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The article presents an in-depth discussion on the various additive manufacturing techniques such as binder jetting, directed-energy deposition, material extrusion, material jetting, powder-bed fusion, sheet lamination, and vat polymerization processes. This article then discusses the different critical material aspects of additively manufactured medical devices, beginning with the preprinting phase (material consistency and recycling), the printing phase (build orientation), and the postprinting phase (part evaluation, biocompatibility, and sterilization) with supporting materials.

Material jetting bioprinting is a highly promising three-dimensional (3D) bioprinting technique that facilitates drop-on-demand (DOD) deposition of biomaterials and cells at pre-defined positions with high precision and resolution. A major challenge that hinders the prevalent use of the material jetting bioprinting technique is due to its limited range of printable hydrogel-based bio-inks. As a proof-of-concept, further modifications were made to gelatin methacrylate (GelMA), a gold-standard bio-ink, to improve its printability in a thermal inkjet bioprinter (HP Inc. D300e Digital Dispenser). A two-step modification process comprising saponification and heat treatment was performed; the GelMA bio-ink was first modified

Material jetting bioprinting is a highly promising three-dimensional (3D) bioprinting technique that facilitates drop-on-demand (DOD) deposition of biomaterials and cells at pre-defined positions with high precision and resolution. A major challenge that hinders the prevalent use of the material jetting bioprinting technique is due to its limited range of printable hydrogel-based bio-inks. As a proof-of-concept, further modifications were made to gelatin methacrylate (GelMA), a gold-standard bio-ink, to improve its printability in a thermal inkjet bioprinter (HP Inc. D300e Digital Dispenser). A two-step modification process comprising saponification and heat treatment was performed; the GelMA bio-ink was first modified via a saponification process under highly alkali conditions to obtain saponified GelMA (SP-GelMA), followed by heat treatment via an autoclaving process to obtain heat-treated SP-GelMA (HSP-GelMA). The bio-ink modification process was optimized by evaluating the material properties of the GelMA bio-inks via rheological characterization, the bio-ink crosslinking test, nuclear magnetic resonance (NMR) spectroscopy and the material swelling ratio after different numbers of heat treatment cycles (0, 1, 2 and 3 cycles). Lastly, size-exclusion chromatography with multi-angle light scattering (SEC-MALS) was performed to determine the effect of heat treatment on the molecular weight of the bio-inks. In this work, the 4% H2SP-GelMA bio-inks (after 2 heat treatment cycles) demonstrated good printability and biocompatibility (in terms of cell viability and proliferation profile). Furthermore, thermal inkjet bioprinting of the modified hydrogel-based bio-ink (a two-step modification process comprising saponification and heat treatment) via direct/indirect cell patterning is a facile approach for potential fundamental cell-cell and cell-material interaction studies. Submitted/Accepted version This study was supported by the RIE2020 Industry Alignment Fund – Industry Collaboration Projects (IAF-ICP) Funding Initiative, as well as cash and in-kind contribution from the industry partner, HP Inc., through the HP-NTU Digital Manufacturing Corporate Lab.

Three-dimensional (3D) bioprinting systems serve as advanced manufacturing platform for the precise deposition of cells and biomaterials at pre-defined positions. Among the various bioprinting techniques, the drop-on-demand jetting approach facilitates deposition of pico/nanoliter droplets of cells and materials for study of cell-cell and cell-matrix interactions. Despite advances in the bioprinting systems, there is a poor understanding of how the viability of primary human cells within sub-nanoliter droplets is affected during the printing process. In this work, a thermal inkjet system is utilized to dispense sub-nanoliter cell-laden droplets, and two key factors - droplet impact velocity and droplet volume - are identified to have significant effect on the viability and proliferation of printed cells. An increase in the cell concentration results in slower impact velocity, which leads to higher viability of the printed cells and improves the printing outcome by mitigating droplet splashing. Furthermore, a minimum droplet volume of 20 nL per spot helps to mitigate evaporation-induced cell damage and maintain high viability of the printed cells within a printing duration of 2 min. Hence, controlling the droplet impact velocity and droplet volume in sub-nanoliter bioprinting is critical for viability and proliferation of printed human primary cells. Published version This study is supported under the RIE2020 Industry Alignment Fund – Industry Collaboration Projects (IAFICP) Funding Initiative, as well as cash and in-kind contribution from the industry partner, HP Inc., through the HP-NTU Digital Manufacturing Corporate Lab.

The global prevalence of respiratory diseases caused by infectious pathogens has resulted in an increased demand for realistic in-vitro alveolar lung models to serve as suitable disease models. This demand has resulted in the fabrication of numerous two-dimensional (2D) and three-dimensional (3D) in-vitro alveolar lung models. The ability to fabricate these 3D in-vitro alveolar lung models in an automated manner with high repeatability and reliability is important for potential scalableproduction. In this study, we reported the fabrication of human triple-layered alveolar lung models comprising of human lung epithelial cells, human endothelial cells, and human lung fibroblasts using the drop-on-demand (DOD) 3D bioprinting technique. The polyvinylpyrrolidone-based bio-inks and the use of a 300 μm nozzle diameter improved the repeatability of the bioprinting process by achieving consistent cell output over time using different human alveolar lung cells. The 3D bioprintedhuman triple-layered alveolar lung models were able to maintain cell viability with relative similar proliferation profile over time as compared to non-printed cells. This DOD 3D bioprinting platform offers an attractive tool for highly repeatable and scalable fabrication of 3D in-vitro human alveolar lung models.

As a proof-of-concept, a two-step bioprinting strategy is implemented to fabricate the 3D pigmented human skin constructs. The first step involves the development and optimization of a suitable polyvinylpyrrolidone (PVP)-based bio-ink for printing of cells with enhanced viability and homogeneity. The experimental results have highlighted the importance of bio-ink properties (represented by Z values) on printed cells; the printed cells that are cultured over a period of 96-hours do not show significant printing-induced damage when the Z values of the PVP-based bio-inks are below 9.30. This critical step facilitates the patterning of epidermal melanin units (EMUs, cell-cell interactions between the keratinocytes and melanocytes) at an optimal ratio and density. The second step involves the engineering the complex 3D microstructures in the collagen-fibroblast matrices using macromolecular crowding. An in-depth investigation is performed to first understand the synergistic effect of macromolecular crowding (MMC) on the complex 3D collagen-fibroblast matrices. The MMC can be used to alter the 3D microstructures (pore size and porosity) within the collagen-fibroblast matrices; the pore size of the 3D collagen-fibroblast matrices plays a critical role in regulating the cell-matrix remodeling process and cellular behavior. The study highlights the importance of hierarchical pore sizes within the 3D dermal skin constructs and provides critical insights (optimal pore size range for each region of the proposed tri-zone dermal constructs) for the development of improved dermal skin constructs using MMC. As such, a drop-on-demand bioprinting-based strategy is implemented to facilitate the precise deposition of PVP-based bio-ink at desired positions within each printed layer of collagen to manipulate the pore size within each printed region and eventually fabricate 3D hierarchical porous collagen-based structures. The 3D hierarchical porous collagen-fibroblast matrices serve as the dermal skin constructs for patterning of EMUs. Lastly, the feasibility of fabricating pigmented human skin constructs with uniform skin pigmentation (using 3 different skin cells from 3 different skin donors) is demonstrated. The histological analysis of the 3D bioprinted pigmented human skin constructs has revealed the similar morphological appearance to the native skin and the immunochemical analysis has indicated the presence of some important biomarkers in native skin. Although 3D bioprinting is an advanced manufacturing platform, it is critical to note that a holistic approach of combining bioprinting-based strategy with other important strategies such as MMC and co-culture techniques has facilitated the fabrication of 3D pigmented human skin constructs with uniform skin pigmentation. Doctor of Philosophy (MAE)

Bioelectronics platforms are gaining widespread attention as they provide a template to study the interactions between biological species and electronics. Decoding the effect of the electrical signals on the cells and tissues holds the promise for treating the malignant tissue growth, regenerating organs and engineering new-age medical devices. This work is a step forward in this direction, where bio- and electronic materials co-exist on one platform without any need for post processing. We fabricate a freestanding and flexible hydrogel based platform using 3D bioprinting. The fabrication process is simple, easy and provides a flexible route to print materials with preferred shapes, size and spatial orientation. Through the design of interdigitated electrodes and heating coil, the platform can be tailored to print various circuits for different functionalities. The biocompatibility of the printed platform is tested using C2C12 murine myoblasts cell line. Furthermore, normal human dermal fibroblasts (primary cells) are also seeded on the platform to ascertain the compatibility. NRF (Natl Research Foundation, S’pore)

The use of hydrogels enables the encapsulation and patterning of living cells within 3-D environment that closely mimic the physical, chemical, and biological aspects of the native extracellular matrix (ECM). This chapter first reviews the developments, key characteristics, and applications of some commonly used and emerging hydrogels. It then discusses the compatibility between hydrogels and the bioprinting processes and highlights some of the recent emerging trends in hydrogel research.

The editorial team greatly appreciates the reviewers who have dedicated their considerable time and expertise to the journal’s rigorous editorial process over the past 12 months, regardless of whether the papers are finally published or not [...]

Over the years, the field of bioprinting has attracted attention for its highly automated fabrication system that enables the precise patterning of living cells and biomaterials at pre-defined positions for enhanced cell-matrix and cell-cell interactions. Notably, vat polymerization (VP)-based bioprinting is an emerging bioprinting technique for various tissue engineering applications due to its high fabrication accuracy. Particularly, different photo-initiators (PIs) are utilized during the bioprinting process to facilitate the crosslinking mechanism for fabrication of high-resolution complex tissue constructs. The advancements in VP-based printing have led to a paradigm shift in fabrication of tissue constructs from cell-seeding of tissue scaffolds (non-biocompatible fabrication process) to direct bioprinting of cell-laden tissue constructs (biocompatible fabrication process). This paper, presenting a first-time comprehensive review of the VP-based bioprinting process, provides an in-depth analysis and comparison of the various biocompatible PIs and highlights the important considerations and bioprinting requirements. This review paper reports a detailed analysis of its printing process and the influence of light-based curing modality and PIs on living cells. Lastly, this review also highlights the significance of VP-based bioprinting, the regulatory challenges and presents future directions to transform the VP-based printing technology into imperative tools in the field of tissue engineering and regenerative medicine. The readers will be informed on the current limitations and achievements of the VP-based bioprinting techniques. Notably, the readers will realize the importance and value of highly-automated platforms for tissue engineering applications and be able to develop objective viewpoints towards this field. Accepted version

Over the years, the field of toxicology testing has evolved tremendously from the use of animal models to the adaptation of in vitro testing models. In this perspective article, we aim to bridge the gap between the regulatory authorities who performed the testing and approval of new chemicals and the scientists who designed and fabricated these in vitro testing models. An in-depth discussion of existing toxicology testing guidelines for skin tissue models (definition, testing models, principle, and limitations) is first presented to have a good understanding of the stringent requirements that are necessary during the testing process. Next, the ideal requirements of toxicology testing platform (in terms of fabrication, testing, and screening process) are discussed. We envisioned that the integration of three-dimensional bioprinting within miniaturized microfluidics platform would bring about a paradigm shift in the field of toxicology testing; providing standardization in the fabrication process, accurate and rapid deposition of test chemicals, real-time monitoring and high throughput screening for more efficient skin toxicology testing.

Bioprinting provides a fully automated and advanced platform that facilitates the simultaneous and highly specific deposition of multiple types of skin cells and biomaterials, a process that is lacking in conventional skin tissue-engineering approaches. Here, we provide a realistic, current overview of skin bioprinting, distinguishing facts from myths. We present an in-depth analysis of both current skin bioprinting works and the cellular and matrix components of native human skin. We also highlight current limitations and achievements, followed by design considerations and a future outlook for skin bioprinting. The potential of bioprinting with converging opportunities in biology, material, and computational design will eventually facilitate the fabrication of improved tissue-engineered (TE) skin constructs, making bioprinting skin an impending reality.

Collagen is the most abundant extracellular matrix protein that is widely used in tissue engineering (TE). There is little research done on printing pure collagen. To understand the bottlenecks in printing pure collagen, it is imperative to understand collagen from a bottom-up approach. Here it is aimed to provide a comprehensive overview of collagen printing, where collagen assembly in vivo and the various sources of collagen available for TE application are first understood. Next, the current printing technologies and strategy for printing collagen-based materials are highlighted. Considerations and key challenges faced in collagen printing are identified. Finally, the key research areas that would enhance the functionality of printed collagen are presented. Nanyang Technological University National Research Foundation (NRF) This research was supported by the National Research Foundation, Prime Minister’s Office, Singapore under its Medium-Sized Centre funding scheme. This work was also supported by NTU start-up grant. This research was conducted in collaboration with HP Inc. and supported/partially supported by the Singapore Government through the Industry Alignment Fund-Industry Collaboration Projects Grant.

One of the major challenges in the field of soft tissue engineering using bioprinting is fabricating complex tissue constructs with desired structure integrity and mechanical property. To accomplish such requirements, most of the reported works incorporated reinforcement materials such as poly(ϵ-caprolactone) (PCL) polymer within the 3D bioprinted constructs. Although this approach has made some progress in constructing soft tissue-engineered scaffolds, the mechanical compliance mismatch and long degradation period are not ideal for soft tissue engineering. Herein, we present a facile bioprinting strategy that combines the rapid extrusion-based bioprinting technique with an in-built ultraviolet (UV) curing system to facilitate the layer-by-layer UV curing of bioprinted photo-curable GelMA-based hydrogels to achieve soft yet stable cell-laden constructs with high aspect ratio for soft tissue engineering. GelMA is supplemented with a viscosity enhancer (gellan gum) to improve the bio-ink printability and shape fidelity while maintaining the biocompatibility before crosslinking via a layer-by-layer UV curing process. This approach could eventually fabricate soft tissue constructs with high aspect ratio (length to diameter) of ≥ 5. The effects of UV source on printing resolution and cell viability were also studied. As a proof-of-concept, small building units (3D lattice and tubular constructs) with high aspect ratio are fabricated. Furthermore, we have also demonstrated the ability to perform multi-material printing of tissue constructs with high aspect ratio along both the longitudinal and transverse directions for potential applications in tissue engineering of soft tissues. This layer-by-layer ultraviolet assisted extrusion-based (UAE) Bioprinting may provide a novel strategy to develop soft tissue constructs with desirable structure integrity. Published version

Bioprinting offers a highly-automated and advanced manufacturing platform that facilitates the deposition of bio-inks (living cells, biomaterials and growth factors) in a scalable and reproducible manner, a process that is lacking in conventional tissue engineering approaches. Significant improvements in the field of bioprinting have occurred over the last two decades. This reviews provides an in-depth analysis of recent improvements in the bioprinting techniques, progress in bio-ink development, implementation of new bioprinting and tissue maturation strategies. Special attention is givent to the role of polymer science and how it complements 3D bioprinting to overcome some of the major impediments in the field of organ printing. A concise overview of the anatomy and physiology of different tissues/organs is provided, followed by important design considerations to better facilitate the fabrication of biomimetic tissues/organs for tissue engineering and regenerative medicine (TERM). Last, a realistic overview of current status in organ bioprinting is presented, including recent accomplishments in bioprinting tissue-engineered constructs, the limitations and challenges, as well as opportunities for future research. We strongly believe that with the advances in polymer sciences, it will be an impending reality for on-demand bioprinting of patient-specific tissues/organs. Accepted version

Chronic wounds are the result of disruptions in the body's usual process of healing. They are not only a source of significant pain and discomfort but also, more importantly, an unguarded port of entry for pathogens into the body. While our current understanding of this phenomenon is far from complete, findings in physiological patterns and advancements in wound healing technologies have helped develop wound management and healing solutions to this long-standing medical challenge. This review presents an overview of known wound healing mechanics, abnormalities that lead to chronic wounds, and a summary of established and new wound healing technologies. Various approaches to heal wounds are discussed, from dermal replacements to advanced biomaterial-based treatments, from cell-, synthetic-, and composite-based approaches to preclinical approaches, which make developing such products possible. While tested breakthrough products are described, the authors focused more on recently developed innovations, which are at varying stages of maturity. The review concludes with a note on future perspectives and opinions on where the field and industry are headed and where they should be. Impact Statement Wound healing is an important area of research and clinical practice, and has captured the attention of tissue engineers since the nascent beginnings of the discipline. Tissue-engineered skin was the first FDA-approved product, achieved in 1996. Despite this success, and the passage of time, healing wounds, particularly chronic wounds, remains a vexing challenge. This comprehensive review article will provide readers with a synopsis of current issues, research approaches, animal models, technologies, and products that span the continuum from early development to clinical studies, in the hope of fueling new interests and ideas to overcome this long-standing medical challenge.

Bioprinting is an emerging technology that offers the unique ability to deposit and pattern different cells and matrix materials to fabricate three-dimensional (3-D) tissue constructs. Markedly, bioprinting demonstrated great potential for skin tissue engineering ranging from the development of 3-D skin tissue models to in-situ bioprinting of skin directly over the wound site. Nevertheless, one of the major challenges that impede the progress in this field is the limited choices of printable biomaterials. In this paper, we report the development of printable polyelectrolyte chitosan-gelatin hydrogel for potential applications in tissue engineering of skin. The oppositely charged functional groups from chitosan and gelatin respectively first interacted at a specific pH range to form a polyelectrolyte complex, followed by further pH-dependent crosslinking. The pH-crosslinked polyelectrolyte chitosan-gelatin hydrogel was then evaluated in terms of its rheological behavior, biocompatibility, printability and lastly material stability under physiological conditions. The polyelectrolyte chitosan-gelatin hydrogel remained in a robust gel-state over the temperature range of 20-40 o C and facilitated cellular attachment and proliferation. Furthermore, it demonstrated good printability and the multi-layered hydrogel construct was mechanically stable after subjecting it to physiological conditions for 7 days.

Three-dimensional (3D) pigmented human skin constructs have been fabricated using a 3D bioprinting approach. The 3D pigmented human skin constructs are obtained from using three different types of skin cells (keratinocytes, melanocytes and fibroblasts from three different skin donors) and they exhibit similar constitutive pigmentation (pale pigmentation) as the skin donors. A two-step drop-on-demand bioprinting strategy facilitates the deposition of cell droplets to emulate the epidermal melanin units (pre-defined patterning of keratinocytes and melanocytes at the desired positions) and manipulation of the microenvironment to fabricate 3D biomimetic hierarchical porous structures found in native skin tissue. The 3D bioprinted pigmented skin constructs are compared to the pigmented skin constructs fabricated by conventional a manual-casting approach; in-depth characterization of both the 3D pigmented skin constructs has indicated that the 3D bioprinted skin constructs have a higher degree of resemblance to native skin tissue in term of the presence of well-developed stratified epidermal layers and the presence of a continuous layer of basement membrane proteins as compared to the manually-cast samples. The 3D bioprinting approach facilitates the development of 3D in vitro pigmented human skin constructs for potential toxicology testing and fundamental cell biology research. ASTAR (Agency for Sci., Tech. and Research, S’pore)

Native tissues and/or organs possess complex hierarchical porous structures that confer highly-specific cellular functions. Despite advances in fabrication processes, it is still very challenging to emulate the hierarchical porous collagen architecture found in most native tissues. Hence, the ability to recreate such hierarchical porous structures would result in biomimetic tissue-engineered constructs. Here, a single-step drop-on-demand (DOD) bioprinting strategy is proposed to fabricate hierarchical porous collagen-based hydrogels. Printable macromolecule-based bio-inks (polyvinylpyrrolidone, PVP) have been developed and printed in a DOD manner to manipulate the porosity within the multi-layered collagen-based hydrogels by altering the collagen fibrillogenesis process. The experimental results have indicated that hierarchical porous collagen structures could be achieved by controlling the number of macromolecule-based bio-ink droplets printed on each printed collagen layer. This facile single-step bioprinting process could be useful for the structural design of collagen-based hydrogels for various tissue engineering applications. Accepted version

In 3D bioprinting, printing resolution represents the deposited material in the x- and y-axes, while dimensionality defines the structural resolution of printed constructs. Dimensionality in 3D bioprinting can be defined as the resolution in the z-axis. The printing resolution, together with dimensionality, contributes to the overall shape fidelity of the bioprinted constructs. The in-depth understanding of physical processes for different printing technologies is imperative in controlling the print resolution and definition. In this article, bioprinting technologies are classified according to the physical processes that deposit or form the bioprinted construct. Due to the different fabrication processes in forming fundamental printed units (voxels), the definition of printability differs for each bioprinting technique. Another aspect of resolution is the spatial positioning of cells within each fundamental building unit. The proximity of cells in the bioprinted construct affects the physiological outcomes. The second aspect of 3D bioprinting technologies is the ability to control shape fidelity. Different strategies have been used to improve the construction of a 3D engineered tissue or organ. Lastly, moving toward complex tissue printing involves adding functionalities to the bioprinted construct. Data processing, material formulations, and integration of different fabrication technologies are key areas in bioprinting that can recapture the different hierarchical aspects of native tissues. This article presents a comprehensive overview of enhancing the resolution of the bioprinting construct and identifying methods to improve functionalities of bioprinted tissues. NRF (Natl Research Foundation, S’pore) Published version

We report a compact opto-fluidic platform capable of continuous analyte loading and unloading with a 3 dB optical insertion loss. The customized opto-fluidic manipulator enabled infiltration of photonic crystal fibers (PCFs) at ten times the rate achievable by capillary action. Additionally, it is to our knowledge, the first demonstration of complete and rapid evacuation performed with a syringe pump for extended lengths (>100 mm) of PCF. These properties render the device highly promising for continuous real-time sensing applications. Study was conducted on a PCF under macro-bending, taking advantage of its wavelength-dependent bending losses that red-shifted with the increasing refractive indices of the infiltrated analytes. The flexibility of the platform also facilitated the selection of an optimal bending radius (12.5 mm) for the analysis, based on sensitivity (Δ λ /Δ n ) and signal to noise ratio ( Q -factor). The subsequent comparison of experiment with simulation results was noted to show good coherence. Moreover, experimental results showed repeatability throughout the multiple cycles of infiltration and evacuation executed. The further employment of the device in the chemical sensing of ethanol solutions exhibited good consistency with calibrated data for concentrations up to 50% by weight.

Bioprinting is an emerging research field that has attracted tremendous attention for various applications; it offers a highly automated, advanced manufacturing platform for the fabrication of complex bioengineered constructs. Different bio-inks comprising multiple types of printable biomaterials and cells are utilized during the bioprinting process to improve the homology to native tissues and/or organs in a highly reproducible manner. This paper, presenting a first-time comprehensive yet succinct review of microvalve-based bioprinting, provides an in-depth analysis and comparison of different drop-on-demand bioprinting systems and highlights the important considerations for microvalve-based bioprinting systems. This review paper reports a detailed analysis of its printing process, bio-ink properties and cellular components on the printing outcomes. Lastly, this review highlights the significance of drop-on-demand bioprinting for various applications such as high-throughput screening, fundamental cell biology research, in situ bioprinting and fabrication of in vitro tissue constructs and also presents future directions to transform the microvalve-based bioprinting technology into imperative tools for tissue engineering and regenerative medicine.

Drop-on-demand (DOD) bioprinting has attracted huge attention for numerous biological applications due to its precise control over material volume and deposition pattern in a contactless printing approach. 3D bioprinting is still an emerging field and more work is required to improve the viability and homogeneity of printed cells during the printing process. Here, a general purpose bio-ink was developed using polyvinylpyrrolidone (PVP) macromolecules. Different PVP-based bio-inks (0%–3% w/v) were prepared and evaluated for their printability; the short-term and long-term viability of the printed cells were first investigated. The Z value of a bio-ink determines its printability; it is the inverse of the Ohnesorge number (Oh), which is the ratio between the Reynolds number and a square root of the Weber number, and is independent of the bio-ink velocity. The viability of printed cells is dependent on the Z values of the bio-inks; the results indicated that the cells can be printed without any significant impairment using a bio-ink with a threshold Z value of ≤9.30 (2% and 2.5% w/v). Next, the cell output was evaluated over a period of 30 min. The results indicated that PVP molecules mitigate the cell adhesion and sedimentation during the printing process; the 2.5% w/v PVP bio-ink demonstrated the most consistent cell output over a period of 30 min. Hence, PVP macromolecules can play a critical role in improving the cell viability and homogeneity during the bioprinting process. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version

Bioprinting is a promising automated platform that enables the simultaneous deposition of multiple types of cells and biomaterials to fabricate complex three-dimensional (3D) tissue constructs. Most of the previous bioprinting works focused on collagen-based biomaterial, which has poor printability and long crosslinking time. This posed a immerse challenge to create a 3D construct with pre-determined shape and configuration. There is a need for a functional material with good printability in order to fabricate a 3D skin construct. Recently, the use of chitosan for wound healing applications has attracted huge attention due to its attractive traits such as its antimicrobial properties and ability to trigger hemostasis. In this paper, we report the modification of chitosan-based biomaterials for functional 3D bioprinting. Modification to the chitosan was carried out via the oppositely charged functional groups from chitosan and gelatin at a specific pH of ~pH 6.5 to form polyelectrolyte complexes. The polyelectrolyte hydrogels were evaluated in terms of chemical interactions within polymer blend, rheological properties (viscosities, storage and loss modulus), printing resolution at varying pressures and feed rates and biocompatibility. The chitosan-based hydrogels formulated in this work exhibited good printability at room temperature, high shape fidelity of the printed 3D constructs and good biocompatibility with fibroblast skin cells.

The human skin is a complex organ consisting of multiple skin cells that work together to complement each other and provide essential functions such as skin barrier function, skin homeostasis and protection against the harmful ultraviolet radiation. Understanding the roles and paracrine signaling of different skin cells plus the influence of external stimuli on them are crucial towards the design of tissue-engineered skin constructs as these factors regulate the cellular behavior such as cell proliferation, migration and differentiation. Hence, an in-depth understanding of the knowledge on the epithelial-mesenchymal interactions would be valuable towards the design of a tissue-engineered skin construct.

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Key roles of the healthy human skin are to prevent bacterial infection and excessive loss of water. However, such essential roles are compromised in patients with severe burns or chronic wounds. Synthetic materials such as petrolatum gauze backings and silicone membranes are commonly used in wound dressings to improve its mechanical properties and temporarily restore the role of the damaged skin. These synthetic materials are usually non-biodegradable and subsequent removal of such temporary wound dressings from the wound site is necessary. This necessitates the development of biodegradable films for skin tissue engineering. Although solvent casting is a simple fabrication technique for such films, properties such as mechanical strength and water transmission rate cannot be easily controlled via solvent casting technique. In this paper, a bioprinting approach will be explored for the fabrication of films for skin wound healing. The potential of such bioprinted films for skin tissue engineering is highlighted. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version

Multi-layered liposomes, comprising a concentric series of lipid bilayers - separated at fixed distances and compartmentalizing aqueous solutions of alternating refractive indices - are proposed as optical Bragg resonators. Seminal work focuses on the feasibility of successive encapsulations coupled with size-control via extrusion. Synthesis criteria for realization of these liposomes were subsequently discussed based on experimental observations. Numerical studies of the proposed structure showed discernible band gaps, qualifying their potential application in biological lasing. Published version

A lab-in-fiber platform, comprising a photonic crystal fiber component for light-sample interaction, was experimentally demonstrated to be effective as a sensor and micro-reactor. Specifically, it enabled the discrimination between free and liposome-encapsulated fluorophores as well as allowed for the excitation of in-fiber plasmonic photothermal effects, by alternating between different fiber-coupled inputs. The significant increase in fluorescence emissions upon release of fluorophores, encapsulated within liposomes at self-quenching concentrations, was perceived as a shoulder in the device’s spectral output that otherwise only comprises the input excitation. Markedly, the observed shoulder was only discernible when the photonic crystal fiber was placed in a bent orientation. This was explained to be associated with the bending-induced refractive index profile changes in the fiber cross section that led to increased amounts of evanescent fields for light-sample interactions. Results highlighted the viability of the lab-in-fiber platform as an alternative to current lab-on-a-chip devices. Published version