A Tympanic Piezo-Bioreactor Modulates Ion Channel-Associated Mechanosignaling to Stabilize Phenotype and Promote Tenogenesis in Human Tendon-Derived Cells.

Preserving the function of human tendon-derived cells (hTDCs) during cell expansion is a significant challenge in regenerative medicine. In this study, a non-genetic approach is introduced to control the differentiation of hTDCs using a newly developed tympanic bioreactor. The system mimics the functionality of the human tympanic membrane, employing a piezoelectrically tuned acoustic diaphragm made of polyvinylidene fluoride-co-trifluoroethylene and boron nitride nanotubes.

Modification of Living Diatom, , with a Calcium Precursor through a Calcium Uptake Mechanism: A Next Generation Biomaterial for Advanced Delivery Systems.

The diatom's frustule, characterized by its rugged and porous exterior, exhibits a remarkable biomimetic morphology attributable to its highly ordered pores, extensive surface area, and unique architecture. Despite these advantages, the toxicity and nonbiodegradable nature of silica-based organisms pose a significant challenge when attempting to utilize these organisms as nanotopographically functionalized microparticles in the realm of biomedicine. In this study, we addressed this limitation by modulating the chemical composition of diatom microparticles by modulating the active silica metabolic uptake mechanism while maintaining their intricate three-dimensional architecture through calcium incorporation into living diatoms.

Physicochemical cues are not potent regulators of human dermal fibroblast trans-differentiation.

Due to their inherent plasticity, dermal fibroblasts hold great promise in regenerative medicine. Although biological signals have been well-established as potent regulators of dermal fibroblast function, it is still unclear whether physiochemical cues can induce dermal fibroblast trans-differentiation. Herein, we evaluated the combined effect of surface topography, substrate rigidity, collagen type I coating and macromolecular crowding in human dermal fibroblast cultures.

The synergistic effect of physicochemical in vitro microenvironment modulators in human bone marrow stem cell cultures.

Modern bioengineering utilises biomimetic cell culture approaches to control cell fate during in vitro expansion. In this spirit, herein we assessed the influence of bidirectional surface topography, substrate rigidity, collagen type I coating and macromolecular crowding (MMC) in human bone marrow stem cell cultures. In the absence of MMC, surface topography was a strong modulator of cell morphology.

A Self-Powered Piezo-Bioelectric Device Regulates Tendon Repair-Associated Signaling Pathways through Modulation of Mechanosensitive Ion Channels.

Tendon disease constitutes an unmet clinical need and remains a critical challenge in the field of orthopaedic surgery. Innovative solutions are required to overcome the limitations of current tendon grafting approaches, and bioelectronic therapies show promise in treating musculoskeletal diseases, accelerating functional recovery through the activation of tissue regeneration-specific signaling pathways. Self-powered bioelectronic devices, particularly piezoelectric materials, represent a paradigm shift in biomedicine, negating the need for battery or external powering and complementing existing mechanotherapy to accelerate the repair processes.

Laser-Induced Periodic Surface Structure Enhances Neuroelectrode Charge Transfer Capabilities and Modulates Astrocyte Function.

The brain machine interface (BMI) describes a group of technologies capable of communicating with excitable nervous tissue within the central nervous system (CNS). BMIs have seen major advances in recent years, but these advances have been impeded because of a temporal deterioration in the signal to noise ratio of recording electrodes following insertion into the CNS. This deterioration has been attributed to an intrinsic host tissue response, namely, reactive gliosis, which involves a complex series of immune mediators, resulting in implant encapsulation via the synthesis of pro-inflammatory signaling molecules and the recruitment of glial cells.

PEDOT:PSS interfaces stabilised using a PEGylated crosslinker yield improved conductivity and biocompatibility.

The rapidly expanding fields of bioelectronics, and biological interfaces with electronic sensors and stimulators, are placing an increasing demand on candidate materials to serve as robust surfaces that are both biocompatible, stable and electroconductive. Amongst conductive polymers, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a promising material in biomedical research due to its appropriate stability and high conductivity, however its intrinsic solubility requires a crosslinking process that can limit its conductivity and biocompatibility. Poly(ethylene glycol) is known to be a suitably anti-immunogenic moiety and its derivatives have been widely used for biomedical applications.

Nanocellulose reinforced gellan-gum hydrogels as potential biological substitutes for annulus fibrosus tissue regeneration.

Intervertebral disc (IVD) degeneration is associated with both structural damage and aging related degeneration. Annulus fibrosus (AF) defects such as annular tears, herniation and discectomy require novel tissue engineering strategies to functionally repair AF tissue. An ideal construct will repair the AF by providing physical and biological support, facilitating regeneration.

Polyhydroxyalkanoate/carbon nanotube nanocomposites: flexible electrically conducting elastomers for neural applications.

Aim: Medium chain length-polyhydroxyalkanoate/multi-walled carbon nanotube (MWCNTs) nanocomposites with a range of mechanical and electrochemical properties were fabricated via assisted dispersion and solvent casting, and their suitability as neural interface biomaterials was investigated.

Materials & Methods: Mechanical and electrical properties of medium chain length-polyhydroxyalkanoate/MWCNTs nanocomposite films were evaluated by tensile test and electrical impedance spectroscopy, respectively. Primary rat mesencephalic cells were seeded on the composites and quantitative immunostaining of relevant neural biomarkers, and electrical stimulation studies were performed.

Responsive Biomaterials: Advances in Materials Based on Shape-Memory Polymers.

Shape-memory polymers (SMPs) are morphologically responsive materials with potential for a variety of biomedical applications, particularly as devices for minimally invasive surgery and the delivery of therapeutics and cells for tissue engineering. A brief introduction to SMPs is followed by a discussion of the current progress toward the development of SMP-based biomaterials for clinically relevant biomedical applications.

Advances in Functional Assemblies for Regenerative Medicine.

The ability to synthesise bioresponsive systems and selectively active biochemistries using polymer-based materials with supramolecular features has led to a surge in research interest directed towards their development as next generation biomaterials for drug delivery, medical device design and tissue engineering.

Harnessing Hierarchical Nano- and Micro-Fabrication Technologies for Musculoskeletal Tissue Engineering.

Cells within a tissue are able to perceive, interpret and respond to the biophysical, biomechanical, and biochemical properties of the 3D extracellular matrix environment in which they reside. Such stimuli regulate cell adhesion, metabolic state, proliferation, migration, fate and lineage commitment, and ultimately, tissue morphogenesis and function. Current scaffold fabrication strategies in musculoskeletal tissue engineering seek to mimic the sophistication and comprehensiveness of nature to develop hierarchically assembled 3D implantable devices of different geometric dimensions (nano- to macrometric scales) that will offer control over cellular functions and ultimately achieve functional regeneration.

Effects of Polydopamine Functionalization on Boron Nitride Nanotube Dispersion and Cytocompatibility.

Boron nitride nanotubes (BNNTs) have unique physical properties, of value in biomedical applications; however, their dispersion and functionalization represent a critical challenge in their successful employment as biomaterials. In the present study, we report a process for the efficient disentanglement of BNNTs via a dual surfactant/polydopamine (PD) process. High-resolution transmission electron microscopy (HR-TEM) indicated that individual BNNTs become coated with a uniform PD nanocoating, which significantly enhanced dispersion of BNNTs in aqueous solutions.

Nanoscale neuroelectrode modification via sub-20 nm silicon nanowires through self-assembly of block copolymers.

Neuroprosthetic technologies for therapeutic neuromodulation have seen major advances in recent years but these advances have been impeded due to electrode failure or a temporal deterioration in the device recording or electrical stimulation potential. This deterioration is attributed to an intrinsic host tissue response, namely glial scarring or gliosis, which prevents the injured neurons from sprouting, drives neurite processes away from the neuroelectrode and increases signal impedance by increasing the distance between the electrode and its target neurons. To address this problem, there is a clinical need to reduce tissue encapsulation of the electrodes in situ and improve long-term neuroelectrode function.

Biomimetic approaches in bone tissue engineering: Integrating biological and physicomechanical strategies.

The development of responsive biomaterials capable of demonstrating modulated function in response to dynamic physiological and mechanical changes in vivo remains an important challenge in bone tissue engineering. To achieve long-term repair and good clinical outcomes, biologically responsive approaches that focus on repair and reconstitution of tissue structure and function through drug release, receptor recognition, environmental responsiveness and tuned biodegradability are required. Traditional orthopedic materials lack biomimicry, and mismatches in tissue morphology, or chemical and mechanical properties ultimately accelerate device failure.

Diatoms: a biotemplating approach to fabricating drug delivery reservoirs.

Biotemplating is a rapidly expanding subfield that utilizes nature-inspired systems and structures to create novel functional materials, and it is through these methods that the limitations of current engineering practices may be advanced. The diatom is an exceptional template for drug delivery applications, owing largely to its highly-ordered pores, large surface area, species-specific architecture, and flexibility for surface modifications. Diatoms have been studied in a wide range of biomedical applications and their potential as the next frontier of drug delivery has yet to be fully exploited.

Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces: the role of focal adhesion maturation.

The differentiation of progenitor cells is dependent on more than biochemical signalling. Topographical cues in natural bone extracellular matrix guide cellular differentiation through the formation of focal adhesions, contact guidance, cytoskeletal rearrangement and ultimately gene expression. Osteoarthritis and a number of bone disorders present as growing challenges for our society.

Biofunctionalisation of electrically conducting polymers.

During a single decade of research, evidence has emerged that glial scar formation around the electro-tissue interface drives neural loss and increases the signal impedance of the electrodes, compromising the efficiency of the stimulating systems. Studies with conducting polymers (CPs) as electrode coatings have shown enhanced tissue integration and electrode performance in situ through biochemical and physicomechanical functionalisation. In this review, recent findings on CP modifications are provided in the context of neurospecific biomaterials, shedding light on the valuable impact of multifunctionalised strategies for biomedical applications.

The role of microtopography in cellular mechanotransduction.

Mechanotransduction is crucial for cellular processes including cell survival, growth and differentiation. Topographically patterned surfaces offer an invaluable non-invasive means of investigating the cell response to such cues, and greater understanding of mechanotransduction at the cell-material interface has the potential to advance development of tailored topographical substrates and new generation implantable devices. This study focuses on the effects of topographical modulation of cell morphology on chromosomal positioning and gene regulation, using a microgrooved substrate as a non-invasive mechanostimulus.

Nanotopographical control of stem cell differentiation.

Stem cells have the capacity to differentiate into various lineages, and the ability to reliably direct stem cell fate determination would have tremendous potential for basic research and clinical therapy. Nanotopography provides a useful tool for guiding differentiation, as the features are more durable than surface chemistry and can be modified in size and shape to suit the desired application. In this paper, nanotopography is examined as a means to guide differentiation, and its application is described in the context of different subsets of stem cells, with a particular focus on skeletal (mesenchymal) stem cells.

Using immuno-scanning electron microscopy for the observation of focal adhesion-substratum interactions at the nano- and microscale in S-phase cells.

It is becoming clear that the nano/microtopography of a biomaterial in vivo is of first importance in influencing focal adhesion formation and subsequent cellular behaviour. When considering next-generation biomaterials, where the material's ability to elicit a regulated cell response will be key to device success, focal adhesion analysis is an useful indicator of cytocompatibility and can be used to determine functionality. Here, a methodology is described to allow simultaneous high-resolution imaging of focal adhesion sites and the material topography using field emission scanning electron microscopy.

Nanotopographical modification: a regulator of cellular function through focal adhesions.

Unlabelled: As materials technology and the field of biomedical engineering advances, the role of cellular mechanisms, in particular adhesive interactions with implantable devices, becomes more relevant in both research and clinical practice. A key tenet of medical device design has evolved from the exquisite ability of biological systems to respond to topographical features or chemical stimuli, a process that has led to the development of next-generation biomaterials for a wide variety of clinical disorders. In vitro studies have identified nanoscale features as potent modulators of cellular behavior through the onset of focal adhesion formation.

The use of nanoscale topography to modulate the dynamics of adhesion formation in primary osteoblasts and ERK/MAPK signalling in STRO-1+ enriched skeletal stem cells.

The physiochemical characteristics of a material with in vivo applications are critical for the clinical success of the implant and regulate both cellular adhesion and differentiated cellular function. Topographical modification of an orthopaedic implant may be a viable method to guide tissue integration and has been shown in vitro to dramatically influence osteogenesis, inhibit bone resorption and regulate integrin mediated cell adhesion. Integrins function as force dependant mechanotransducers, acting via the actin cytoskeleton to translate tension applied at the tissue level to changes in cellular function via intricate signalling pathways.