Bioreactors for Tissue Engineering: An Update

One of the greatest puzzles in wound healing is how to substitute or replace the defect caused by loss and damaged tissue or organs. In regenerative medicine, Tissue Engineering has been proposed to supply this demand by generating tissues in vitro. Bioreactors are the key to translate these cells and tissue-based constructs into large-scale biological products that are clinically effective, safe and financially pliable. In this review, we summarise the different up-to-date bioreactor designs being used for different cell types and special design scaffolds, and highlight advantages of different bioreactors, current challenges and the future trends. It is our belief that with efforts combined from multiple disciplinary participants, a novel bioreactor system that is capable of fast, large scale tissue culture would come about in near future

Chemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineages

Human adipose derived stem cells (ADSCs) are being explored for the repair of craniofacial defects due to their multi-differentiation potential and ease of isolation and expansion. Crucial to using ADSCs for craniofacial repair is the availability of materials with appropriate biomechanical properties that can support their differentiation into bone and cartilage. We tested the hypothesis that different modifications of chemical groups on the surface of a nanocomposite polymer could increase human ADSC adhesion and selectively enhance their osteogenic and chondrogenic differentiation. We show that the COOH modification significantly promoted initial cell adhesion and proliferation over 14 days compared to NH2 surfaces. Expression of focal adhesion kinase and vinculin was enhanced after plasma surface polymerization at 24 hours. The COOH modification significantly enhanced chondrogenic differentiation as indicated by up-regulation of aggrecan and collagen II transcripts. In contrast, NH2 group functionalised scaffolds promoted osteogenic differentiation with significantly enhanced expression of collagen I, allkaline phosphatase and osteocalcin both at the gene and protein level. Finally, chorioallantoic membrane grafting demonstrated that both NH2 and COOH functionalised scaffolds seeded with ADSCs were biocompatible and supported vessel ingrowth apparently to a greater degree than unmodified scaffolds. In summary, our study shows the ability to direct ADSC chondrogenic and osteogenic differentiation by deposition of different chemical groups through plasma surface polymerization. Hence this approach could be used to selectively enhance bone or cartilage formation before implantation in vivo to repair skeletal defects

Applications of nanomaterials in mechano-sensitive tissues

Bone, cartilage and tendon defects have specific structural, chemical and biological compositions. The extracellular matrix (ECM) of these musculoskeletal tissues interacts with cells to guide tissue formation. Since the ECM of such tissues is at the nanoscale, scaffolds in development are being developed which can mimic these structure. The structural features of the scaffolds affects cell adhesion, proliferation and differentiation. In order to repair musculoskeletal defects of bone, cartilage or tendon, synthetic materials are widely used. It is important that such materials must mimic the natural environment and provide an optimal matrix environment, biological properties including appropriate chemical cues such as growth factors and optimal mechanical properties to guide tissue regeneration. This chapter provides an overview of the properties of nanomaterials for bone, cartilage and tendon regeneration. It covers the aspects of incorporating nanoparticles with scaffolds to improve mechanical properties and the biocompatibility of polymers. The design, fabrication, challenges and success of incorporating of growth factors, genetic cues and drugs to enhance mechano-sentesive tissue has been provided with concluding remarkes on the future challenges and directions of nanomaterials for musculoskeletal tissues

Micropatterning of nanocomposite polymer scaffolds using sacrificial phosphate glass fibers for tendon tissue engineering applications

This study presents a simple and reproducible method of micro patterning the novel nanocomposite polymer (POSS-PCU) using a sacrificial phosphate glass fiber template for tendon tissue engineering applications. The diameters of the patterned scaffolds produced were dependent on the diameter of the glass fibers (15 μm) used. Scaffolds were tested for their physical properties and reproducibility using various microscopy techniques. For the first time, we show that POSS-PCU supports growth of human tenocytes cells. Furthermore, we show that cellular alignment, their biological function and expression of various tendon related proteins such as scleraxis, collagen I and III, tenascin-C are significantly elevated on the micro patterned polymer surfaces compared to flat samples. This study demonstrated a simple, reproducible method of micro patterning POSS-PCU nanocomposite polymer for novel tendon repair applications, which when provided with physical cues could help mimic the microenvironment of tenocytes cells

Applications of 3D printing in the management of severe spinal conditions

The latest and fastest-growing innovation in the medical field has been the advent of three-dimensional printing technol- ogies, which have recently seen applications in the production of low-cost, patient-specific medical implants. While a wide range of three-dimensional printing systems has been explored in manufacturing anatomical models and devices for the medical setting, their applications are cutting-edge in the field of spinal surgery. This review aims to provide a com- prehensive overview and classification of the current applications of three-dimensional printing technologies in spine care. Although three-dimensional printing technology has been widely used for the construction of patient-specific ana- tomical models of the spine and intraoperative guide templates to provide personalized surgical planning and increase pedicle screw placement accuracy, only few studies have been focused on the manufacturing of spinal implants. Therefore, three-dimensional printed custom-designed intervertebral fusion devices, artificial vertebral bodies and disc substitutes for total disc replacement, along with tissue engineering strategies focused on scaffold constructs for bone and cartilage regeneration, represent a set of promising applications towards the trend of individualized patient care

Evaluation of Sterilisation Techniques for Regenerative Medicine Scaffolds Fabricated with Polyurethane Nonbiodegradable and Bioabsorbable Nanocomposite Materials

An effective sterilisation technique that maintains structure integrity, mechanical properties, and biocompatibility is essential for the translation of new biomaterials to the clinical setting.We aimed to establish an effective sterilisation technique for a biodegradable (POSS-PCL) and nonbiodegradable (POSS-PCU) nanocomposite scaffold that maintains stem cell biocompatibility. Scaffolds were sterilised using 70% ethanol, ultraviolet radiation, bleach, antibiotic/antimycotic, ethylene oxide, gamma irradiation, argon plasma, or autoclaving. Samples were immersed in tryptone soya broth and thioglycollate medium and inspected for signs of microbial growth. Scaffold surface and mechanical and molecular weight properties were investigated. AlamarBlue viability assay of adipose derived stem cells (ADSC) seeded on scaffolds was performed to investigate metabolic activity. Confocal imaging of rhodamine phalloidin and DAPI stained ADSCs was performed to evaluate morphology. Ethylene oxide, gamma irradiation, argon plasma, autoclaving, 70% ethanol, and bleach were effective in sterilising the scaffolds. Autoclaving, gamma irradiation, and ethylene oxide led to a significant change in the molecular weight distribution of POSS-PCL and gamma irradiation and ethylene oxide to that of POSS-PCU (p<0.05). UV, ethanol, gamma irradiation, and ethylene oxide caused significant changes in the mechanical properties of POSS-PCL (p<0.05). Argon was associated with significantly higher surface wettability and ADSC metabolic activity (p<0.05). In this study, argon plasma was an effective sterilisation technique for both nonbiodegradable and biodegradable nanocomposite scaffolds. Argon plasma should be further investigated as a potential sterilisation technique for medical devices

Monte Carlo Study of Lipid Cholesterol Interactions in Biomembranes

Physic

Computational models for characterisation and design of patient-specific spinal implant

BACKGROUND CONTEXT: Spinal fusion is designed to reduce movements between vertebrae and therefore pain. The most used devices for this procedure are mainly made of titanium or polyether ether ketone (PEEK). However, the mismatch between devices, with standard shapes and materials, and the surrounding bones can lead to suboptimal outcomes. Computational models, namely, Finite Element Analyses (FEA), can be employed to optimise existing device and design more effective solutions. PURPOSE: The goal of this study was to compare the performance of different materials and material densities for spinal cages, and to design a novel geometry which can ideally match the anatomical characteristics of a patient. STUDY DESIGN/SETTING: Computational. PATIENT SAMPLE: Nil. OUTCOME MEASURES: Nil. METHODS: FEA were set up to simulate compression (400 N) and bending (7.5 Nm) on a generic cage design. Three materials were modelled: titanium, PEEK and polycarbonate. Polycarbonate was included as widely available within additive manufacturing techniques. For each of the cages, four designs were modelled with varying material filling density. Furthermore, a new cage was modelled to match the pre-operative computed tomography (CT) of a patient exactly. The patient-specific cage was also tested by means of FEA. RESULTS: Stress distribution was compared between all the three materials tested. Consistently, stresses increased with reducing material density. Stress peak values were lower than the respective risk of failure in all the simulated cases, confirming the feasibility of polycarbonate implants. The patient-specific design showed even stress distribution consistently within anatomical constraints. CONCLUSIONS: Computational analyses suggested the feasibility of a lighter, cheaper and patient-specific cage for spinal fusion

Feasibility of manufacturing a patient-specific spinal implant

Spinal fusion is performed for degenerative spinal condition when conservative measures fail. Implant size and shape are not standardised between manufacturers, and best match often means compromises. Bioprinting offers a unique opportunity to create a tailor-made solution. PURPOSE: The goal of this study was to design and manufacture a 3D-printed lumbar cage for lumbar interbody fusion

Development of a Tissue-Engineered Lymphatic Graft Using Nanocomposite Polymer for the Treatment of Secondary Lymphedema

Damage of the lymphatic vessels, commonly due to surgical resection for cancer treatment, leads to secondary lymphedema. Tissue engineering approach offers a possible solution to reconstruct this damage with the use of lymphatic graft to re-establish the lymphatic flow, hence preventing lymphedema. The aim of this study is to develop a tissue-engineered lymphatic graft using nanocomposite polymer and human dermal lymphatic endothelial cells (HDLECs). A nanocomposite polymer, the polyhedral oligomeric silsequioxane-poly(carbonate-urea)urethane (POSS-PCU), which has enhanced mechanical, chemical, and physical characteristics, was used to develop the lymphatic graft. POSS-PCU has been used clinically for the world's first synthetic trachea, lacrimal duct, and is currently undergoing clinical trial for coronary artery bypass graft. Two designs and fabrication methods were used to manufacture the conduits. The fabrication method, the mechanical and physical properties, as well as the hydraulic conductivity were tested. This is followed by in vitro cell culture analysis to test the cytocompatibility of HDLEC with the polymer surface. Using the casted extrusion method, the nanocomposite lymphatic graft demonstrates desirable mechanical property and hydraulic conductivity to re-establish the lymphatic flow. The conduit has high tensile strength (casted: 74.86 ± 5.74 MPa vs. coagulated: 31.33 ± 3.71 MPa; P < 0.001), favorable kink resistance, and excellent suture retention property (casted vs. coagulated, P < 0.05). Cytocompatibility study showed that the POSS-PCU scaffold supports the attachment and growth of HDLECs. This study demonstrates the feasibility of developing a tissue-engineered lymphatic graft using the nanocomposite polymer. It displays excellent mechanical property and cytocompatibility to HDLECs, offering much promise for clinical applications and as a new treatment option for secondary lymphedema