Cell–cell adhesion is a fundamental feature of multicellular organisms. To ensure multicellular integrity, adhesion needs to be tightly controlled and maintained. In plants, cell–cell adhesion remains poorly understood. Here, we argue that to be able to understand how cell–cell adhesion works in plants, we need to understand and quantitatively measure the mechanics behind it. We first introduce cell–cell adhesion in the context of multicellularity, briefly explain the notions of adhesion strength, work and energy and present the current knowledge concerning the mechanisms of cell–cell adhesion in plants. Because still relatively little is known in plants, we then turn to animals, but also algae, bacteria, yeast and fungi, and examine how adhesion works and how it can be quantitatively measured in these systems. From this, we explore how the mechanics of cell adhesion could be quantitatively characterised in plants, opening future perspectives for understanding plant multicellularity.

Prevascularized medical devices can improve cell therapy. Such devices may replace whole organ transplantation with hosting only the necessary therapeutic cells. We have developed a noninvasive optical technology to study the vascularization into such medical devices. In our technique, oxygen partial pressure within a device is monitored by Oxygen Sensitive Tubes (OSTs), comprising oxygen permeable silicone tubing with inner luminal surfaces coated by an oxygen-sensitive porphyrin dye. OSTs were placed within a PDMS device and transplanted into the subcutaneous space of athymic nude mice. An optical probe placed over the skin excites the OSTs with a pulse of light and detects the luminescent lifetime of emitted light, which is uniquely related to oxygen partial pressure. Furthermore, we developed a Dynamic Inhalation Gas Test (DIGT) to determine the oxygen transport rate between the microvasculature and the device. DIGT works by monitoring oxygen partial pressure in a device following a step change in inhaled-gas oxygen content. We report DIGT oxygen dynamics measured intermittently over eight weeks. Our study shows DIGT dynamics are unique to each implant, supporting the important role of the host tissue response in the availability of oxygen over time.

Dental pulp derived cells are pluripotent stem cells which can be differentiated along odontogenic, osteogenic, adipogenic, or neurogenic lineages. Odontogenic and osteogenic differentiation, in the absence of dexamethasone, have been shown to be highly dependent on substrate morphology and mechanics. Here we focus on neurogenic differentiation, using the protocol described by A. Arthur et al., and its dependence on substrate nature. DPSCs were cultured on PLA, a biodegradable polymer approved for internal use. The upregulation of genetic markers was compared with that of cells plated on standard TCP. The role of substrate morphology was investigated by plating on electrospun fibers approximately 2.0 ± 1.0 μm in diameter and on spin-cast thin films. The influence of graphene was investigated through the addition of 3% and 10% graphene nanoparticles to the films and fibers respectively.

The aspect ratio of the cells was measured using confocal microscopy. Cells grown on graphene containing substrates had larger aspect ratios than their non-graphene counterparts, and cells grown on microfibers were longer than their counterparts on the flat films. But the cell aspect ratio did not necessarily correlate with genetic differentiation. The results after 21 days of incubation indicated that early markers (TBP, β-III tubulin), decreased uniformly on all substrates relative to day 0, with the largest decrease occurring on the PLA flat film with graphene. The late stage marker, NEFM, which indicates differentiation, was upregulated to a significantly larger extent on all PLA substrates. No difference was observed between the fibers and the flat film in the absence of graphene, thus morphology did not play a significant role on this polymer. Addition of graphene did not affect the outcome on the fibers, but significantly suppressed the gene expression on the flat films. These results indicate that PLA is a promising scaffold material for neurogenic differentiation.

Scaffolds based on two different geometries were constructed by additive manufacturing: one based on a triply periodic minimal surface, the Schwarz D surface, and the other based on a rectangular geometry with orthogonal through-holes. For construction of the scaffolds, two different materials were used: polylactic acid (PLA) in filament form and alumina in printable paste form. The structure of the resulting scaffolds was characterized via X-ray diffraction and scanning electron microscopy, and cell proliferation was assessed for each geometry and material, using fluorescence microscopy and DNA quantification via NanoDrop. Additive manufacturing allowed us to obtain scaffolds with the assessed materials while guaranteeing the interconnectivity of the pores in each one. The curved surfaces constructed with PLA were more favorable for cell attachment and proliferation of the CHO-K1 cell line.

Electrospun coaxial fibers are used to create core/sheath fiber structures to act as growth-promoting scaffolds for in vitro dorsal root ganglia (DRG) cell cultures. The core was a conducting polymer, poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), and the sheath was poly-L-lactic acid (PLLA), which created coaxial fibers with a conductive core and an insulating sheath. SEM analysis confirmed the conductivity of the core and insulation of the sheath. Several coaxial spinneret designs were tested with the best results obtained by using various annular spinning needle combinations. Using a 22G/16G and 22G/17G combination, fibers with diameters of 6.1 ± 2.4 µm and 3.3 ± 0.9 µm were spun, respectively. The fibers showed a Young’s modulus and hardness of 0.16 ± 0.13 and 0.02 ± 0.01 GPa for the larger diameters, and 0.7 ± 0.4 and 0.03 ± 0.03 GPa for the smaller diameter fibers. In vitro test cultures showed the fibers successfully directed chick DRG axonal outgrowth with low biotoxicity.

This article provides an overview of emerging directions in the materials science of biointegrated electronic and microfluidic systems, as defined by technologies that are capable of supporting long-term, intimate, physical interfaces to living organisms. Here, deterministic hard/soft composite structures, including those that leverage concepts in fractal mathematics, serve as the materials foundations for diverse devices of this type. Examples of “epidermal” or skin-like electronic systems for biophysical tracking of patient conditions that range from stroke to hydrocephalus illustrate the engineering maturity and operational sophistication that is now possible. Recent ideas in soft, skin-mounted, microfluidic lab-on-a-chip systems extend the capabilities of such platforms to include biochemical assessments of physiological status via capture, storage, manipulation, and in situ detection of biomarkers in microliter volumes of sweat, collected as it emerges from the surface of the skin. The article concludes with a description of mechanically guided assembly schemes that provide access to three-dimensional, open-mesh constructs, as a frontier area of materials development in this broader area of biointegrated systems.

The dysfunctional metabolism of glucose in cancer cells represents a new avenue for cancer targeting based on sugar-derived carriers. Here, glucose-derived carbon spheres (CS) were prepared through a simple hydrothermal method, yielding highly homogenous spherical particles that exhibited excellent stability in aqueous solution. The abundant presence of surface hydroxyl functionalities was used for a subsequent condensation of an amino silane that was the basis for further covalent coupling strategies. CS were modified with a cyclooctyne derivative providing a highly selective binding site for copper-free click reactions. Moreover, the surface modification of CS with a dye-label allowed for their intracellular detection revealing a preferential uptake of CS, compared to silica particles, in tumor cells. These results thus demonstrate the highly promising potential of glucose-derived particles for tumor targeting applications and their efficient surface modification.

Eggshell Membrane (ESM) is a naturally occurring proteinaceous microfibrous scaffold capable of mimicking the extracellular matrix (ECM). The extraction methodology deployed for its extraction process impedes its extensive application as a biomaterial in regenerative medicine. Herein, a unique route was deployed to decorate the surface of ESM with electrospun polycaprolactone (PCL) nanofiber in order to ameliorate the above problems and also fabricate a novel ECM mimicking bilayered scaffold for skin tissue engineering applications. Microstructural and surface topographic analysis confirms the formation of bilayered structure with smooth electrospun PCL nanofibers decorated on ESM. Carbodiimide chemistry was utilized to crosslink the two layers. Cytocompatibility evaluation of scaffolds was carried out with Human dermal fibroblast (HDF) cells. The biomimetic architecture and protein rich composition of as fabricated bilayered construct facilitated extensive cell adhesion, proliferation and migration in contrast the bare natural tissue led to impeded cell adhesion.

There is growing evidence that minimizing the mechanical mismatch between neural implants and brain tissue mitigates inflammatory, biological responses at the interface under long-term implant conditions. The goal of this study is to develop a brain-like soft, conductive neural interface and use an improvised, penetrating microindentation technique reported by us earlier to quantitatively assess the (a) elastic modulus of the neural interface after implantation, (b) mechanical stresses during penetration of the probe, and (c) periodic stresses at steady-state due to tissue micromotion around the probe. We fabricated poly- dimethylsiloxane (PDMS) matrices with multi-walled carbon nanotubes (MWCNTs) using two distinct but carefully calibrated cross-linking ratios, resulting in hard (elastic modulus∼484 kPa) or soft, brain-like (elastic modulus∼5.7 kPa) matrices, the latter being at least 2 orders of magnitude softer than soft neural interfaces reported so far. Subsequent loading of the hard and soft silicone based matrices with (100% w/w) low-molecular weight PDMS siloxanes resulted in further decrease in the elastic modulus of both matrices. Carbon probes with soft PDMS coating show significantly less maximum axial forces (-587 ± 51.5 µN) imposed on the brain than hard PDMS coated probes (-1,253 ± 252 µN) during and after insertion. Steady-state, physiological micromotion related stresses were also significantly less for soft- PDMS coated probes (55.5 ± 17.4 Pa) compared to hard-PDMS coated probes (141.0 ± 21.7 Pa). The penetrating microindentation technique is valuable to quantitatively assess the mechanical properties of neural interfaces in both acute and chronic conditions.

Tissue Engineering has been studied to develop tissues as an alternative approach to the organ regeneration. Successful artificial tissue growth in regenerative medicine depends on the precise scaffold fabrication as well as the cell-cell and cell-scaffold interaction. Scaffolds are extracellular matrices that guide cells to grow in 3D to regenerate the tissues. Cell-seeded scaffolds must be implanted to the damaged tissues to do the tissue regeneration. Scaffolds’ mechanical properties and porosities are the two main scaffold fabrication parameters as the scaffolds must be able to hold the pressure due to the surrounding tissues after the implantation process. In this research, scaffolds were fabricated by photolithography and Poly(ethylene glycol) Diacrylate (PEGDA) which is a biocompatible and biodegradable material was used as a fabrication material. In order to compare the compressive properties of PEGDA only with the compressive properties of drug delivered PEGDA, firstly, PEGDA only solutions were prepared. Then, PEGDA was mixed with Meloxicam 15 mg, Hydrochlorothiazide 12.5 mg, Cyclobenzaprine 10 mg and Spironolactone-hctz 25-25 mg respectively and they were placed under the UV light for about 15 minutes to solidify the cylindrical shaped hydrogels. 5 samples from each group were fabricated under the same conditions. Laboratory temperature, photoinitiator concentration and UV light intensity was kept constant during the fabrication process. After the fabrication was completed, Instron 3369 universal mechanical testing machine with the 5 mm/min compression rate was used to do the compression tests to compare the drug effects on PEGDA hydrogels. Our results indicate that average ultimate strength of PEGDA only samples was 3.820 MPa. Also, due to the fact that Meloxicam 15 mg and PEGDA mixture did not solidify under the UV light at all, compression test could not be performed for PEGDA- Meloxicam 15 mg mixture. However, Hydrochlorothiazide 12.5 mg, Cyclobenzaprine 10 mg and Spironolactone-hctz 25-25 mg dissolved within the PEGDA completely and our compression results show that average ultimate strengths were 3.372 MPa, 1.602 MPa, 1.999 MPa respectively. This preliminary research showcases that compressive properties of the PEGDA-based photopolymerized scaffolds can be altered with the control of the drug type and drug concentration.

Magnesium (Mg)-based biomaterials have attracted increasing attention in biomedical applications, such as orthopaedic, cardiovascular, urological, and neural applications because of the biocompatibility, biodegradability, antibacterial properties, and excellent mechanical properties. However, rapid degradation of Mg is the major concern for many clinical applications. Alloying Mg with other elements and engineering proper surfaces are the two approaches to control the degradation of Mg-based biomaterials. Our lab has investigated several classes of Mg-based biodegradable alloys and various surface treatment methods for medical implant and device applications. This mini-review highlights key research progress on Mg-based biomaterials and suggests future directions for Mg-based biomaterials.

Three-dimensional (3D) printing has expanded beyond the mere patterned deposition of melted solids, moving into areas requiring spatially structured soft matter—typically materials composed of polymers, colloids, surfactants, or living cells. The tunable and dynamically variable rheological properties of soft matter enable the high-resolution manufacture of soft structures. These rheological properties are leveraged in 3D printing techniques that employ sacrificial inks and sacrificial support materials, which go through reversible solid–fluid transitions under modest forces or other small perturbations. Thus, a sacrificial material can be used to shape a second material into a complex 3D structure, and then discarded. Here, we review the sacrificial materials and related methods used to print soft structures. We analyze data from the literature to establish manufacturing principles of soft matter printing, and we explore printing performance within the context of instabilities controlled by the rheology of soft matter materials.

The holy grail of regenerative technologies is to regrow a limb. This grand challenge requires us to develop truly innovative strategies and toolboxes across advanced materials science, stem cell science, physics, and developmental biology, and converge these advancements to address the limitations of wound healing and harness the regenerative capacity in humans. We discuss the convergence approach put forward by the field of regenerative engineering to develop translational strategies involving electrically conductive and novel polymers, stem cells, high-throughput technologies, and nanotechnology to regenerate the limb.

Three-dimensional (3D) bioprinting has become a fast-developing research field in the last few years. Many different technical solutions are available, with extrusion-based printing being the most promising and versatile method. In addition, a variety of biomaterials are already available for 3D printing of live cells. The real challenge, however, remains bioprinting of macroscopic, volumetric constructs of well-defined structures since hydrogels used for cell-embedding must consist of rather soft materials. This article describes recent developments to overcome these limitations that prevent clinical applications of bioprinted human tissues. New approaches include technical solutions such as in situ cross-linking or gelation processes that now can be performed during the bioprinting process, modified bioinks that combine suitable viscosity and cytocompatible gelation mechanisms, and utilization of additional materials to provide mechanical strength to the cell-laden constructs.

Multimaterial bioprinting technologies offer promising avenues to create mini-organ models with enhanced tissue heterogeneity and complexity. This article focuses on the application of three-dimensional bioprinting to fabricate organ-on-a-chip systems for in vitro drug testing and screening. We illustrate the capabilities and limitations of a bioprinting approach compared to microfabrication in constructing an organ-on-a-chip device. Further, we propose strategies in multimaterial integration for printing microphysiological tissue models. With these analyses, key challenges and future directions are highlighted.

“Bottom-up” assembly of fully functional cell-based materials has enormous potential for replicating endogenous tissues. Currently, most tissue-engineering strategies are based on incorporating dissociated cells into an artificial three-dimensional matrix of supportive structural elements that direct cellular migration, proliferation, and organization. The matrix provides “top-down” guidance cues that impose assembly directions on the cells; however, the matrix also competes for space and limits fully functional, cell-dense tissues. This article focuses on bottom-up fabrication of functional tissue by cell sheet engineering. Cell sheet engineering is based on the sequential stacking and adhesion of confluent and organized cell monolayers from two-dimensional cell culture without the need for artifical scaffolds or structural intermediates. The resulting functional cellular monolayers (either individually or as stacked sheets) can then be directly implanted into living systems. Clinical successes are highlighted as well as attempts to overcome the vascularization limit often observed in engineered tissues.

Bioactive glasses and related bioactive glass-ceramics have been used for over three decades in biomedical applications such as bulk, particulate, or coatings materials. More recently, highly porous bioactive glass-ceramic scaffolds for bone-tissue engineering have also been developed from selected compositions of bioactive glasses. Current bioactive glass-ceramic scaffolds are characterized by an open porous network, high bioactivity, and mechanical properties similar to those of trabecular bone. This article reviews the latest achievements in the development of porous bioactive glass-ceramics intended for bone-tissue engineering applications, highlighting the fabrication technologies and scaffold properties. Improvements in the mechanical properties of bioactive glass-ceramic scaffolds exhibiting high bioactivity have been achieved by different approaches in the last 10 years. Relevant long-term in vivo studies are required to confirm the suitability of such bioactive glass-ceramic scaffolds in clinical applications.

In today’s technology, organ transplantation is found very challenging as it is not easy to find the right donor organ in a short period of time. In the last several decades, tissue engineering was rapidly developed to be used as an alternative approach to the organ transplantation. Tissue engineering aims to regenerate the tissues and also organs to help patients who waits for the organ transplantation. Recent research showed that in order to regenerate the tissues, cells must be seeded onto the 3D artificial laboratory fabricated matrices called scaffolds. If cells show healthy growth within the scaffolds, they can be implanted to the injured tissue to do the regeneration. One of the biggest limitation that reduces the success rate of tissue regeneration is the fabrication of accurate thick 3D scaffolds. In this research “maskless photolithography” was used to fabricate the scaffolds. Experiment setup consist of digital micro-mirror devices (DMD) (Texas Instruments, DLi4120), optical lens sets, UV light source (DYMAX, BlueWave 200) and PEGDA which is a liquid form photo-curable solution. In this method, scaffolds are fabricated in layer-by-layer fashion to control the interior architecture of the scaffolds. Working principles of the maskless photolithography is, first layer shape is designed with AutoCAD and the designed image is uploaded to the DMD as a bitmap file. DMD consists of hundreds of tiny micro-mirrors. When the UV light is turned on and irradiated the DMD, depending on the micro-mirrors’ angles, UV light is selectively reflected to the low percentage Polyethylene (glycol) Diacrylate (PEGDA) photo-curable solution. When UV light penetrates into the PEGDA, only the illuminated part is solidified and non-illuminated area still remains in the liquid phase. In this research, scaffolds were fabricated in three layers. First layer and the last layer are solid layers and y-shape open structure was sandwiched between these layers. After the first layer is fabricated with DMD, a “y-shape” structure was fabricated with the 3D printer by using the dissolvable filament. Then, it was placed onto the first solid layer and covered with fresh high percentage PEGDA solution. UV light was reflected to the PEGDA solution and solidified to make the second and third layers. After the scaffold was fabricated, it is dipped into the limonene solution to dissolve the y-shape away. Our results show that thick scaffolds can be fabricated in layer-by-layer fashion with “maskless photolithography”. Since the UV light is stable and does not move onto the PEGDA, entire scaffold can be fabricated in one single UV shot which makes the process faster than the current fabrication techniques.