Bioprinted High-Cell-Density Laminar Scaffolds Stimulate Extracellular Matrix Production in Osteochondral Co-Cultures.

Many tissues have a laminar structure, but there are limited technologies for establishing laminar co-cultures for in vitro testing. Here, we demonstrate that collagen-alginate-fibrin (CAF) hydrogel scaffolds produced using the reactive jet impingement bioprinting technique can produce osteochondral laminar co-cultures with well-defined interfaces between cell types and high cell densities to support cell-cell interaction across the interfaces. The influence of cell density and the presence of the two cell types on the production of extracellular matrix (ECM) and the emergent mechanical properties of gels is investigated using IHC, ELISA, gel mass, and the compression modulus.

Manufacturing of 3D-Printed Hybrid Scaffolds with Polyelectrolyte Multilayer Coating in Static and Dynamic Culture Conditions.

Three-dimensional printing (3DP) has emerged as a promising method for creating intricate scaffold designs. This study assessed three 3DP scaffold designs fabricated using biodegradable poly(lactic) acid (PLA) through fused deposition modelling (FDM): mesh, two channels (2C), and four channels (4C). To address the limitations of PLA, such as hydrophobic properties and poor cell attachment, a post-fabrication modification technique employing Polyelectrolyte Multilayers (PEMs) coating was implemented.

Bioinspired Collagen/Hyaluronic Acid/Fibrin-Based Hydrogels for Soft Tissue Engineering: Design, Synthesis, and In Vitro Characterization.

A major challenge for future drug development comprises finding alternative models for drug screening. The use of animal models in research is highly controversial, with an ongoing debate on their ethical acceptability. Also, animal models are often poorly predictive of therapeutic outcomes due to the differences between animal and human physiological environments.

Electromechanical Coupling in Collagen Measured under Increasing Relative Humidity.

The functional role of collagen piezoelectricity has been under debate since the discovery of piezoelectricity in bone in 1957. The possibility that piezoelectricity plays a role in bone remodeling has generated interest in the investigation of this effect in relevant physiological conditions; however, there are conflicting reports as to whether collagen is piezoelectric in a humid environment. In macroscale measurements, the piezoelectricity in hydrated tendon has been shown to be insignificant compared to dehydrated tendon, whereas, at the nanoscale, the piezoelectric effect has been observed in both dry and wet bone using piezoresponse force microscopy (PFM).

Cell seeding via bioprinted hydrogels supports cell migration into porous apatite-wollastonite bioceramic scaffolds for bone tissue engineering.

Cell seeding via cell-laden hydrogels offers a rapid way of depositing cells onto a substrate or scaffold. When appropriately formulated, hydrogels provide a dense network of fibres for cellular encapsulation and attachment, creating a protective environment that prevents cells to be washed away by media. However, when incorporating hydrogels into a cell seeding strategy the cellular capacity for migration from a hydrogel network and subsequent biofunctionality must be assessed.

Effective Endotoxin Removal from Chitosan That Preserves Chemical Structure and Improves Compatibility with Immune Cells.

Chitosan is one of the most researched biopolymers for healthcare applications, however, being a naturally derived polymer, it is susceptible to endotoxin contamination, which elicits pro-inflammatory responses, skewing chitosan's performance and leading to inaccurate conclusions. It is therefore critical that endotoxins are quantified and removed for in vivo use. Here, heat and mild NaOH treatment are investigated as facile endotoxin removal methods from chitosan.

Advances in biomimetic collagen mineralisation and future approaches to bone tissue engineering.

With an ageing world population and ~20% of adults in Europe being affected by bone diseases, there is an urgent need to develop advanced regenerative approaches and biomaterials capable to facilitate tissue regeneration while providing an adequate microenvironment for cells to thrive. As the main components of bone are collagen and apatite mineral, scientists in the tissue engineering field have attempted in combining these materials by using different biomimetic approaches to favour bone repair. Still, an ideal bone analogue capable of mimicking the distinct properties (i.

Adhesive Bioinspired Coating for Enhancing Glass-Ceramics Scaffolds Bioactivity.

Bioceramic scaffolds, composed of a biphasic composite containing bioactive glass and hydroxyapatite, were prepared in this work to overcome the intrinsic limits of the two components taken separately (in particular, their specific reactivities and dissolution rates, which should be tunable as a function of the given clinical requirements). To mimic the biological environment and tune the different stages of cellular response, a coating with gelatin and chondroitin sulphate via Layer-by-Layer (LbL) assembly was presented and discussed. The resulting functionalized scaffolds were affected by the coating in terms of microstructure and porosity.

Interplay between biomaterials and the immune system: Challenges and opportunities in regenerative medicine.

The use of biomaterials for tissue engineering and regenerative medicine applications has increased dramatically over recent years. However, the clinical uptake of a wide variety of biomaterials remains limited due to adverse effects commonly exhibited by patients, which are caused by the host immune response. Despite this, current in vitro evaluation standards (ISO-10993) for assessing the host response to biomaterials have limitations in predicting the likelihood of in vivo biomaterial acceptance.

Bioprinting of Cell-Laden Hydrogels onto Titanium Alloy Surfaces to Produce a Bioactive Interface.

The surface of metal implants serves as a powerful signaling cue for cells. Its properties play an essential role in stabilizing the bone-implant interface and facilitating the early osseointegration by encouraging bone deposition on the surface. However, effective strategies to deliver cells to the metal surfaces are yet to be explored.

Microvalve Bioprinting of MSC-Chondrocyte Co-Cultures.

Recent improvements within the fields of high-throughput screening and 3D tissue culture have provided the possibility of developing in vitro micro-tissue models that can be used to study diseases and screen potential new therapies. This paper reports a proof-of-concept study on the use of microvalve-based bioprinting to create laminar MSC-chondrocyte co-cultures to investigate whether the use of MSCs in ACI procedures would stimulate enhanced ECM production by chondrocytes. Microvalve-based bioprinting uses small-scale solenoid valves (microvalves) to deposit cells suspended in media in a consistent and repeatable manner.

Hydrogels of engineered bacterial fimbriae can finely tune 2D human cell culture.

Demand continues to grow for biomimetic materials able to create well-defined environments for modulating the behaviour of living cells in culture. Here, we describe hydrogels based upon the polymeric bacterial fimbriae protein capsular antigen fragment 1 (Caf1) that presents tunable biological properties for enhanced tissue cell culture applications. We demonstrate how Caf1 hydrogels can regulate cellular functions such as spreading, proliferation and matrix deposition of human dermal fibroblast cells (hDFBs).

Development of Natural-Based Bone Cement for a Controlled Doxorubicin-Drug Release.

Osteosarcoma (OS) accounts for 60% of all global bone cancer diagnoses. Intravenous administration of Doxorubicin Hydrochloride (DOXO) is the current form of OS treatment, however, systemic delivery has been linked to the onset of DOXO induced cardiomyopathy. Biomaterials including calcium phosphate cements (CPCs) and nanoparticles (NPs) have been tested as localized drug delivery scaffolds for OS cells.

Reliable inkjet printing of chondrocytes and MSCs using reservoir agitation.

Drop-on-demand (DoD) inkjet printing has been explored for a range of applications, including those to selectively deposit cellular material, due to the high accuracy and scalability of such systems when compared with alternative bioprinting techniques. Despite this, there remain considerable limitations when handling cell suspensions due to the agglomeration and sedimentation of cells during printing, leading to a deterioration in jetting performance. The objective of this work was to design and assess the effectiveness of a custom agitation system to maintain cellular dispersion within the ink reservoir during printing.

A Comparison of Osteoblast and Osteoclast In Vitro Co-Culture Models and Their Translation for Preclinical Drug Testing Applications.

As the population of western societies on average ages, the number of people affected by bone remodeling-associated diseases such as osteoporosis continues to increase. The development of new therapeutics is hampered by the high failure rates of drug candidates during clinical testing, which is in part due to the poor predictive character of animal models during preclinical drug testing. Co-culture models of osteoblasts and osteoclasts offer an alternative to animal testing and are considered to have the potential to improve drug development processes in the future.

Short phosphate glass fiber - PLLA composite to promote bone mineralization.

The clinical application of composites seeks to exploit the mechanical and chemical properties of materials which make up the composite, and in researching polymer composites for biomedical applications the aim is usually to enhance the bioactivity of the polymer, while maintaining the mechanical properties. To that end, in this study medical grade Poly(L-lactic) acid (PLLA) has been reinforced with short phosphate-based glass fibers (PGF). The materials were initially mixed by melting PLLA granules with the short fibers, before being extruded to form a homogenous filament, which was pelletized and used as feedstock for compression moulding.

Multilayer nanoscale functionalization to treat disorders and enhance regeneration of bone tissue.

The coatings application onto medical devices has experienced a continuous growth in the last few years. Medical device coating market is expected to grow at a CAGR of 5.16% to reach USD 10 million by 2023 due to the increasing geriatric population and the growing demand for continuous innovation.

Reactive jet impingement bioprinting of high cell density gels for bone microtissue fabrication.

Advances in three-dimensional cell cultures offer new opportunities in biomedical research and drug development. However, there are still challenges to overcome, including the lack of reliability, repeatability and complexity of tissues obtained by these techniques. In this study, we describe a new bioprinting system called reactive jet impingement (ReJI) for the bioprinting of cell-laden hydrogels.

Recent Approaches to the Manufacturing of Biomimetic Multi-Phasic Scaffolds for Osteochondral Regeneration.

Cartilage lesions of the knee are common disorders affecting people of all ages; as the lesion progresses, it extends to the underlying subchondral bone and an osteochondral defect appears. Osteochondral (OC) tissue compromises soft cartilage over hard subchondral bone with a calcified cartilage interface between these two tissues. Osteochondral defects can be caused by numerous factors such as trauma and arthritis.

Polyelectrolyte multi-layers assembly of SiCHA nanopowders and collagen type I on aminolysed PLA films to enhance cell-material interactions.

This paper presents a new approach in assembling bone extracellular matrix components onto PLA films, and investigates the most favourable environment which can be created using the technique for cell-material interactions. Poly (lactic acid) (PLA) films were chemically modified by covalently binding the poly(ethylene imine) (PEI) as to prepare the substrate for immobilization of polyelectrolyte multilayers (PEMs) coating. Negatively charged polyelectrolyte consists of well-dispersed silicon-carbonated hydroxyapatite (SiCHA) nanopowders in hyaluronic acid (Hya) was deposited onto the modified PLA films followed by SiCHA in collagen type I as the positively charged polyelectrolyte.