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Herein, we present poly(butylene 1,4-cyclohexanedicarboxylate) (PBCE) films characterized by an unpatterned microstructure and a specific hydrophobicity, capable of boosting a drastic cytoskeleton architecture remodeling, culminating with the neuronal-like differentiation of human bone marrow-mesenchymal stem cells (hBM-MSCs). We have used two different filming procedures to prepare the films, solvent casting (PBCE) and compression-moulding (PBCE*). PBCE film had a rough and porous surface with spherulite-like aggregations (Ø = 10-20 µm) and was characterized by a water contact angle = 100°. PBCE* showed a smooth and continuous surface without voids and visible spherulite-like aggregations and was more hydrophobic (WCA = 110°). Both surface characteristics were modulated through the copolymerization of different amounts of ether-oxygen-containing co-units into PBCE chemical structure. We showed that only the surface characteristics of PBCE-solvent-casted films steered hBM-MSCs toward a neuronal-like differentiation. hBM-MSCs lost their canonical mesenchymal morphology, acquired a neuronal polarized shape with a long cell protrusion (≥150 µm), expressed neuron-specific class III ß-tubulin and microtubule-associated protein 2 neuronal markers, while nestin, a marker of uncommitted stem cells, was drastically silenced. These events were observed as early as 2-days after cell seeding. Of note, the phenomenon was totally absent on PBCE* film, as hBM-MSCs maintained the mesenchymal shape and behavior and did not express neuronal/glial markers.

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Three-dimensional (3D) bioprinting is an appealing and revolutionary manufacturing approach for the accurate placement of biologics, such as living cells and extracellular matrix (ECM) components, in the form of a 3D hierarchical structure to fabricate synthetic multicellular tissues. Many synthetic and natural polymers are applied as cell printing bioinks. One of them, alginate (Alg), is an inexpensive biomaterial that is among the most examined hydrogel materials intended for vascular, cartilage, and bone tissue printing. It has also been studied pertaining to the liver, kidney, and skin, due to its excellent cell response and flexible gelation preparation through divalent ions including calcium. Nevertheless, Alg hydrogels possess certain negative aspects, including weak mechanical characteristics, poor printability, poor structural stability, and poor cell attachment, which may restrict its usage along with the 3D printing approach to prepare artificial tissue. In this review paper, we prepare the accessible materials to be able to encourage and boost new Alg-based bioink formulations with superior characteristics for upcoming purposes in drug delivery systems. Moreover, the major outcomes are discussed, and the outstanding concerns regarding this area and the scope for upcoming examination are outlined.

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Therapeutic advancements in the treatment of various ocular diseases is often linked to the development of efficient drug delivery systems (DDSs), which would allow a sustained release while maintaining therapeutic drug levels in the target tissues. In this way, ocular tissue/cell response can be properly modulated and designed in order to produce a therapeutic effect. An ideal ocular DDS should encapsulate and release the appropriate drug concentration to the target tissue (therapeutic but non-toxic level) while preserving drug functionality. Furthermore, a constant release is usually preferred, keeping the initial burst to a minimum. Different materials are used, modified, and combined in order to achieve a sustained drug release in both the anterior and posterior segments of the eye. After giving a picture of the different strategies adopted for ocular drug release, this review article provides an overview of the biomaterials that are used as drug carriers in the eye, including micro- and nanospheres, liposomes, hydrogels, and multi-material implants; the advantages and limitations of these DDSs are discussed in reference to the major ocular applications.

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Corneal transplantation remains the ultimate treatment option for advanced stromal and endothelial disorders. Corneal tissue engineering has gained increasing interest in recent years, as it can bypass many complications of conventional corneal transplantation. The human cornea is an ideal organ for tissue engineering, as it is avascular and immune-privileged. Mimicking the complex mechanical properties, the surface curvature, and stromal cytoarchitecure of the in vivo corneal tissue remains a great challenge for tissue engineering approaches. For this reason, automated biofabrication strategies, such as bioprinting, may offer additional spatial control during the manufacturing process to generate full-thickness cell-laden 3D corneal constructs. In this review, we discuss recent advances in bioprinting and biomaterials used for in vitro and ex vivo corneal tissue engineering, corneal cell-biomaterial interactions after bioprinting, and future directions of corneal bioprinting aiming at engineering a full-thickness human cornea in the lab.

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In the tissue engineering research field, nanobiomaterials highlight the impact of novel bioactive materials in both current applications and their potentials in future progress for tissue engineering and regenerative medicine. Tissue engineering is a well-investigated and challenging biomedical field, with promising perspectives to improve and support quality of life for the patient. To assess the response of those extracellular matrices (ECMs), induced by biomedical materials, this review will focus on cell response to natural biomaterials for biocompatibility.

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Regenerative therapies including stem cell treatments hold promise to allow curing patients affected by severe cardiac muscle diseases. However, the clinical efficacy of stem cell therapy remains elusive, so far. The two key roadblocks that still need to be overcome are the poor cell engraftment into the injured myocardium and the limited knowledge of the ideal mixture of bioactive factors to be locally delivered for restoring heart function. Thus, therapeutic strategies for cardiac repair are directed to increase the retention and functional integration of transplanted cells in the damaged myocardium or to enhance the endogenous repair mechanisms through cell-free therapies. In this context, biomaterial-based technologies and tissue engineering approaches have the potential to dramatically impact cardiac translational medicine. This review intends to offer some consideration on the cell-based and cell-free cardiac therapies, their limitations and the possible future developments.

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The cross-talk between stem cells and their microenvironment has been shown to have a direct impact on stem cells' decisions about proliferation, growth, migration, and differentiation. It is well known that stem cells, tissues, organs, and whole organisms change their internal architecture and composition in response to external physical stimuli, thanks to cells' ability to sense mechanical signals and elicit selected biological functions. Likewise, stem cells play an active role in governing the composition and the architecture of their microenvironment. Is now being documented that, thanks to this dynamic relationship, stemness identity and stem cell functions are maintained. In this work, we review the current knowledge in mechanobiology on stem cells. We start with the description of theoretical basis of mechanobiology, continue with the effects of mechanical cues on stem cells, development, pathology, and regenerative medicine, and emphasize the contribution in the field of the development of ex-vivo mechanobiology modelling and computational tools, which allow for evaluating the role of forces on stem cell biology.

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Study of cell-biomaterial interaction is a crucial aspect of bone tissue engineering to find a state-of-the-art functional substitute. In present study, the Wharton's jelly mesenchymal stem cells (hWJ-MSCs) behavior on three-dimensional biomimetic nano-hydroxyapatite/chitosan/gelatin (nHA/CS/Gel) scaffolds was investigated. The outcome was assessed by histological, biochemical and morphological tests. Results indicated that hWJ-MSCs attached onto the scaffold surface through membrane filopodia, uniformly spread throughout the contacting surface. It only took 3 days for the seeded cells to appear deep inside the scaffold, reflecting proper hWJ-MSCs adhesion and migration, evidenced by both scanning electron microscope and hematoxilin and eosin assessments. Additionally, the present fabricated nHA/CS/Gel scaffold proved to be non-toxic as it supported cell proliferation measured by 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide assay. Moreover, 3-week culture of hWJ-MSCs on scaffolds, immersed in osteogenic medium, rendered the microenvironment in favor of hWJ-MSCs differentiation into osteoblast cells and extracellular matrix secretion. Finally, osteoblasts were immunologically positive for various osteogenic markers including osteocalcin, osteopontin, osteonectin, and alkaline phosphatase. Present findings indicate that nHA/CS/Gel scaffold appropriately harbored hWJ-MSCs, stimulating their growth, migration, proliferation, and differentiation. hWJ-MSCs-loaded nHA/CS/gel substitute may therefore be considered as a suitable platform for the rising demand in in vivo bone repair studies. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1166-1175, 2019.

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Native tissues orchestrate their functions by complex interdependent cascades of biochemical and biophysical cues that vary spatially and temporally during cellular processes. Scaffolds with well-tuned structural, mechanical, and biochemical properties have been developed to guide cell behavior and provide insight on cell-matrix interaction. However, static scaffolds very often fail to mimic the dynamicity of native extracellular matrices. Stimuli-responsive scaffolds have emerged as powerful platforms that capture vital features of native tissues owing to their ability to change chemical and physical properties in response to cytocompatible stimuli, thus enabling on-demand manipulation of cell microenvironment. The vast expansion in biorthogonal chemistries and stimuli-responsive functionalities has fuelled further the development of new smart scaffolds that can permit multiple irreversible or reversible spatiotemporal modulation of cell-directing cues, thereby prompting in-depth studies to interpret the decisive elements that regulate cell behavior. Integration of stimuli-responsive hydrogels with current biofabrication technologies has allowed the development of dynamic scaffolds with organizational features and hierarchical architectures similar to native tissues. This review highlights the progress achieved using stimuli-responsive hydrogels in fundamental cell biology studies, with particular emphasis on the interplay between chemistry, biomaterials design, and biofabrication technologies for manipulation of cell microenvironment.

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INTRODUCTION: The surfaces of endoosseous dental implants have been subjected to numerous modifications in order to create a surface which can provide rapid bone healing and fast implant loading. Each modification has involved changes to the chemical composition and topography of the surfaces which have resulted in various biological reactions to the implanted material. AIM: The aim of this study was to evaluate the surface topography and chemistry of various modified titanium surfaces: (1) machined surface (MA), (2) alumina-blasted (Al2O3), (3) alumina-blasted and acid-etched (Al2O3 DE), (4) hydroxyapatite/tricalcium phosphate grit-blasted (HA/TCP) and (5) hydroxyapatite/tricalcium phosphate grit-blasted and acid-etched (HA/TCP DE) and to analyse the effects of surface roughness, and chemical composition on human osteoblast vitality, differentiation, morphology and orientation. MATERIALS AND METHODS: The modified surfaces were subjected to topographic analysis using Scanning Electron Microscopy (SEM), optical profilometry, roughness analysis and chemical composition evaluation using Energy Dispersion Spectroscopy (EDS) analysis. The biological effects of the titanium modifications was analysed using human osteoblasts cell culture where the cell morphology, vitality (MTS assay) and differentiation (ALP activity) was analysed. RESULTS: The machined surfaces were classified as anisotropic, smooth and composed of titanium and oxygen. The blasted surface samples along with the blasted and etched samples were found to be isotropic and rough. The grit-blasting procedure resulted in the incorporation of components from the blasting material. In the case of the blasted and etched samples, etching decreased the surface development as indicated by the Sdr and also reduced the amount of chemical compounds incorporated into the surfaces during the blasting procedure. The attached NHOst cells, proliferated the surfaces. With regard to the MA samples, the cells spread close to the titanium surface, with expanded cytoplasmic extensions and lamelipodia and were oriented in line with the groves left after machining. On the rough substrates, cells were less dispersed and exhibited numerous cytoplasmic extensions, filopodia and interconnections, they were not oriented with respect to the surfaces features. The cell viability of all samples except for Al2O3 decreased after the first day of culture. For all Al2O3, Al2O3 DE and HA samples the viability increased with culture time after an initial reduction. At the end of the culture period the ALP activity was slightly greater on Al2O3 and HA samples compared to the control with the HA DE sample having the same activity as the control. The Al2O3, HA and HA DE ALP samples showed comparable activity and were statistically different from MA and Al2O3 DE samples. CONCLUSIONS: In this study, variously treated titanium surfaces were correlated with osteoblastic cell viability, morphology and differentiation in comparison with the plastic and smooth titanium. All examined surfaces were found to be biocompatible. Favourable cell reactions were observed for Al2O3 and HA blasted surfaces. The surface roughness patterns influenced the growth orientation while the surface topography influenced osteoblast morphology. Further animal studies are necessary to compare the in-vivo effect on osseointegration of these modified titanium surfaces.

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Fretting corrosion (or mechanically assisted corrosion, MAC) is a major corrosion mechanism in modular orthopedic implants. There is a complex interplay between fretting corrosion and the surrounding biological environment that includes particle generation and electrochemical potential excursions and currents. The goal of this work is to directly investigate the effects of fretting on cells in vitro. Using an in vitro fretting device, MC3T3 preosteoblasts were cultured onto Ti-6Al-4V disks adjacent to the fretting site. Under fretting corrosion conditions, cell viability dramatically decreased to 0.5% with the voltage drop reaching -1 V (vs. Ag/AgCl). Under the same fretting corrosion conditions, but potentiostatically holding the Ti-6Al-4V sample surface potential to -300 mV or -50 mV (vs. Ag/AgCl), the cell viability increases to 70% and 38%, respectively. The results indicate that both cathodic potential excursions and wear debris play significant roles in affecting cell viability. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 160-167, 2018.

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Recent years have seen tremendous advances in the field of hydrogel-based biomaterials. One of the most prominent revolutions in this field has been the integration of elements or techniques that enable spatial and temporal control over hydrogels' properties and functions. Here, we critically review the emerging progress of spatiotemporal control over biomaterial properties towards the development of functional engineered tissue constructs. Specifically, we will highlight the main advances in the spatial control of biomaterials, such as surface modification, microfabrication, photo-patterning, and three-dimensional (3D) bioprinting, as well as advances in the temporal control of biomaterials, such as controlled release of molecules, photocleaving of proteins, and controlled hydrogel degradation. We believe that the development and integration of these techniques will drive the engineering of next-generation engineered tissues.

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In this work, we have investigated the effects of lithium (Li) dopant at different concentrations and sintering temperatures on the physical and mechanical properties of ß-tricalcium phosphate (ß-TCP). Our results showed that Li addition at concentrations of 0.65 and 1.0 wt % inhibits the ß-TCP to α-TCP phase transformation. 0.15 wt % Li addition resulted in grain growth and extensive liquid phase was formed at higher concentrations. At 1150°C, compressive strength of ß-TCP increased from 138.7 ± 19.9 MPa to 170.9 ± 29.8 MPa with the addition of 0.15 wt % Li. Addition of higher amounts of Li decreased the compressive strength and the lowest compressive strength of 99.8 ± 13.7 MPa was found in samples containing 1.0 wt % Li. After 3 days of culture, osteoblast cells grew to confluence on samples containing 0.65 and 1.0 wt % Li. Cells grew to confluence on all doped samples after 11 days of culture and optical cell density was 4-5 folds higher on 0.15 and 1.0 wt % Li-doped TCP samples. Our results show that both Li content and sintering temperature have significant influence toward physicochemical and mechanical properties of ß-TCP which affects the osteoblast cell-materials interaction in Li-doped TCP scaffolds. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 391-399, 2017.

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Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle) levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields.

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