3D printing PhycoTrix™ for wound healing

With the advent of additive manufacturing and its recent use in regenerative medicine, bioprinting has become a promising technology for tissue engineering applications. PhycoTrix™, a sulphated marine-derived polysaccharide, taken from the cell wall of a DNA barcoded green algal spp., (Chlorophyta), has a chemical structure similar to mammalian glycosaminoglycans found within the dermal skin layer extracellular matrix. This sustainable, under-utilised source of biomaterial was developed into a bioink for use in bioprinting. Specifically, a dual-network hydrogel was engineered through ionic and chemical means. This hydrogel was characterised following methacrylation through 1H NMR, FT-IR, and circular dichroism. The physical properties, printability, and crosslinking kinetics were all assessed through rheology and mechanical properties through micro-indentation. Preliminary cytocompatibility studies were evaluated using fibroblasts and adipose-derived stem cells. The results indicated relatively high cell binding affinity and proliferation compared to other alginate studies, suggesting this novel biomaterial could be useful for wound healing applications, such as wound dressings and matrices for tissue repair and regeneration

3D Printing StarPoreⓇ for Bone Tissue Engineering

Since the advent of Tissue Engineering (TE) in the late 1980’s, significant progress has been made within the biomedical landscape. A recently established branch within TE is biofabrication, a field that aims to automate the fabrication of biologically functional materials through the use of additive manufacturing or three-dimensional (3D) printing, among other techniques. Additive manufacturing offers fine control over part porosity, with the capacity to match the complex internal architecture of human bone. Coupled with clinical 3D scanning techniques, 3D printing has the capacity to generate implants that accurately match defected areas. However, due to the limited number of regulatory approved devices for human implantation and high cost of sophisticated powder bed fusion printers, the printing techniques are restricted. To be compatible with regulatory requirements, this work aims to utilise a widely accessible and regulatory approved device, high-density polyethylene (HDPE) to generate bone substitutes. HDPE in the form of StarPore® supplied by industry collaborator Anatomics Pty Ltd, a three-pronged star or trilobal shape, is an established material approved by both the Federal Drug Administration (FDA) in the United States of America and the Therapeutic Goods Administration (TGA) in Australia as a bone substitute for human implantation

Three-Dimensional Printing and Cell Therapy for Wound Repair

Significance: Skin tissue damage is a major challenge and a burden on healthcare systems, from burns and other trauma to diabetes and vascular disease. Although the biological complexities are relatively well understood, appropriate repair mechanisms are scarce. Three-dimensional bioprinting is a layer-based approach to regenerative medicine, whereby cells and cell-based materials can be dispensed in fine spatial arrangements to mimic native tissue. Recent Advances: Various bioprinting techniques have been employed in wound repair-based skin tissue engineering, from laser-induced forward transfer to extrusion-based methods, and with the investigation of the benefits and shortcomings of each, with emphasis on biological compatibility and cell proliferation, migration, and vitality. Critical issues: Development of appropriate biological inks and the vascularization of newly developed tissues remain a challenge within the field of skin tissue engineering. Future Directions: Progress within bioprinting requires close interactions between material scientists, tissue engineers, and clinicians. Microvascularization, integration of multiple cell types, and skin appendages will be essential for creation of complex skin tissue constructs

Development of rhamnose-rich hydrogels based on sulfated xylorhamno-uronic acid toward wound healing applications

An array of biological properties is demonstrated in the category of extracts broadly known as ulvans, including antibacterial, anti-inflammatory and anti-coagulant activities. However, the development of this category in biomedical applications is limited due to high structural variability across species and a lack of consistent and scalable sources. In addition, the modification and formulation of these molecules is still in its infancy with regard to progressing to product development. Here, a sulfated and rhamnose-rich, xylorhamno-uronic acid (XRU) extract from the cell wall of a controlled source of cultivated Australian ulvacean macroalgae resembles mammalian connective glycosaminoglycans. It is therefore a strong candidate for applications in wound healing and tissue regeneration. This study targets the development of polysaccharide modification for fabrication of 3D scaffolds for skin cell (fibroblast) culture. The XRU extract is methacrylated and UV-crosslinked to produce hydrogels with tuneable mechanical properties. The hydrogels demonstrate high cell viability and support cell proliferation over 14 days, which are far more functional than comparable alginate gels. Importantly, an XRU-based bioink is developed for extrusion printing 3D constructs both with and without cell encapsulation. These results highlight the close to product potential of this rhamnose-rich XRU extract as a promising biomaterial toward wound healing. Future studies should be focused on in-depth in vitro characterizations to examine the role of the material in dermal extracellular matrix (ECM) secretion of 3D printed structures, and in vivo characterizations to assess its capacity in supporting wound healing

Sulfated polysaccharide-based scaffolds for orthopaedic tissue engineering

Given their native-like biological properties, high growth factor retention capacity and porous nature, sulfated-polysaccharide-based scaffolds hold great promise for a number of tissue engineering applications. Specifically, as they mimic important properties of tissues such as bone and cartilage they are ideal for orthopaedic tissue engineering. Their biomimicry properties encompass important cell-binding motifs, native-like mechanical properties, designated sites for bone mineralisation and strong growth factor binding and signaling capacity. Even so, scientists in the field have just recently begun to utilise them as building blocks for tissue engineering scaffolds. Most of these efforts have so far been directed towards in vitro studies, and for these reasons the clinical gap is still substantial. With this review paper, we have tried to highlight some of the important chemical, physical and biological features of sulfated-polysaccharides in relation to their chondrogenic and osteogenic inducing capacity. Additionally, their usage in various in vivo model systems is discussed. The clinical studies reviewed herein paint a promising picture heralding a brave new world for orthopaedic tissue engineering

Fibrinogen, collagen, and transferrin adsorption to poly(3,4-ethylenedioxythiophene)-xylorhamno-uronic glycan composite conducting polymer biomaterials for wound healing applications

We present the conducting polymer poly (3,4-ethylenedioxythiophene) (PEDOT) doped with an algal-derived glycan extract, Phycotrix™ [xylorhamno-uronic glycan (XRU84)], as an innovative electrically conductive material capable of providing beneficial biological and electrical cues for the promotion of favorable wound healing processes. Increased loading of the algal XRU84 into PEDOT resulted in a reduced surface nanoroughness and interfacial surface area and an increased static water contact angle. PEDOT-XRU84 films demonstrated good electrical stability and charge storage capacity and a reduced impedance relative to the control gold electrode. A quartz crystal microbalance with dissipation monitoring study of protein adsorption (transferrin, fibrinogen, and collagen) showed that collagen adsorption increased significantly with increased XRU84 loading, while transferrin adsorption was significantly reduced. The viscoelastic properties of adsorbed protein, characterized using the ΔD/Δf ratio, showed that for transferrin and fibrinogen, a rigid, dehydrated layer was formed at low XRU84 loadings. Cell studies using human dermal fibroblasts demonstrated excellent cell viability, with fluorescent staining of the cell cytoskeleton illustrating all polymers to present excellent cell adhesion and spreading after 24 h

Laser Sintering Approaches for Bone Tissue Engineering

The adoption of additive manufacturing (AM) techniques into the medical space has revo-lutionised tissue engineering. Depending upon the tissue type, specific AM approaches are capable of closely matching the physical and biological tissue attributes, to guide tissue regeneration. For hard tissue such as bone, powder bed fusion (PBF) techniques have significant potential, as they are capable of fabricating materials that can match the mechanical requirements necessary to maintain bone functionality and support regeneration. This review focuses on the PBF techniques that utilize laser sintering for creating scaffolds for bone tissue engineering (BTE) applications. Optimal scaffold requirements are explained, ranging from material biocompatibility and bioactivity, to generating specific architectures to recapitulate the porosity, interconnectivity, and mechanical properties of native human bone. The main objective of the review is to outline the most common materials processed using PBF in the context of BTE; initially outlining the most common polymers, including polyamide, polycaprolactone, polyethylene, and polyetheretherketone. Subsequent sections investigate the use of metals and ceramics in similar systems for BTE applications. The last section explores how composite materials can be used. Within each material section, the benefits and shortcomings are outlined, including their mechanical and biological performance, as well as associated printing parameters. The framework provided can be applied to the development of new, novel materials or laser-based approaches to ultimately generate bone tissue analogues or for guiding bone regeneration

Additive manufacturing enables personalised porous high-density polyethylene surgical implant manufacturing with improved tissue and vascular ingrowth

Porous high-density polyethylene (pHDPE) surgical implants have played a significant role in aesthetic, reconstructive and skeletal augmentation procedures for more than 30 years and have been the gold-standard synthetic implant used in more than 400,000 procedures worldwide. The effects of pHDPE implant properties such as porosity, geometry and surface chemistry are crucial considerations. Additive manufacturing and plasma surface treatment are promising approaches to induce rapid tissue integration and vascularisation, improve healing times and lead to more satisfactory patient outcomes. Here, a novel pHDPE scaffold architecture obtained by laser sintering was characterised to quantify porosity variations as a result of manufacturing, compared to scaffolds manufactured via traditional moulding, laser sintering, and the clinical gold-standard surgical implant, MEDPORⓇ. Plasma surface treatment was also explored as a means of improving the hydrophilicity of the HDPE. An in vitro cell culture study examined the attachment of cells on treated and non-treated scaffolds. After 3 days, plasma-treated scaffolds exhibited a 1.6-fold increase in cell attachment compared to non-treated, hydrophobic samples. Plasma-treated and non-treated samples were then implanted subcutaneously in rats for 1, 4, and 8 weeks to assess biocompatibility, tissue ingrowth and vascularisation. Histological analysis revealed that laser sintered StarPoreⓇ scaffolds exhibited significantly higher tissue ingrowth compared to the moulded scaffolds, whilst fibrous encapsulation dominated the tissue response in moulded StarPoreⓇ scaffolds. Plasma treatment did not significantly affect the quantity of tissue ingrowth, however it significantly increased the density of blood vessels within sintered StarPoreⓇ scaffolds by an average of 86.6%. Overall, this study demonstrated that novel manufacturing and plasma treatment of pHDPE surgical implants enhanced cell attachment in vitro and increased blood vessel density in laser sintered StarPoreⓇ scaffolds in vivo.</p