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Full Text, Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Dentistry&Oral Hlth, Griffith Health, Biomaterial scaffolds engineered to facilitate osteogenesis which can subsequently remodel in a similar fashion to that of natural tissue, is an ideal clinical strategy for treating bone defects in the maxillofacial region. This study has developed, using a novel melt electrowriting (MEW) technique, various graded porous polycaprolactone (PCL) scaffolds able to imitate the bimodal structure of cortical and cancellous bone tissue in terms of their morphological pore structure. These scaffolds were subsequently shown to facilitate the proliferation of osteoblasts with significant alkaline phosphatase (ALP) activity. Scaffolds with a staggered architecture i.e. those where the corresponding fibers in different layers are offset horizontally during the printing process, increases the number of contact points, enables larger pores, facilitates cell attachment and creates a highly porous structure with interconnected networks favourable for improved cell migration and vascularization. MEW is a relatively new technology that fills a gap between conventional fused deposition modelling (FDM) 3D printing and solution electrospinning by affording significantly better control over the fabrication of the porosity in scaffolds. This is due to the high-resolution during printing of the fibers which enables small pore sizes in the desired porosity. PCL polymer with its advantages of less immunoreactivity following implantation and mechanically suitability for the support of bone cells, has flexibility in design and is widely used in bone applications. However poor bioactivity and cellular affinity as well as long-term degradation issues with PCL have been reported. A promising solution to overcome these drawbacks is fiber surface modification such as coating with bioactive inorganic components. hydroxyapatite (HAP) is the most stable form of calcium phosphate (CaP) used to improve the hydrophobic characteristics of PCL and enhance the binding affinity to the host tissue and promote

Reconstructive surgery aims to restore tissue defects by replacing them with similar autologous tissue to achieve good clinical outcomes. However, often the defect is too large or the tissue available is limited, requiring synthetic materials to restore the anatomical shape and partial function. The utilization of three-dimensional (3D) printing allows for the manufacture of implants with complex geometries and internal architecture that more closely matches the required clinical needs. Synthetic polymers offer certain advantages over natural polymers as biomedical materials due to their ability to more closely mimic the mechanical and chemical properties of the native tissue. Synthetic polymer materials such as poly(lactic acid) and acrylonitrile butadiene styrene are easily 3D printed to generate 3D objects due to their flexibility in their chemical and mechanical properties and physical form. Polyurethanes (PUs) are widely used as short- and long-term, implantable medical devices due to their good mechanical properties, biocompatibility, and hemocompatibility. This article provides an overview on the advancement of 3D printable PU-based materials for biomedical applications. A summary of the chemical structure and synthesis of PUs is provided to explain how PUs may be processed into medical devices using additive manufacturing techniques. Currently, PUs are being explored by several 3D printing approaches, including fused filament fabrication, bioplotting, and stereolithography, to fabricate complex implants with precise patterns and shapes with fine resolution. PU scaffolds using 3D printing have shown good cell viability and tissue integration in vivo. The important limitations of PU printing are identified to stimulate future research. PUs offer a biocompatible, synthetic polymeric material that can be 3D printed to manufacture implants that are tailored to meet specific anatomical, mechanical, and biological requirements for biomedical applications.

Stereolithography (SL) has several advantages over traditional biomanufacturing techniques such as fused deposition modeling, including increased speed, accuracy, and efficiency. While SL has been broadly used in tissue engineering for the fabrication of three-dimensional scaffolds that can mimic the in vivo environment for cell growth and tissue regeneration, lithographic printing is usually performed on single-component materials cured with ultraviolet light, severely limiting the versatility and cytocompatibility of such systems. In this study, we report a highly tunable, low-cost photoinitiator system that we used to establish a systematic library of crosslinked materials based on low molecular weight poly(ethylene glycol) diacrylate. We assessed the physicochemical properties, photocrosslinking efficiency, cost performance, and biocompatibility to demonstrate the capability of manufacturing a multimaterial complex tissue scaffold. Color images are available online. Stereolithography (SL) has advantages over traditional biomanufacturing techniques, including accuracy and efficiency. While SL has been broadly used for fabricating three-dimensional scaffolds that can mimic the in vivo environment for cell growth and tissue regeneration, lithographic printing is usually performed on single-component materials cured with ultraviolet light, severely limiting the versatility and cytocompatibility of such systems. In this study, we report a highly tunable photoinitiator system and establish a systematic library of crosslinked materials based on poly(ethylene glycol) diacrylate. We assessed the physicochemical properties, photocrosslinking efficiency and biocompatibility to demonstrate the capability of manufacturing a multimaterial complex tissue scaffold.

Adipose tissue regeneration is an area of active research and greatly fueled by clinical needs. The reconstruction and augmentation of missing or diseased soft tissue has a long history and rich clinical success. Nonresorbable materials and autologous tissue transfer have been long established as common practice with good treatment outcomes. Yet recent advances have focused on the use of biodegradable materials, stem cells, and bioactive molecules to regenerate tissues with no or minimal usage of tissue flaps. This chapter will discuss recent progress in these areas focusing on breast tissue, which present a particular challenging problem of big volume regeneration after mastectomy.

Radiation therapy is a valuable option for treatment of skin cancer. In order to deliver the radiation dose to the superficial skin tumor, an X-ray source, electron beam radiation therapy or a radioisotope is applied. The effectiveness of these procedures is well established in the literature. Findings of some recent studies have indicated that beta particles can be of particular interest in suppressing skin tumor growth. Beta-emitting radioisotopes are favorable because of the short penetration depth of their emitted particles. Beta radiation can induce significant damage in superficial skin tumor, and at the same time, result in enhanced protection of the underlying healthy tissues. In this study, we propose the design of a patch that can be used in beta radiation therapy of skin cancer patients. For that, we describe the components of this radioactive patch, as well as a proposal for the subsequent clinical application procedure. A scaffold was used as a substrate for embedding the desired beta-emitting radioisotope, and two layers of hydrogel to provide protection and shielding for the radioactively labelled scaffold. The proposed design could provide a universal platform for all beta-emitting radioisotopes. Depending on the depth of the tumor spread, a suitable beta emitter for that specific tumor can be selected and used. This is of particular and critical importance in cases where the tumor is located directly on top of the bone and for which the depth of penetration of radiation should be limited to only the tumor volume. The proposed design has the mechanical flexibility to adapt to curved body regions so as to allow the use in anatomically challenging areas of the body.

Neurotechnology as a research area can be defined as the convergence of neuroscience and tissue engineering/regenerative medicine. Through directed global initiatives concentrated on a better understanding of the human brain, an exponential rise in innovative functional biomaterials for the symbiotic integration of man and machine has risen. Unfortunately, neurotechnology as with other disruptive technologies faces the daunting path of traversing the broad chasm between the bench (development of technology) and the bedside (application of technology). Clinical translation of medical devices intended to assess, monitor, and treat sensorimotor injuries must address a selection of design and functional constraints which are cost limiting from a traditional manufacturing perspective. As a highly versatile technology, 3D printing in combination with advanced functional materials can be used to manufacture scaffolds for tissue engineering the neural-prosthesis interface as well as devices with predesigned capabilities of integrating spatial and temporal data sets usable in a diagnostic and therapeutic context. Therefore, recent neurotechnological advancements will be discussed in the realm of 3D printed functional materials (>2013) with a focus on their potential for clinical translation.

We present a design rationale for stretchable soft network composites for engineering tissues that predominantly function under high tensile loads. The convergence of 3D-printed fibers selected from a design library and biodegradable interpenetrating polymer networks (IPNs) result in biomimetic tissue engineered constructs (bTECs) with fully tunable properties that can match specific tissue requirements. We present our technology platform using an exemplary soft network composite model that is characterized to be flexible, yet ∼125 times stronger (E = 3.19 MPa) and ∼100 times tougher (WExt = ∼2000 kJ m–3) than its hydrogel counterpart.

Three-dimensional (3D) functional constructs with biomimetic mechanical and chemical properties are ideal for various regenerative medicine applications. These properties of 3D fabricated constructs mainly depend on the intrinsic characteristics of the materials and fabrication method. In this respect, the current use of hydrogels for musculoskeletal tissue repair is not ideal due to the lack of suitable mechanical properties, as well as the high biomimetic requirement for success. To overcome this limitation, we developed a novel functionalized hydrogel with bioactive gold nanoparticles (GNPs), reinforcing a 3D printed microstructure via fused deposition modeling (FDM) for bone tissue regeneration. We used biodegradable thermoplastic polylactic acid (PLA) as the 3D printed microstructure in combination with photo-curable gelatin hydrogels as the encapsulation matrix for the incorporation of cyclic RGD conjugated GNPs (RGNP), and investigated their mechanical properties. In addition, human adipose-derived stem cells (ADSCs) were encapsulated within the gelatin hydrogel and examined for viability, morphology, and osteogenic differentiation in vitro. The results showed that the stiffness of the composite hydrogel on reinforcing a 3D printed microstructure can be readily modulated to simulate the stiffness of the human mandibular condyle. ADSCs encapsulated in the composite structures remained viable within the hydrogel and showed excellent spreading on the 3D printed PLA microstructure. More importantly, osteogenic differentiation with incorporated RGNPs promoted significantly higher gene expression of osteogenic specific factors. Therefore, reinforced composite hydrogels are suitable for stem cell differentiation control and bone tissue regeneration. This journal is © The Royal Society of Chemistry 2017.