Development of a novel 3D hydrogel for tissue engineering and microfluidics applications

Millions of patients suffer from end-stage organ failure and tissue loss each year. The most practical approach to this problem is the use of standard therapies such as tissue and organ transplantation, with the consequence of limited organ and tissue donors. To address this growing issued, a new method combining cells and biomaterials has been introduced—namely tissue engineering (TE). TE is an interdisciplinary field that applies the ideology of engineering and life sciences toward the development of biological substitutes that maintain, improve or restore the function of organs or tissue. For the regeneration of tissue to be successful, the fabrication of a porous, 3D, biodegradable, biocompatible scaffold with interconnecting pores and appropriate mechanical strength is required. There have been extensive studies on the efficacy of biocompatible polymeric material hydrogels as 3D tissue scaffolds, ranging from natural to synthetic polymers with the ability to degrade and function as “smart” hydrogels, as well as in the microfluidics field. However, the use of modified cellulose as a 3D tissue scaffold has yet to be fully exploited. In this study, a novel biodegradable and macroporous scaffold—a modified cellulose, called hydroxypropyl cellulose (HPC)—has been synthesized with methacrylate anhydride (MA), resulting in bifunctional hydroxypropyl cellulose methacrylate (HPC-MA). HPC-MA hydrogel scaffolds with open biphasic feature were prepared by exploiting the thermal responsive phase behavior of HPC and temperature mediated phase separation of HPC-MA. The resulting scaffolds exhibited pore size ranging from 30 to 300 μm and interconnected porosity of ~90 %. The swelling ratio (SR) and storage modulus of HPC-MA scaffolds were in the range of 12.94 to 35.83 and 0.75 to 4.28 kPa respectively. The swelling ratio and storage modulus suggested that the scaffold exhibits high water retention, allowing medium exchange during cell culturing and making it suitable for adipose tissue regeneration. The HPC-MA scaffolds were found to be biocompatible to human adipose-derived stem cells (ASCs). ASCs were successfully differentiated into adipocytes inside the scaffolds. Success in the fabrication of the HPC-MA scaffold led to the development of a thermo-sensitive cellulosic membrane for cell grafting through the use of the temperature responsive properties of HPC. The resultant macromonomer retains the characteristic thermo-responsive phase behavior of HPC, with an onset temperature of 36 C and a lower critical solution temperature (LCST) of 37~38 oC (as determined by turbidity measurement). The hydrogels exhibited temperature-dependent surface hydrophilicity/hydrophobicity, equilibrium water content and mechanical properties. Cell-releasing characteristics were demonstrated using African green monkey kidney cell line (COS-7 cells) and Murine-derived embryonic stem (Oct4b2) cell line. When the temperature was dropped to 4 oC, the cultivated cells spontaneously detached from the hydrogels without trypsin treatment. These unique properties make the HPC-MA membrane a potential substrate for cell sheet engineering. Another application of the HPC-MA is the fabrication of a freestanding and degradable hybrid paper microfluidic device for bioengineering applications. Paper-based microfluidic devices are emerging as a promising point-of-care diagnostic technology due to their fabrication simplicity, cost effectiveness and versatility. In this study, a method was developed to prepare hybrid paper microfluidic devices where modified cellulose is crosslinked to form a freestanding, paper-like construct that provides a stable structure in an aqueous environment. The resulting HPC construct is a hybrid that possesses the properties of both paper and hydrogel. The hybrid construct has good mechanical properties and can provide structural support for cell anchorage. The feasibility of functionalising these HPC structures with biochemical cues was verified post fabrication, and they were shown to facilitate the adhesion of mesenchymal progenitor cells. The usefulness of this hybrid paper device for a protein assay has also been demonstrated. The HPC structures were found to be biocompatible and hydrolytically degradable, thus enabling cell proliferation and cell migration and thereby constituting an ideal candidate for long-term cell culture and tissue scaffold applications

Development of a novel 3D hydrogel for tissue engineering and microfluidics applications

Millions of patients suffer from end-stage organ failure and tissue loss each year. The most practical approach to this problem is the use of standard therapies such as tissue and organ transplantation, with the consequence of limited organ and tissue donors. To address this growing issued, a new method combining cells and biomaterials has been introduced—namely tissue engineering (TE). TE is an interdisciplinary field that applies the ideology of engineering and life sciences toward the development of biological substitutes that maintain, improve or restore the function of organs or tissue. For the regeneration of tissue to be successful, the fabrication of a porous, 3D, biodegradable, biocompatible scaffold with interconnecting pores and appropriate mechanical strength is required. There have been extensive studies on the efficacy of biocompatible polymeric material hydrogels as 3D tissue scaffolds, ranging from natural to synthetic polymers with the ability to degrade and function as “smart” hydrogels, as well as in the microfluidics field. However, the use of modified cellulose as a 3D tissue scaffold has yet to be fully exploited. In this study, a novel biodegradable and macroporous scaffold—a modified cellulose, called hydroxypropyl cellulose (HPC)—has been synthesized with methacrylate anhydride (MA), resulting in bifunctional hydroxypropyl cellulose methacrylate (HPC-MA). HPC-MA hydrogel scaffolds with open biphasic feature were prepared by exploiting the thermal responsive phase behavior of HPC and temperature mediated phase separation of HPC-MA. The resulting scaffolds exhibited pore size ranging from 30 to 300 μm and interconnected porosity of ~90 %. The swelling ratio (SR) and storage modulus of HPC-MA scaffolds were in the range of 12.94 to 35.83 and 0.75 to 4.28 kPa respectively. The swelling ratio and storage modulus suggested that the scaffold exhibits high water retention, allowing medium exchange during cell culturing and making it suitable for adipose tissue regeneration. The HPC-MA scaffolds were found to be biocompatible to human adipose-derived stem cells (ASCs). ASCs were successfully differentiated into adipocytes inside the scaffolds. Success in the fabrication of the HPC-MA scaffold led to the development of a thermo-sensitive cellulosic membrane for cell grafting through the use of the temperature responsive properties of HPC. The resultant macromonomer retains the characteristic thermo-responsive phase behavior of HPC, with an onset temperature of 36 C and a lower critical solution temperature (LCST) of 37~38 oC (as determined by turbidity measurement). The hydrogels exhibited temperature-dependent surface hydrophilicity/hydrophobicity, equilibrium water content and mechanical properties. Cell-releasing characteristics were demonstrated using African green monkey kidney cell line (COS-7 cells) and Murine-derived embryonic stem (Oct4b2) cell line. When the temperature was dropped to 4 oC, the cultivated cells spontaneously detached from the hydrogels without trypsin treatment. These unique properties make the HPC-MA membrane a potential substrate for cell sheet engineering. Another application of the HPC-MA is the fabrication of a freestanding and degradable hybrid paper microfluidic device for bioengineering applications. Paper-based microfluidic devices are emerging as a promising point-of-care diagnostic technology due to their fabrication simplicity, cost effectiveness and versatility. In this study, a method was developed to prepare hybrid paper microfluidic devices where modified cellulose is crosslinked to form a freestanding, paper-like construct that provides a stable structure in an aqueous environment. The resulting HPC construct is a hybrid that possesses the properties of both paper and hydrogel. The hybrid construct has good mechanical properties and can provide structural support for cell anchorage. The feasibility of functionalising these HPC structures with biochemical cues was verified post fabrication, and they were shown to facilitate the adhesion of mesenchymal progenitor cells. The usefulness of this hybrid paper device for a protein assay has also been demonstrated. The HPC structures were found to be biocompatible and hydrolytically degradable, thus enabling cell proliferation and cell migration and thereby constituting an ideal candidate for long-term cell culture and tissue scaffold applications

Hydroxypropyl cellulose methacrylate as a photo-patternable and biodegradable hybrid paper substrate for cell culture and other bioapplications

In addition to the choice of appropriate material properties of the tissue construct to be used, such as its biocompatibility, biodegradability, cytocompatibility, and mechanical rigidity, the ability to incorporate microarchitectural patterns in the construct to mimic that found in the cellular microenvironment is an important consideration in tissue engineering and regenerative medicine. Both these issues are addressed by demonstrating a method for preparing biodegradable and photo-patternable constructs, where modified cellulose is cross-linked to form an insoluble structure in an aqueous environment. Specifically, hydroxypropyl cellulose (HPC) is rendered photocrosslinkable by grafting with methylacrylic anhydride, whose linkages also render the cross-linked construct hydrolytically degradable. The HPC is then cross-linked via a photolithography-based fabrication process. The feasibility of functionalizing these HPC structures with biochemical cues is verified post-fabrication, and shown to facilitate the adhesion of mesenchymal progenitor cells. The HPC constructs are shown to be biocompatible and hydrolytically degradable, thus enabling cell proliferation and cell migration, and therefore constituting an ideal candidate for long-term cell culture and implantable tissue scaffold applications. In addition, the potential of the HPC structure is demonstrated as an alternative substrate to paper microfluidic diagnostic devices for protein and cell assays

A Novel Tri-Functionality pH-Magnetic-Photocatalytic Hybrid Organic-Inorganic Polyoxometalates Augmented Microspheres for Polluted Water Treatment

The severe water pollution from effluent dyes threatens human health. This study created pH-magnetic-photocatalytic polymer microspheres to conveniently separate the photocatalyst nanoparticles from the treated water by applying an external magnetic field. While fabricating magnetic nanoparticles’ (MNPs) microspheres, incorporating 0.5 wt.% iron oxide (Fe3O4) showed the best magnetophoretic separation ability, as all the MNPs microspheres were attracted toward the external magnet. Subsequently, hybrid organic–inorganic polyoxometalates (HPOM), a self-synthesized photocatalyst, were linked with the functionalized magnetic nanoparticles (f-MNPs) to prepare augmented magnetic-photocatalytic microspheres. The photodegradation dye removal efficiency of the augmented magnetic-photocatalytic microspheres (f-MNPs-HPOM) was then compared with that of the commercial titanium dioxide (TiO2) photocatalyst (f-MNPs-TiO2). Results showed that f-MNPs-HPOM microspheres with 74 ± 0.7% photocatalytic removal efficiency better degraded methylene orange (MO) than f-MNPs-TiO2 (70 ± 0.8%) at an unadjusted pH under UV-light irradiation for 90 min. The excellent performance was mainly attributed to the lower band-gap energy of HPOM (2.65 eV), which required lower energy to be photoactivated under UV light. The f-MNPs-HPOM microspheres demonstrated excellent reusability and stability in the photo-decolorization of MO, as the microspheres retained nearly the same removal percentage throughout the three continuous cycles. The degradation rate was also found to follow the pseudo-first-order kinetics. Furthermore, f-MNPs-HPOM microspheres were pH-responsive in the photodegradation of MO and methylene blue (MB) at pH 3 (acidic) and pH 9 (alkaline). Overall, it was demonstrated that using HPOM photocatalysts in the preparation of magnetic-photocatalytic microspheres resulted in better dye degradation than TiO2 photocatalysts

A Novel Tri-Functionality pH-Magnetic-Photocatalytic Hybrid Organic-Inorganic Polyoxometalates Augmented Microspheres for Polluted Water Treatment

The severe water pollution from effluent dyes threatens human health. This study created pH-magnetic-photocatalytic polymer microspheres to conveniently separate the photocatalyst nanoparticles from the treated water by applying an external magnetic field. While fabricating magnetic nanoparticles’ (MNPs) microspheres, incorporating 0.5 wt.% iron oxide (Fe3O4) showed the best magnetophoretic separation ability, as all the MNPs microspheres were attracted toward the external magnet. Subsequently, hybrid organic–inorganic polyoxometalates (HPOM), a self-synthesized photocatalyst, were linked with the functionalized magnetic nanoparticles (f-MNPs) to prepare augmented magnetic-photocatalytic microspheres. The photodegradation dye removal efficiency of the augmented magnetic-photocatalytic microspheres (f-MNPs-HPOM) was then compared with that of the commercial titanium dioxide (TiO2) photocatalyst (f-MNPs-TiO2). Results showed that f-MNPs-HPOM microspheres with 74 ± 0.7% photocatalytic removal efficiency better degraded methylene orange (MO) than f-MNPs-TiO2 (70 ± 0.8%) at an unadjusted pH under UV-light irradiation for 90 min. The excellent performance was mainly attributed to the lower band-gap energy of HPOM (2.65 eV), which required lower energy to be photoactivated under UV light. The f-MNPs-HPOM microspheres demonstrated excellent reusability and stability in the photo-decolorization of MO, as the microspheres retained nearly the same removal percentage throughout the three continuous cycles. The degradation rate was also found to follow the pseudo-first-order kinetics. Furthermore, f-MNPs-HPOM microspheres were pH-responsive in the photodegradation of MO and methylene blue (MB) at pH 3 (acidic) and pH 9 (alkaline). Overall, it was demonstrated that using HPOM photocatalysts in the preparation of magnetic-photocatalytic microspheres resulted in better dye degradation than TiO2 photocatalysts

Preparation of a soft and interconnected macroporous hydroxypropyl cellulose methacrylate scaffold for adipose tissue engineering

This study describes the preparation and characterization of a biodegradable 3D hydrogel constructed from hydroxypropyl cellulose (HPC), modified with bifunctional methacrylic anhydride (MA) to form hydroxypropyl cellulose methacrylate (HPC-MA), for adipose tissue engineering applications. The hydrogels were prepared from three different concentrations (10 wt percent, 15 wt per cent and 20 wt percent) of HPC-MA with 0.35 degree of substitution. HPC-MA hydrogel scaffolds with open biphasic features were prepared by exploiting the thermal responsive phase behavior of HPC and temperature mediated phase separation of HPC-MA. The resulting scaffolds exhibited pore sizes ranging from 30 to 300 mm and an interconnected porosity ninety percent. The swelling ratio (SR) and storage modulus of HPC-MA scaffolds were in the range of 12.94 to 35.83 and 0.75 to 4.28 kPa, respectively. The swelling ratio and storage modulus suggested that the scaffold exhibits high water retention, allowing medium exchange during cell culturing and that it is suitable for adipose tissue regeneration. The HPC-MA scaffolds were found to be biocompatible to human adipose-derived stem cells (ASCs). ASCs were successfully differentiated into the adipocytes inside the scaffolds, and therefore demonstrated the potential application of these HPC-MA scaffolds for adipose tissue engineering

Validation of the Malay Version of the COVID-19 Anxiety Scale in Malaysia

Background: Malaysians are disillusioned with the increased number of COVID-19 infection cases and the prolonged lockdown period. As a result of COVID-19 mitigation measurements, Malaysians are experiencing emotional and psychological consequences such as anxiety. Thus, there is an urgent need to have an instrument that could serve as a tool to assess the psychological impact of COVID-19 among Malaysians rapidly. Methods: This study aimed to adapt and validate the Malay version of the COVID-19 Anxiety Scale (M-CAS) among Malaysian adults. The back-to-back translation was done to produce a M-CAS. Following face validation, M-CAS was self-administered to 225 participants from Malaysia via an online survey. The participants also completed the Generalised Anxiety Disorder 7-item Scale (GAD-7), World Health Organization Quality of Life Scale, Abbreviated Version (WHOQOL-BREF) and the Fear of COVID-19 Scale (FCV-19S). Data analysis was conducted using Statistical Package for the Social Sciences and Analysis of a Moment Structures. The psychometric properties of the M-CAS were examined via Cronbach alpha and confrmatory factor analysis. M-CAS scores were compared with the other tools to provide external validity. Results: The statistical analysis revealed that the M-CAS demonstrated adequate internal consistency (Cronbach’s alpha = 0.890) and presented with a unidimensional factor structure. M-CAS scores were strongly correlated with GAD-7 (r = 0.511, P < 0.001) and FCV-19S (r = 0.652, P < 0.001). Lack of correlation between M-CAS and WHOQOL-BREF showed that M-CAS scores did not reflect perceived quality of life. Conclusion: The M-CAS is a valid and reliable tool in the Malay language that can be selfadministered among Malaysians to assess anxiety levels induced by COVID-19. The M-CAS has only 7 items and utilised little time in real-life clinical practice