Christian Wiraja

Nanyang Technological University

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Chenjie Xu

City University of Hong Kong

David Yeo

St George Hospital

Mengjia Zheng

Zhangzhou Municipal Hospital of Fujian Province

Daniel Chin Shiuan Lio

Nanyang Technological University

Xiaoyu Ning

Shanghai Power Equipment Research Institute

Mingyue Cui

Zhengzhou University

Hao Chang

Chinese Academy of Sciences

Kanyi Pu

Nanyang Technological University

Sharon W. T. Chew

Nanyang Technological University

Jangsun Hwang

Korea University

Cooperative Institutions

Nanyang Technological University

National University of Singapore

Chinese Academy of Sciences

Agency for Science, Technology and Research

Duke-NUS Medical School

University of Chinese Academy of Sciences

Harvard University

University of Sydney

National Skin Centre

City University of Hong Kong

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Hydrogel-Based Technologies for the Diagnosis of Skin Pathology

Technologies (2020)

Christian Wiraja Xiaoyu Ning Mingyue Cui Chenjie Xu

Hydrogels, swellable hydrophilic polymer networks fabricated through chemical cross-linking or physical entanglement are increasingly utilized in various biomedical applications over the past few decades. Hydrogel-based microparticles, dressings and microneedle patches have been explored to achieve safe, sustained and on-demand therapeutic purposes toward numerous skin pathologies, through incorporation of stimuli-responsive moieties and therapeutic agents. More recently, these platforms are expanded to fulfill the diagnostic and monitoring role. Herein, the development of hydrogel technology to achieve diagnosis and monitoring of pathological skin conditions are highlighted, with proteins, nucleic acids, metabolites, and reactive species employed as target biomarkers, among others. The scope of this review includes the characteristics of hydrogel materials, its fabrication procedures, examples of diagnostic studies, as well as discussion pertaining clinical translation of hydrogel systems.

Scope (computer science)

10.3390/technologies8030047

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Citations (9)

Antibacterial performance of graphene oxide complemented with pluronic F-127 on physiologically mature gram-negative bacteria

H. Enis Karahan Christian Wiraja N. Farahin Binte Nasrun Silvana H. J. Toh Min Hao Goh

In a recent study, we have shown that the mixtures of graphene oxide (GO) nanosheets and Pluronic F-127 (PLU) polymers (GO-PLU) exhibit superior antimicrobial activity compared to GO alone on physiologically naïve bacteria challenged with hypoosmotic stress, particularly on Gram-negative species. Further, we have more recently demonstrated that the antibacterial activity of GO (alone) is significantly lower against physiologically mature bacteria. As inhibiting mature pathogens is important for practical biomedical applications, in this work, we studied the antibacterial performance of GO-PLU nanodispersions on mature Pseudomonas aeruginosa (P. aeruginosa) harvested at stationary phase. Colony counting and turbidimetric results showed that the antibacterial behavior of GO-PLU mixtures on mature bacteria displays a complex behavior showing dependence on both the environmental salinity and PLU concentration. At high osmolarity (i.e. low osmotic drop), PLU acts merely as an osmoprotectant rather than a synergistic killing agent in a concentration-dependent manner. At a higher level of osmotic drop, lower concentrations of PLU make almost no or a slight improvement in the antibacterial activity of GO, suggesting a competition in between the counteracting factors. Further tests using Escherichia coli (E. coli) have shown that the effect of GO-PLU on stationary-phase bacteria is also species(/strain)-specific. We expect these observations to pave the way for designing GO-based broad-spectrum disinfectant formulations, with the aid of suitable polymeric stabilizers. Given the high molecular weight polymers exist naturally in the ecological niches, the insights gained by current findings may also help to better understand the environmental fate of nanocarbons.

Osmotic concentration

Gram-Negative Bacteria

Disinfectant

Osmotic pressure

10.1109/nano.2017.8117478

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Citations (0)

Layer-by-Layer 3D Constructs of Fibroblasts in Hydrogel for Examining Transdermal Penetration Capability of Nanoparticles

SLAS TECHNOLOGY (2016)

Xiaochun Hou Shiying Liu Min Wang Christian Wiraja Wei Huang

Nanoparticles are emerging transdermal delivery systems. Their size and surface properties determine their efficacy and efficiency to penetrate through the skin layers. This work utilizes three-dimensional (3D) bioprinting technology to generate a simplified artificial skin model to rapidly screen nanoparticles for their transdermal penetration ability. Specifically, this model is built through layer-by-layer alternate printing of blank collagen hydrogel and fibroblasts. Through controlling valve on-time, the spacing between printing lines could be accurately tuned, which could enable modulation of cell infiltration in the future. To confirm the effectiveness of this platform, a 3D construct with one layer of fibroblasts sandwiched between two layers of collagen hydrogel is used to screen silica nanoparticles with different surface charges for their penetration ability, with positively charged nanoparticles demonstrating deeper penetration, consistent with the observation from an existing study involving living skin tissue.

Penetration (warfare)

Dermal fibroblast

10.1177/2211068216655753

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Citations (34)

Nitric Oxide Nanosensors for Predicting the Development of Osteoarthritis in Rat Model

ACS Applied Materials & Interfaces (2017)

Pan Jin Christian Wiraja Jinmin Zhao Jinlu Zhang Li Zheng

Osteoarthritis (OA) is a chronic arthritic disease that causes the overproduction of inflammatory factors such as nitric oxide (NO). This study develops a NO nanosensor to predict the OA development. The nanosensor is synthesized by encapsulating the NO sensing molecules (i.e., 4-amino-5-methylamino-2',7'-difluorofluorescein Diaminofluorescein-FM (DAF-FM)) within the biodegradable poly(lactic-co-glycolic acid) nanoparticles. In vitro, the nanosensor allows the monitoring of the NO release in interleukin-1β-stimulated chondrocytes and the alleviated effect of NG-monomethyl-l-arginine (a NO inhibitor) and andrographolide (an anti-inflammatory agent). In the rat OA model, it permits the quantification of NO level in joint fluid. The proposed NO nanosensor may facilitate a noninvasive and real-time evaluation of the OA development.

Nanosensor

Andrographolide

10.1021/acsami.7b06404

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Citations (54)

Recent Progress in Skin‐on‐a‐Chip Platforms

Advanced Therapeutics (2021)

Mingyue Cui Christian Wiraja Mengjia Zheng Gurvinder Singh Ken‐Tye Yong

Abstract As the largest organ of the body, the skin acts as a physical barrier for preventing excessive water loss and infection, and the host of many cosmetic and pharmaceutical products. Currently, two‐dimensional (2D) cell culture and animal models are extensively used as mainstream platforms to understand skin biology and assess therapeutic drug efficacy. However, 2D cell culture model fails to recapitulate the intricate interactions between cells and the extracellular matrix. The metabolic state of 2D‐cultured cells is typically similar, unlike the physiological condition in the body. Also, there is a growing ethical concern over the use of animal studies. Significant advances in microfluidics and tissue engineering have led to the development of three‐dimensional (3D) skin‐on‐a‐chip (SOC) technology, which offers a cost‐effective alternative to conventional preclinical models for the validation and testing of pharmaceutical and cosmetic products. This review discusses the recent developments in the design of various SOCs, their fabrication strategies and methods for introducing skill cells to the chip, and their respective biomedical applications. Finally, an outlook on current applications, challenges, and future research direction in this field is provided.

Organ-on-a-Chip

10.1002/adtp.202100138

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Citations (7)

Interference-free Micro/nanoparticle Cell Engineering by Use of High-Throughput Microfluidic Separation

ACS Applied Materials & Interfaces (2015)

David Yeo Christian Wiraja Yingying Zhou Hui Min Tay Chenjie Xu

Engineering cells with active-ingredient-loaded micro/nanoparticles is becoming increasingly popular for imaging and therapeutic applications. A critical yet inadequately addressed issue during its implementation concerns the significant number of particles that remain unbound following the engineering process, which inadvertently generate signals and impart transformative effects onto neighboring nontarget cells. Here we demonstrate that those unbound micro/nanoparticles remaining in solution can be efficiently separated from the particle-labeled cells by implementing a fast, continuous, and high-throughput Dean flow fractionation (DFF) microfluidic device. As proof-of-concept, we applied the DFF microfluidic device for buffer exchange to sort labeled suspension cells (THP-1) from unbound fluorescent dye and dye-loaded micro/nanoparticles. Compared to conventional centrifugation, the depletion efficiency of free dyes or particles was improved 20-fold and the mislabeling of nontarget bystander cells by free particles was minimized. The microfluidic device was adapted to further accommodate heterogeneous-sized mesenchymal stem cells (MSCs). Complete removal of unbound nanoparticles using DFF led to the usage of engineered MSCs without exerting off-target transformative effects on the functional properties of neighboring endothelial cells. Apart from its effectiveness in removing free particles, this strategy is also efficient and scalable. It could continuously process cell solutions with concentrations up to 10(7) cells·mL(-1) (cell densities commonly encountered during cell therapy) without observable loss of performance. Successful implementation of this technology is expected to pave the way for interference-free clinical application of micro/nanoparticle engineered cells.

Separation (statistics)

10.1021/acsami.5b06167

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Citations (25)

Peptide delivery with poly(ethylene glycol) diacrylate microneedles through swelling effect

Bioengineering & Translational Medicine (2017)

Shiying Liu David Yeo Christian Wiraja Hong Liang Tey Milan Mrksich

Abstract Transdermal delivery of therapeutic biomolecules (including peptides) can avoid enzymatic digestion that occurs in the oral route. (Polyethylene glycol) diacrylate (PEGDA)‐based microneedles, with good biocompatibility, are easily fabricated through photo‐polymerization with a precisely controlled structure. It has successfully been used for the transdermal delivery of small molecule drugs such as 5‐fluorouracil. However, the delivery of peptide‐based therapeutics using this platform is seldom reported. This is because of the potential damage to the peptide during the photo‐polymerization process of PEGDA. Herein, we introduce a method to load PEGDA microneedles with peptides without compromising peptide potency. Using gap junction inhibitor (Gap 26) as an example, the peptide was loaded into PEGDA microneedles through the swelling effect of PEGDA in the aqueous solution. The peptide‐loaded microneedles were applied to a keloid scar model and exhibited inhibition expression of collagen I, a predominant marker of keloid scar, demonstrating its potential therapeutic effects.

Biocompatibility

Biomolecule

PEGylation

10.1002/btm2.10070

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Citations (64)

Smart Magnetic Nanosensors Synthesized through Layer-by-Layer Deposition of Molecular Beacons for Noninvasive and Longitudinal Monitoring of Cellular mRNA

ACS Applied Materials & Interfaces (2016)

Min Wang Xiaochun Hou Christian Wiraja Libo Sun Zhichuan J. Xu

Noninvasive and longitudinal monitoring of gene expression in living cells is essential for understanding and monitoring cellular activities. Herein, a smart magnetic nanosensor is constructed for the real-time, noninvasive, and longitudinal monitoring of cellular mRNA expression through the layer-by-layer deposition of molecular beacons (MBs) and polyethylenimine on the iron oxide nanoparticles. The loading of MBs, responsible for the signal intensity and the tracking time, was easily tuned with the number of layers incorporated. The idea was first demonstrated with the magnetic nanosensors for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, which was efficiently internalized into the cells under the influence of magnetic field. This nanosensor allowed the continuous monitoring of the cellular GAPDH mRNA expression for 1 month. Then this platform was further utilized to incorporate two kinds of MBs for alkaline phosphatase (ALP) and GAPDH mRNAs, respectively. The multifunctional nanosensors permitted the simultaneous monitoring of the reference gene (GAPDH mRNA) and the early osteogenic differentiation marker (ALP mRNA) expression. When the fluorescence signal ratio between ALP mRNA MBs and GAPDH mRNA MBs was taken, the dynamic osteogenic differentiation process of MSCs was accurately monitored.

Nanosensor

Glyceraldehyde 3-phosphate dehydrogenase

Molecular beacon

10.1021/acsami.5b12234

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Citations (23)

Transdermal delivery of Chinese herbal medicine extract using dissolvable microneedles for hypertrophic scar treatment

Acta Pharmaceutica Sinica B (2021)

Xiaoyu Ning Christian Wiraja Sharon W. T. Chew Chen Fan Chenjie Xu

Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition. Although systemic treatments exist in clinic to manage hypertrophic scars, they pose significant side effects and tend to lose efficacy over prolonged applications. Traditional Chinese medicine (TCM) offers as a promising candidate to treat pathological scars. A large number of TCMs have been studied to show anti-scarring effect, however, the natural barrier of the skin impedes their penetration, lowering its therapeutic efficacy. Herein, we reported the use of dissolvable hyaluronic acid (HA) microneedles (MNs) as a vehicle to aid the transdermal delivery of therapeutic agent, a model TCM called shikonin for the treatment of hypertrophic scars. Here, shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration, making its dosage controllable during the fabrication process. The therapeutic effect of the shikonin HA MNs was studied in vitro using HSFs and then further verified with quantitative reverse transcriptase polymerase chain reaction. Our data suggest that the shikonin HA MNs significantly reduce the viability and proliferation of the HSFs and downregulate the fibrotic-related genes (i.e., TGFβ1, FAP-α and COL1A1). Furthermore, we observed a localized therapeutic effect of the shikonin HA MNs that is beneficial for site-specific treatment.

Therapeutic effect

Hypertrophic scars

Penetration (warfare)

Regenerative Medicine

10.1016/j.apsb.2021.03.016

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Citations (62)

Nanodelivery Systems for Topical Management of Skin Disorders

Molecular Pharmaceutics (2020)

Mingyue Cui Christian Wiraja Sharon Wan Ting Chew Chenjie Xu

Topical drug delivery has inherent advantages over other administration routes. However, the existence of stratum corneum limits the diffusion to small and lipophilic drugs. Fortunately, the advancement of nanotechnology brings along opportunities to address this challenge. Taking the unique features in size and surface chemistry, nanocarriers such as liposomes, polymeric nanoparticles, gold nanoparticles, and framework nucleic acids have been used to bring drugs across the skin barrier to epidermis and dermis layers. This article reviews the development of these formulations and focuses on their applications in the treatment of skin disorders such as acne, skin inflammation, skin infection, and wound healing. Existing hurdles and further developments are also discussed.

Nanocarriers

Solid lipid nanoparticle

Skin Barrier

Epidermis (zoology)

Systemic circulation

10.1021/acs.molpharmaceut.0c00154

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Citations (45)