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

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

Argon plasma modified nanocomposite polyurethane scaffolds provide an alternative strategy for cartilage tissue engineering

BACKGROUND: Children born with a small or absent ear undergo surgical reconstruction to create a suitable replacement using rib cartilage. To overcome the donor site morbidity and long-term pain of harvesting rib cartilage, synthetic materials can be a useful alternative. Medpor, is the currently used synthetic polyethylene material to replace missing facial cartilage but unfortunately it has high levels of surgical complications including infection and extrusion, making it an unsuitable replacement. New materials for facial cartilage reconstruction are required to improve the outcomes of surgical reconstruction. This study has developed a new nanomaterial with argon surface modification for auricular cartilage replacement to overcome the complications with Medpor. RESULTS: Polyurethanes nanocomposites scaffolds (PU) were modified with argon plasma surface modification (Ar) and compared to Medpor in vitro and in vivo. Ar scaffolds allowed for greater protein adsorption than Medpor and PU after 48 h (p < 0.05). Cell viability and DNA assays demonstrated over 14-days greater human dermal fibroblast adhesion and cell growth on Ar than PU and Medpor nanocomposites scaffolds (p < 0.05). Gene expression using RT-qPCR of collagen-I, fibronectin, elastin, and laminin was upregulated on Ar scaffolds compared to Medpor and PU after 14-days (p < 0.05). Medpor, unmodified polyurethane and plasma modified polyurethane scaffolds were subcutaneously implanted in the dorsum of mice for 12 weeks to assess tissue integration and angiogenesis. Subcutaneous implantation of Ar scaffolds in mice dorsum, demonstrated significantly greater tissue integration by H&E and Massons trichrome staining, as well as angiogenesis by CD31 vessel immunohistochemistry staining over 12-weeks (p < 0.05). CONCLUSIONS: Argon modified polyurethane nanocomposite scaffolds support cell attachment and growth, tissue integration and angiogenesis and are a promising alternative for facial cartilage replacement. This study demonstrates polyurethane nanocomposite scaffolds with argon surface modification are a promising biomaterial for cartilage tissue engineering applications

Pharmacognostic and Phytochemical Investigation of Ficus carica Linn.

Ficus carica Linn. (Syn: Ficus sycomorous; family: Moraceae) is grows in tropical and subtropical regions of India, used for varity of purpose in traditional medicine. The usefulness of this plant is scientifically evidenced, and different biologically active phytoconstituents were isolated form plant. But no reports are available on morphoanatomy, and phytochemical studies, hence present attempt was undertaken to investigate the microscopical and preliminary phytochemical studies. The study revels the midrib is biconvex and lamina is dorsiventral, shows presence of nonglandular trichome, anomocytic stomata, prismatic calcium oxalate crystals. It shows presence of steroids, triterpenoids, cumarines, flavanoids and glycoside

An update on the Application of Nanotechnology in Bone Tissue Engineering

BACKGROUND: Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation. METHODS: This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles. RESULTS: Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells. CONCLUSION: Future studies to improve the application of nanomaterials for bone tissue engineering are needed

Design and fabrication of 3D-printed anatomically shaped lumbar cage for intervertebra disc (IVD) degeneration treatment

Spinal fusion is the gold standard surgical procedure for degenerative spinal conditions when conservative therapies have been unsuccessful in rehabilitation of patients. Novel strategies are required to improve biocompatibility and osseointegration of traditionally used materials for lumbar cages. Furthermore, new design and technologies are needed to bridge the gap due to the shortage of optimal implant sizes to fill the intervertebral disc defect. Within this context, additive manufacturing technology presents an excellent opportunity to fabricate ergonomic shape medical implants. The goal of this study is to design and manufacture a 3D-printed lumbar cage for lumbar interbody fusion. Optimisations of the proposed implant design and its printing parameters were achieved via in silico analysis. The final construct was characterised via scanning electron microscopy, contact angle, x-ray micro computed tomography (μCT), atomic force microscopy, and compressive test. Preliminary in vitro cell culture tests such as morphological assessment and metabolic activities were performed to access biocompatibility of 3D-printed constructs. Results of in silico analysis provided a useful platform to test preliminary cage design and to find an optimal value of filling density for 3D printing process. Surface characterisation confirmed a uniform coating of nHAp with nanoscale topography. Mechanical evaluation showed mechanical properties of final cage design similar to that of trabecular bone. Preliminary cell culture results showed promising results in terms of cell growth and activity confirming biocompatibility of constructs. Thus for the first time, design optimisation based on computational and experimental analysis combined with the 3D-printing technique for intervertebral fusion cage has been reported in a single study. 3D-printing is a promising technique for medical applications and this study paves the way for future development of customised implants in spinal surgical applications

Neck Collar Assessment for People Living With Motor Neuron Disease: Are Current Outcome Measures Suitable?

A majority of people living with motor neuron disease (MND) experience weakness of the neck and as a result, experience head drop. This exacerbates problems with everyday activities (eating, talking, breathing, etc). Neck collars are often used to support head drop; however, these are typically designed for prehospitalization settings to manage and brace the cervical region of the spine. As a result, it has been recorded that people living with MND often reject these collars for a variety of reasons but most notably because they are too restricting. The current standardized outcome measures (most notably restricting cervical range of motion) used for neck collars are summarized herein along with whether they are suitable for a bespoke neck collar specifically designed for people living with MND

The biological context of HIV-1 host interactions reveals subtle insights into a system hijack

<p>Abstract</p> <p>Background</p> <p>In order to replicate, HIV, like all viruses, needs to invade a host cell and hijack it for its own use, a process that involves multiple protein interactions between virus and host. The HIV-1, Human Protein Interaction Database available at NCBI's website captures this information from the primary literature, containing over 2,500 unique interactions. We investigate the general properties and biological context of these interactions and, thus, explore the molecular specificity of the HIV-host perturbation. In particular, we investigate (i) whether HIV preferentially interacts with highly connected and 'central' proteins, (ii) known phenotypic properties of host proteins inferred from essentiality and disease-association data, and (iii) biological context (molecular function, processes and location) of the host proteins to identify attributes most strongly associated with specific HIV interactions.</p> <p>Results</p> <p>After correcting for ascertainment bias in the literature, we demonstrate a significantly greater propensity for HIV to interact with highly connected and central host proteins. Unexpectedly, we find there are no associations between HIV interaction and inferred essentiality. Similarly, we find a tendency for HIV not to interact with proteins encoded by genes associated with disease. Crucially, we find that functional categories over-represented in HIV-host interactions are innately enriched for highly connected and central proteins in the host system.</p> <p>Conclusions</p> <p>Our results imply that HIV's propensity to interact with highly connected and central proteins is a consequence of interactions with particular cellular functions, rather than being a direct effect of network topological properties. The lack of a propensity for interactions with phenotypically essential proteins suggests a selective pressure to minimise virulence in retroviral evolution. Thus, the specificity of HIV-host interactions is complex, and only superficially explained by network properties.</p

Application of high resolution DLP stereolithography for fabrication of tricalcium phosphate scaffolds for bone regeneration

Bone regeneration requires porous and mechanically stable scaffolds to support tissue integration and angiogenesis, which is essential for bone tissue regeneration. With the advent of additive manufacturing process, production of complex porous architecture has become feasible. However, a balance has to be sorted between porous architecture and mechanical stability which facilitates bone regeneration for load bearing applications. &amp;#13; Current study evaluates used of high resolution digital light processing (DLP) -based additive manufacturing to produce complex but mechanical stable scaffolds based on β-tricalcium phosphate (β-TCP) for bone regeneration. &amp;#13; Four different geometries, a rectilinear Grid, hexagonal Kagome, schwart primitive and hollow Schwarz are designed with 400 µm pores and 75 or 50 vol.% porosity. However after initial screening for design stability and mechanical properties, only a rectilinear Grid structure, a hexagonal Kagome structure are found to be reproducible and showed higher mechanical properties. &amp;#13; Micro computed tomography (µ-CT) analysis shows &amp;lt; 2 vol.% error in porosity and &amp;lt; 6 % relative deviation of average pore sizes for the Grid structures. At 50 vol.% porosity, this architecture also has the highest compressive strength of 44.7 MPa (Weibull modulus is 5.28), while bulk specimens reach 235 ± 37 MPa. &amp;#13; To evaluate suitability of 3D scaffolds produce by DLP methods for bone regeneration, scaffolds were cultured with murine preosteoblastic MC3T3-E1 cells. Short term study showed cells growth over 14 days, with more than two-fold increase of alkaline phosphatase (ALP) activity compared to cells on 2D tissue culture plastic. Collagen deposition was increased by a factor of 1.5 – 2 when compared to the 2D controls. This confirm retention of biocompatible and osteo-inductive properties of β-TCP following DLP process. &amp;#13; This study has implications for designing of the high resolution porous scaffolds for bone regenerative applications and contributes to understanding of DLP based additive manufacturing process for medical applications

Recent Developments and Characterization Techniques in 3D printing of Corneal Stroma Tissue

Corneal stroma has a significant function in normal visual function. The corneal stroma is vulnerable because of being the thickest part of the cornea, as it can be affected easily by infections or injuries. Any problems on corneal stroma can result in blindness. Donor shortage for corneal transplantation is one of the main issues in corneal transplantation. To address this issue, the corneal tissue engineering focuses on replacing injured tissues and repairing normal functions. Currently, there are no available, engineered corneal tissues for widely accepted routine clinical treatment, but new emerging 3D printing applications are being recognized as a promising option. Recent in vitro researches revealed that the biocompatibility and regeneration possessions of 3D-printed hydrogels outperformed conventional tissue engineering approaches. The goal of this review is to highlight the current developments in the characterization of 3D cell-free and bioprinted hydrogels