characterized with a swelling test, rheology test, self-healing test and by cytotoxicity, and the formulation resulted in transparent, reproducible, varying biomaterial batch, with a fast gelation time and cell biocompatibility. It is able to modulate the loss of the inner structure stability for a longer time with respect to the formulation made with only covalent enzymatic crosslinking, and shows self-healing properties.