Tzu-Wei Wang - Academia.edu (original) (raw)

Papers by Tzu-Wei Wang

PubMed, 2003

The increasing survival rate of massive burn patients, whose available donor sites for autografti... more The increasing survival rate of massive burn patients, whose available donor sites for autografting are very limited, results in the emerging development and requirement of artificial skin [1-4]. The objective of this study is to produce cultured autologous keratinocyte grafts and to develop an optimal skin substitute for permanent wound closure. In the development of skin equivalent, human dermal fibroblasts were seeded to form three-dimensional dermal replacement tissue. The keratinocytes were initially cultured in keratinocyte serum free medium supplied with epidermal growth factor (EGF). After two days, the medium was changed to keratinocyte basal medium (without EGF) and subsequently cultured for 14 days by the air-liquid interface culture method. We found that time modulation of EGF has great effect on keratinocyte cell behavior. It is suggested that epidermal keratinocytes with bimedium culture system developed the basement membrane and also differentiated upward in the form of multi-layers.

Biomaterials advances, Mar 1, 2023

Biomedical Engineering: Applications, Basis and Communications, Jun 25, 2006

Materials Science Forum, Mar 1, 2018

Mesoporous magnetic hydroxyapatite nanocrystals (MPmHAp NCs) were successfully prepared through o... more Mesoporous magnetic hydroxyapatite nanocrystals (MPmHAp NCs) were successfully prepared through one-step co-precipitate process. From the results, the MPmHAp NCs kept HAp lattice structure and had short rod-like morphology with superparamagnetic property. The size of MPmHAp was 60-80 nm in length and 10-20 nm in width. It also had excellent cell viability when coculture with 3T3 cells in vitro. In addition, MPmHAp NCs not only possessed mesoporous architecture with high surface area for effective drug loading capacity and drug release. The above results indicate that the biocompatible MPmHAp NCs showed great potential as multifunctional therapeutic nanoagent for biomedical application.

PubMed, 2003

The skin consists of epidermis and dermis. In order to develop a biomimetic material for more rea... more The skin consists of epidermis and dermis. In order to develop a biomimetic material for more realistic tissue regeneration, we fabricated a double layer gelatin sponge with different pore sizes by freeze-drying at different temperatures -20 [symbol: see text] and -196 [symbol: see text], respectively. A pseudo microporous structure, which provided the paracrine crosstalk in epithelial-mesenchymal interactions similar to the basement membrane in epidermal-dermal junction was formed between this two compartment. Chrondroitin-6-Sulphate (C-6-S) and hyaluronic acid (HA) were incorporated within the gelatin scaffold to create an appropriate microenvironment for cell proliferation and migration. The mechanical strength of gelatin sponges was improved by cross-linking of gelatin with carbodiimide in 95% ethanol solution two times. The lattice structure and pore sizes were evaluated by SEM to confirm that the interconnected porous structures were retained. We chose a dynamic spinner flask seeding method for more even distribution followed by a culture system in the air-liquid interface cultured for 21 days. Differentiation and phenotypic expression of keratinocytes were investigated by histological analysis and immunohistochemical identification. In this study, we found multiple epidermis-like layers constructed by cultured keratinocytes. It is suggested that the bi-layer scaffolds have the potential to be used as skin equivalents for application in burn wounds. In the future, the qualitative of chemical reagents and in vivo animal model tests will be evaluated.

Biofabrication, Feb 28, 2017

In these years, the artificial nerve guidance conduit has been developed as an alternative way to... more In these years, the artificial nerve guidance conduit has been developed as an alternative way to repair peripheral nerve injury. Unlike autologous nerve graft, the artificial nerve guidance conduit without proper stimulating factors and guidance cues still cannot obtain satisfactory prognosis for clinical patients. In this study, a biodegradable polymer-based implantable device has been developed and characterized. By incorporating three stimulating factors: 1) micro-patterned surface that can directionally guide the axon as physical cue; 2) neurotrophic gradient membrane that can continually attract axon outgrowth from the proximal to distal stump as chemical cue; 3) Schwann cells that can support the growth of neurite and form myelin sheath around axon as biological cue, we expect that this construct can be used as a promising nerve guidance conduit for peripheral nerve regeneration. The results showed that the micro-patterned surface with specific dimension of channels and chambers can be precisely fabricated by laser ablation. Attachment and directional extension of differentiated neural stem cells were observed in micro-channels. The gradient distribution of nerve growth factor 7S on gelatin membrane was successfully achieved. Significant improvement in neurite length and increase in neuronal gene expressions were also noticed in higher concentration region. When co-culturing with Schwann cells, neural stem cells can differentiate toward neuronal cells with strong expression of mature neuronal markers: βIII tubulin and microtubule-associated protein-2 (Map 2). Meanwhile, myelin basic protein (MBP) was also observed, suggesting that Schwann cells can provide biological support to neuronal cells in vitro. In the future, this advanced artificial nerve guidance conduit may be used as implantable prosthesis for the treatment of peripheral nerve injury with better functional recovery.

Acta Biomaterialia, Aug 1, 2017

Breast cancer has become the second leading cause of cancer-related mortality in female wherein m... more Breast cancer has become the second leading cause of cancer-related mortality in female wherein more than 90% of breast cancer-related death results from cancer metastasis to distant organs at advanced stage. The purpose of this study is to develop biodegradable nanoparticles composed of natural polypeptides and calcium phosphate (CaP) with sequential pH-responsivity to tumor microenvironments for active targeted drug delivery. Two different amphiphilic copolymers, poly(ethylene glycol) 3400-aconityl linkage-poly(L-glutamic acid) 15-poly(Lhistidine) 10-poly(L-leucine) 10 and LyP1-poly(ethylene glycol) 1100-poly(L-glutamic acid) 15-poly(Lhistidine) 10-poly(L-leucine) 10 , were exploited to self-assemble into micelles in aqueous phase. The bio-stable nanoparticles provide three distinct functional domains: the anionic PGlu shell for CaP mineralization, the protonation of PHis segment for facilitating anticancer drug release at target site, and the hydrophobic core of PLeu for encapsulation of anticancer drugs. Furthermore, the hydrated PEG outer corona is used for prolonging circulation time, while the active targeting ligand, LyP-1, is served to bind to breast cancer cells and lymphatic endothelial cells in tumor for inhibiting metastasis. Mineralized DOX-loaded nanoparticles (M-DOX NPs) efficiently prevent the drug leakage at physiological pH value and facilitate the encapsulated drug release at acidic condition when compared to DOX-loaded nanoparticles (DOX NPs). M-DOX NPs with LyP-1 targeting ligand effectively accumulated in MDA-MB-231 breast cancer cells. The inhibition effect on cell proliferation also enhances with time, illustrating the prominent anti-tumor efficacy. Moreover, the in vitro metastatic inhibition model shows the profound inhibition effect of inhibitory nanoparticles. In brief, this self-assembling peptide-based drug delivery nanocarrier with multifunctionality and programmable pH-sensitivity is of great promise and potential for anti-cancer therapy. Statement of Significance This tailored-design polypeptide-based nanoparticles with self-assembling and programmable stimulus-responsive properties enable to 1) be stable in physiological pH value with a low level of drug loss and effectively release the encapsulated drug with pH variations according to the tumor microenvironment, 2) enhanced targeting ability to hardto-treat breast cancer cells and activated endothelial cells (tumor region), 3) significantly inhibit the growth and prevent from malignant metastasis of cancer cells in consonance with promising anti-tumor efficacy, and 4) keep tumors stick to localized position so that these confined solid tumors can be more accessible by different treatment modalities. The contribution of this work is how to design a programmable pH-responsive drug delivery system based on the tailor-designed polypeptides.

Biomaterials, Jun 1, 2016

Integrated self-assembling drug delivery system possessing dual responsive and active targeting f... more Integrated self-assembling drug delivery system possessing dual responsive and active targeting for orthotopic ovarian cancer theranostics, Biomaterials (2016),

Advanced Functional Materials, Jan 8, 2010

ACS Applied Materials & Interfaces, Oct 17, 2017

Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patient... more Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patients annually. It is therefore important to incorporate different strategies to promote nerve healing. Among the treatment options, however, the efficacy of nerve conduits is often compromised by their lack of living cells, insufficient growth factors and absence of the extracellular matrix (ECM)-like structure. To improve the functional recovery, we aimed to develop a natural biodegradable multi-channeled scaffold characterized with aligned electrospun nanofibers and neurotrophic gradient (MC/AN/NG) to guide axon outgrowth. The gelatin-based conduits mimicked the fascicular architecture of natural nerve ECM. The multi-channeled (MC) scaffolds, crosslinked with microbial transglutaminase, possessed sustainable mechanical stability. Meanwhile, the release profile of dual neurotrophic factors: nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF) exhibited a temporal-controlled manner. In vitro, the differentiated neural stem cells effectively extended their neurites along the aligned nanofibers. Besides, in the treated group, the cell density increased in high NGF concentration regions of the gradient membrane, and the BDNF significantly promoted myelination. In a rabbit sciatic nerve transection in vivo model, the MC/AN/NG scaffold showed superior nerve recovery and less muscle atrophy comparable to autograft. By integrating multiple strategies to promote peripheral nerve regeneration, the MC/AN/NG scaffolds as nerve guidance conduits showed promising results and efficacious treatment alternatives for autologous nerve grafts.

Acta Biomaterialia, Sep 1, 2009

Trans Tech Publications Ltd. eBooks, Feb 15, 2006

Three-dimensional gelatin-chondroitin 6 sulphate-hyanuronic acid biomatrix was used as the scaffo... more Three-dimensional gelatin-chondroitin 6 sulphate-hyanuronic acid biomatrix was used as the scaffold to investigate the phenotypic and molecular expression in human keratinocytes (K) and dermal fibroblasts (FB) in three different culture conditions in vitro. The cells were cultured in either monolayer (K or FB only) or coculture (K&FB) model. The deposition of basement membrane proteins secreted by these two kinds of cells was quantitatively characterized by real-time PCR. In the results, dermal fibroblasts were shown to synthesize and deposit laminin 5, type IV and type VII collagen, whereas keratinocytes produced integrin alpha 6 and beta 4 as well as laminin 5 and collagen type IV, VII. Interestingly, the integrin beta 4 subunit was not expressed either in keratinocytes or dermal fibroblasts monoculture but was seen in organotypic coculture model in the early culture period. Furthermore, we found that the expression of those marker compounds was reciprocally regulated when keratinocytes and dermal fibroblasts were cultured together. These results indicated that keratinocyes and dermal fibroblasts worked together to reconstruct dermal-epidermal basement membrane (BM) zone. In brief, our data provide the first time in directly quantifying the expression of BM proteins by using real-time PCR, and also demonstrate that BM proteins were regulated by cell-cell interaction.

Trans Tech Publications Ltd. eBooks, Feb 15, 2006

ABSTRACT

Research Square (Research Square), Oct 31, 2023

Current synthetic grafts for ligament rupture repair often fail to integrate well with the surrou... more Current synthetic grafts for ligament rupture repair often fail to integrate well with the surrounding biological tissue, leading to complications such as graft wear, fatigue, and subsequent re-rupture. To address this medical challenge, this study aims at advancing the development of a biological ligament through the integration of physiologically-inspired principles and tissue engineering strategies. In this study, we utilize interfacial polyelectrolyte complexation spinning technique, along with a customdesigned collection system, to fabricate a hierarchical scaffold mimicking native ligament structure. To emulate the bone-ligament interface and alleviate stress concentration, a hydroxyapatite mineral gradient is strategically introduced near both ends of the scaffold to enhance interface integration and diminish the risk of avulsion rupture. Biomimetic viscoelasticity is successfully displayed to provide similar mechanical support to native ligamentous tissue under physiological conditions. By introducing the connective tissue growth factor and conducting mesenchymal stem cells transplantation, we signi cantly amplify the regenerative potential of the synthetic ligament. This pioneering study offers a multifaceted solution combining biomimetic materials, regenerative therapies, and advanced techniques to potentially transform ligament rupture treatment. The highlights of this research are Ligament-like hierarchical architecture is developed to closely mimic the hierarchical ber organization of ligaments and act as a structural cue for de novo tissue generation. Enthesis-like hydroxyapatite gradient is incorporated to promote transition from soft to hard tissue and enhance ligament-to-bone interface healing. Biomimetic viscoelasticity is created to provide similar mechanical support to native ligametous tissue under physiological conditions. Tissue-engineered strategies including MSC inoculation and growth factor delivery are included to improve the regenerative outcome.

Biomaterials, Mar 1, 2013

Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowa... more Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowadays, new therapeutic strategies have been focused on stem cell therapy and supplying an appropriate three dimensional (3D) matrix for the repair of injured brain tissue. In this study, we specifically linked laminin-derived IKVAV motif on the C-terminal to enrich self-assembling peptide RADA(16) as a functional peptide-based scaffold. Our purpose is providing a functional self-assembling peptide 3D hydrogel with encapsulated neural stem cells to enhance the reconstruction of the injured brain. The physiochemical properties reported that RADA(16)-IKVAV can self-assemble into nanofibrous morphology with bilayer β-sheet structure and become gelationed hydrogel with mechanical stiffness similar to brain tissue. The in vitro results showed that the extended IKVAV sequence can serve as a signal or guiding cue to direct the encapsulated neural stem cells (NSCs) adhesion and then towards neuronal differentiation. Animal study was conducted in a rat brain surgery model to demonstrate the damage in cerebral neocortex/neopallium loss. The results showed that the injected peptide solution immediately in situ formed the 3D hydrogel filling up the cavity and bridging the gaps. The histological analyses revealed the RADA(16)-IKVAV self-assembling peptide hydrogel not only enhanced survival of encapsulated NSCs but also reduced the formation of glial astrocytes. The peptide hydrogel with IKVAV extended motifs also showed the support of encapsulated NSCs in neuronal differentiation and the improvement in brain tissue regeneration after 6 weeks post-transplantation.

Social Science Research Network, 2022

ACS Biomaterials Science & Engineering, Jul 29, 2021

Heterogeneous tissue models require the assembly and co-culture of multiple types of cells. Our r... more Heterogeneous tissue models require the assembly and co-culture of multiple types of cells. Our recent work demonstrated taste signal transmission from gustatory cells to neurons by grafting single-stranded DNA into the cell membrane to construct multicellular assemblies. However, the weak DNA linkage and low grafting density allowed the formation of large gustatory cell self-aggregates that cannot communicate with neurons efficiently. This article presents the construction of artificial taste buds exhibiting active intercellular taste signal transmission through the hybridization of gustatory-neuronal multicellular interfaces using bioorthogonal click chemistry. Hybrid cell clusters were formed by the self-assembly of neonatal gustatory cells displaying tetrazine with a precultured embryonic hippocampal neuronal network displaying trans-cyclooctene. A bitter taste signal transduction was provoked in gustatory cells using denatonium benzoate and transmitted to neurons as monitored by intracellular calcium ion sensing. In the multicellular hybrids, the average number of signal transmissions was five to six peaks per cell, and the signal transmission lasted for ∼5 min with a signal-to-signal gap time of 10-40 s. The frequent and extended intercellular signal transmission suggests that the cell surface modification by the bioorthogonal click chemistry is a promising approach to fabricating functional multicellular hybrid clusters potentially useful for cell-based biosensors, toxicity assays, and tissue regeneration.

RSC Advances, 2013

ABSTRACT In this study, an environmentally-sensitive hyaluronic acid (HA)-polyethylenimine (PEI) ... more ABSTRACT In this study, an environmentally-sensitive hyaluronic acid (HA)-polyethylenimine (PEI) copolymer with disulfide linkage is synthesized, characterized and examined as a potential non-viral gene vector. From the results, a redox- and pH-sensitive gene delivery nanocarrier has been successfully synthesized via the analysis of 1H NMR and FT-IR. The positive HA-ss-PEI conjugate complexed with negatively charged plasmid DNA can be achieved via electrostatic attraction to form a stable spherical nanoparticle of 100 to 200 nm in diameter. N/P = 2 possesses the optimal condition for releasing encapsulated plasmid when triggered by stimuli such as redox reaction and pH change. The HA-ss-PEI/pEndo nanocarrier can transfect human mesenchymal stem cells to produce endostatin protein and these hMSCs are capable of differentiating into functional chondrocytes after 7 days chondrogenic induction. The nano-encapsulation of genetic anti-angiogenesis factor combined with the chondrogenic induction of hMSCs may offer an alternative choice and potentially effective administration strategy for arthritis.

Current Nanoscience, Dec 1, 2011

In this study, synthetic hydroxyapatite nanoparticles (Hap NPs) were rendered magnetic by treatme... more In this study, synthetic hydroxyapatite nanoparticles (Hap NPs) were rendered magnetic by treatment with iron ions using a wet-chemical process. The magnetized Hap (mHap) NPs were fabricated by the addition of iron precursor in various ratios of Fe:Ca (XFe/ Ca). The physicochemical properties of mHap NPs were evaluated respectively, by X-ray diffraction (XRD) for the crystal structure, Fourier transform infrared (FTIR) spectroscopy for functional groups detection, Energy-Dispersive X-ray Spectroscopy (EDS) for composition analysis , transmission electron microscopy (TEM) for particle morphology characterization, and superconducting quantum interference device (SQUID) for magnetization property. The size distribution of mHap randomly in rod and needle-like shape was in average 80 to 120 nm. We found that the mHap was the result of the hetero-epitaxial growth of magnetite on the Hap crystallites. The magnetic NPs with sphere shape less than 10 nm in diameters were tightly surrounded on Hap crystallites and possessed superparamagnetic property. The magnetization of all groups of mHap NPs increased with the increasing of XFe/ Ca and with no toxic effect to cultured cells. In brief, mHap NPs demonstrated suitable physicochemical properties and good biocompatibility, suggesting that these NPs have potential applications as new biodegradable MRI contrast agent in medicine.

PubMed, 2003

The increasing survival rate of massive burn patients, whose available donor sites for autografti... more The increasing survival rate of massive burn patients, whose available donor sites for autografting are very limited, results in the emerging development and requirement of artificial skin [1-4]. The objective of this study is to produce cultured autologous keratinocyte grafts and to develop an optimal skin substitute for permanent wound closure. In the development of skin equivalent, human dermal fibroblasts were seeded to form three-dimensional dermal replacement tissue. The keratinocytes were initially cultured in keratinocyte serum free medium supplied with epidermal growth factor (EGF). After two days, the medium was changed to keratinocyte basal medium (without EGF) and subsequently cultured for 14 days by the air-liquid interface culture method. We found that time modulation of EGF has great effect on keratinocyte cell behavior. It is suggested that epidermal keratinocytes with bimedium culture system developed the basement membrane and also differentiated upward in the form of multi-layers.

Biomaterials advances, Mar 1, 2023

Biomedical Engineering: Applications, Basis and Communications, Jun 25, 2006

Materials Science Forum, Mar 1, 2018

Mesoporous magnetic hydroxyapatite nanocrystals (MPmHAp NCs) were successfully prepared through o... more Mesoporous magnetic hydroxyapatite nanocrystals (MPmHAp NCs) were successfully prepared through one-step co-precipitate process. From the results, the MPmHAp NCs kept HAp lattice structure and had short rod-like morphology with superparamagnetic property. The size of MPmHAp was 60-80 nm in length and 10-20 nm in width. It also had excellent cell viability when coculture with 3T3 cells in vitro. In addition, MPmHAp NCs not only possessed mesoporous architecture with high surface area for effective drug loading capacity and drug release. The above results indicate that the biocompatible MPmHAp NCs showed great potential as multifunctional therapeutic nanoagent for biomedical application.

PubMed, 2003

The skin consists of epidermis and dermis. In order to develop a biomimetic material for more rea... more The skin consists of epidermis and dermis. In order to develop a biomimetic material for more realistic tissue regeneration, we fabricated a double layer gelatin sponge with different pore sizes by freeze-drying at different temperatures -20 [symbol: see text] and -196 [symbol: see text], respectively. A pseudo microporous structure, which provided the paracrine crosstalk in epithelial-mesenchymal interactions similar to the basement membrane in epidermal-dermal junction was formed between this two compartment. Chrondroitin-6-Sulphate (C-6-S) and hyaluronic acid (HA) were incorporated within the gelatin scaffold to create an appropriate microenvironment for cell proliferation and migration. The mechanical strength of gelatin sponges was improved by cross-linking of gelatin with carbodiimide in 95% ethanol solution two times. The lattice structure and pore sizes were evaluated by SEM to confirm that the interconnected porous structures were retained. We chose a dynamic spinner flask seeding method for more even distribution followed by a culture system in the air-liquid interface cultured for 21 days. Differentiation and phenotypic expression of keratinocytes were investigated by histological analysis and immunohistochemical identification. In this study, we found multiple epidermis-like layers constructed by cultured keratinocytes. It is suggested that the bi-layer scaffolds have the potential to be used as skin equivalents for application in burn wounds. In the future, the qualitative of chemical reagents and in vivo animal model tests will be evaluated.

Biofabrication, Feb 28, 2017

In these years, the artificial nerve guidance conduit has been developed as an alternative way to... more In these years, the artificial nerve guidance conduit has been developed as an alternative way to repair peripheral nerve injury. Unlike autologous nerve graft, the artificial nerve guidance conduit without proper stimulating factors and guidance cues still cannot obtain satisfactory prognosis for clinical patients. In this study, a biodegradable polymer-based implantable device has been developed and characterized. By incorporating three stimulating factors: 1) micro-patterned surface that can directionally guide the axon as physical cue; 2) neurotrophic gradient membrane that can continually attract axon outgrowth from the proximal to distal stump as chemical cue; 3) Schwann cells that can support the growth of neurite and form myelin sheath around axon as biological cue, we expect that this construct can be used as a promising nerve guidance conduit for peripheral nerve regeneration. The results showed that the micro-patterned surface with specific dimension of channels and chambers can be precisely fabricated by laser ablation. Attachment and directional extension of differentiated neural stem cells were observed in micro-channels. The gradient distribution of nerve growth factor 7S on gelatin membrane was successfully achieved. Significant improvement in neurite length and increase in neuronal gene expressions were also noticed in higher concentration region. When co-culturing with Schwann cells, neural stem cells can differentiate toward neuronal cells with strong expression of mature neuronal markers: βIII tubulin and microtubule-associated protein-2 (Map 2). Meanwhile, myelin basic protein (MBP) was also observed, suggesting that Schwann cells can provide biological support to neuronal cells in vitro. In the future, this advanced artificial nerve guidance conduit may be used as implantable prosthesis for the treatment of peripheral nerve injury with better functional recovery.

Acta Biomaterialia, Aug 1, 2017

Breast cancer has become the second leading cause of cancer-related mortality in female wherein m... more Breast cancer has become the second leading cause of cancer-related mortality in female wherein more than 90% of breast cancer-related death results from cancer metastasis to distant organs at advanced stage. The purpose of this study is to develop biodegradable nanoparticles composed of natural polypeptides and calcium phosphate (CaP) with sequential pH-responsivity to tumor microenvironments for active targeted drug delivery. Two different amphiphilic copolymers, poly(ethylene glycol) 3400-aconityl linkage-poly(L-glutamic acid) 15-poly(Lhistidine) 10-poly(L-leucine) 10 and LyP1-poly(ethylene glycol) 1100-poly(L-glutamic acid) 15-poly(Lhistidine) 10-poly(L-leucine) 10 , were exploited to self-assemble into micelles in aqueous phase. The bio-stable nanoparticles provide three distinct functional domains: the anionic PGlu shell for CaP mineralization, the protonation of PHis segment for facilitating anticancer drug release at target site, and the hydrophobic core of PLeu for encapsulation of anticancer drugs. Furthermore, the hydrated PEG outer corona is used for prolonging circulation time, while the active targeting ligand, LyP-1, is served to bind to breast cancer cells and lymphatic endothelial cells in tumor for inhibiting metastasis. Mineralized DOX-loaded nanoparticles (M-DOX NPs) efficiently prevent the drug leakage at physiological pH value and facilitate the encapsulated drug release at acidic condition when compared to DOX-loaded nanoparticles (DOX NPs). M-DOX NPs with LyP-1 targeting ligand effectively accumulated in MDA-MB-231 breast cancer cells. The inhibition effect on cell proliferation also enhances with time, illustrating the prominent anti-tumor efficacy. Moreover, the in vitro metastatic inhibition model shows the profound inhibition effect of inhibitory nanoparticles. In brief, this self-assembling peptide-based drug delivery nanocarrier with multifunctionality and programmable pH-sensitivity is of great promise and potential for anti-cancer therapy. Statement of Significance This tailored-design polypeptide-based nanoparticles with self-assembling and programmable stimulus-responsive properties enable to 1) be stable in physiological pH value with a low level of drug loss and effectively release the encapsulated drug with pH variations according to the tumor microenvironment, 2) enhanced targeting ability to hardto-treat breast cancer cells and activated endothelial cells (tumor region), 3) significantly inhibit the growth and prevent from malignant metastasis of cancer cells in consonance with promising anti-tumor efficacy, and 4) keep tumors stick to localized position so that these confined solid tumors can be more accessible by different treatment modalities. The contribution of this work is how to design a programmable pH-responsive drug delivery system based on the tailor-designed polypeptides.

Biomaterials, Jun 1, 2016

Integrated self-assembling drug delivery system possessing dual responsive and active targeting f... more Integrated self-assembling drug delivery system possessing dual responsive and active targeting for orthotopic ovarian cancer theranostics, Biomaterials (2016),

Advanced Functional Materials, Jan 8, 2010

ACS Applied Materials & Interfaces, Oct 17, 2017

Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patient... more Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patients annually. It is therefore important to incorporate different strategies to promote nerve healing. Among the treatment options, however, the efficacy of nerve conduits is often compromised by their lack of living cells, insufficient growth factors and absence of the extracellular matrix (ECM)-like structure. To improve the functional recovery, we aimed to develop a natural biodegradable multi-channeled scaffold characterized with aligned electrospun nanofibers and neurotrophic gradient (MC/AN/NG) to guide axon outgrowth. The gelatin-based conduits mimicked the fascicular architecture of natural nerve ECM. The multi-channeled (MC) scaffolds, crosslinked with microbial transglutaminase, possessed sustainable mechanical stability. Meanwhile, the release profile of dual neurotrophic factors: nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF) exhibited a temporal-controlled manner. In vitro, the differentiated neural stem cells effectively extended their neurites along the aligned nanofibers. Besides, in the treated group, the cell density increased in high NGF concentration regions of the gradient membrane, and the BDNF significantly promoted myelination. In a rabbit sciatic nerve transection in vivo model, the MC/AN/NG scaffold showed superior nerve recovery and less muscle atrophy comparable to autograft. By integrating multiple strategies to promote peripheral nerve regeneration, the MC/AN/NG scaffolds as nerve guidance conduits showed promising results and efficacious treatment alternatives for autologous nerve grafts.

Acta Biomaterialia, Sep 1, 2009

Trans Tech Publications Ltd. eBooks, Feb 15, 2006

Three-dimensional gelatin-chondroitin 6 sulphate-hyanuronic acid biomatrix was used as the scaffo... more Three-dimensional gelatin-chondroitin 6 sulphate-hyanuronic acid biomatrix was used as the scaffold to investigate the phenotypic and molecular expression in human keratinocytes (K) and dermal fibroblasts (FB) in three different culture conditions in vitro. The cells were cultured in either monolayer (K or FB only) or coculture (K&FB) model. The deposition of basement membrane proteins secreted by these two kinds of cells was quantitatively characterized by real-time PCR. In the results, dermal fibroblasts were shown to synthesize and deposit laminin 5, type IV and type VII collagen, whereas keratinocytes produced integrin alpha 6 and beta 4 as well as laminin 5 and collagen type IV, VII. Interestingly, the integrin beta 4 subunit was not expressed either in keratinocytes or dermal fibroblasts monoculture but was seen in organotypic coculture model in the early culture period. Furthermore, we found that the expression of those marker compounds was reciprocally regulated when keratinocytes and dermal fibroblasts were cultured together. These results indicated that keratinocyes and dermal fibroblasts worked together to reconstruct dermal-epidermal basement membrane (BM) zone. In brief, our data provide the first time in directly quantifying the expression of BM proteins by using real-time PCR, and also demonstrate that BM proteins were regulated by cell-cell interaction.

Trans Tech Publications Ltd. eBooks, Feb 15, 2006

ABSTRACT

Research Square (Research Square), Oct 31, 2023

Current synthetic grafts for ligament rupture repair often fail to integrate well with the surrou... more Current synthetic grafts for ligament rupture repair often fail to integrate well with the surrounding biological tissue, leading to complications such as graft wear, fatigue, and subsequent re-rupture. To address this medical challenge, this study aims at advancing the development of a biological ligament through the integration of physiologically-inspired principles and tissue engineering strategies. In this study, we utilize interfacial polyelectrolyte complexation spinning technique, along with a customdesigned collection system, to fabricate a hierarchical scaffold mimicking native ligament structure. To emulate the bone-ligament interface and alleviate stress concentration, a hydroxyapatite mineral gradient is strategically introduced near both ends of the scaffold to enhance interface integration and diminish the risk of avulsion rupture. Biomimetic viscoelasticity is successfully displayed to provide similar mechanical support to native ligamentous tissue under physiological conditions. By introducing the connective tissue growth factor and conducting mesenchymal stem cells transplantation, we signi cantly amplify the regenerative potential of the synthetic ligament. This pioneering study offers a multifaceted solution combining biomimetic materials, regenerative therapies, and advanced techniques to potentially transform ligament rupture treatment. The highlights of this research are Ligament-like hierarchical architecture is developed to closely mimic the hierarchical ber organization of ligaments and act as a structural cue for de novo tissue generation. Enthesis-like hydroxyapatite gradient is incorporated to promote transition from soft to hard tissue and enhance ligament-to-bone interface healing. Biomimetic viscoelasticity is created to provide similar mechanical support to native ligametous tissue under physiological conditions. Tissue-engineered strategies including MSC inoculation and growth factor delivery are included to improve the regenerative outcome.

Biomaterials, Mar 1, 2013

Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowa... more Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowadays, new therapeutic strategies have been focused on stem cell therapy and supplying an appropriate three dimensional (3D) matrix for the repair of injured brain tissue. In this study, we specifically linked laminin-derived IKVAV motif on the C-terminal to enrich self-assembling peptide RADA(16) as a functional peptide-based scaffold. Our purpose is providing a functional self-assembling peptide 3D hydrogel with encapsulated neural stem cells to enhance the reconstruction of the injured brain. The physiochemical properties reported that RADA(16)-IKVAV can self-assemble into nanofibrous morphology with bilayer β-sheet structure and become gelationed hydrogel with mechanical stiffness similar to brain tissue. The in vitro results showed that the extended IKVAV sequence can serve as a signal or guiding cue to direct the encapsulated neural stem cells (NSCs) adhesion and then towards neuronal differentiation. Animal study was conducted in a rat brain surgery model to demonstrate the damage in cerebral neocortex/neopallium loss. The results showed that the injected peptide solution immediately in situ formed the 3D hydrogel filling up the cavity and bridging the gaps. The histological analyses revealed the RADA(16)-IKVAV self-assembling peptide hydrogel not only enhanced survival of encapsulated NSCs but also reduced the formation of glial astrocytes. The peptide hydrogel with IKVAV extended motifs also showed the support of encapsulated NSCs in neuronal differentiation and the improvement in brain tissue regeneration after 6 weeks post-transplantation.

Social Science Research Network, 2022

ACS Biomaterials Science & Engineering, Jul 29, 2021

Heterogeneous tissue models require the assembly and co-culture of multiple types of cells. Our r... more Heterogeneous tissue models require the assembly and co-culture of multiple types of cells. Our recent work demonstrated taste signal transmission from gustatory cells to neurons by grafting single-stranded DNA into the cell membrane to construct multicellular assemblies. However, the weak DNA linkage and low grafting density allowed the formation of large gustatory cell self-aggregates that cannot communicate with neurons efficiently. This article presents the construction of artificial taste buds exhibiting active intercellular taste signal transmission through the hybridization of gustatory-neuronal multicellular interfaces using bioorthogonal click chemistry. Hybrid cell clusters were formed by the self-assembly of neonatal gustatory cells displaying tetrazine with a precultured embryonic hippocampal neuronal network displaying trans-cyclooctene. A bitter taste signal transduction was provoked in gustatory cells using denatonium benzoate and transmitted to neurons as monitored by intracellular calcium ion sensing. In the multicellular hybrids, the average number of signal transmissions was five to six peaks per cell, and the signal transmission lasted for ∼5 min with a signal-to-signal gap time of 10-40 s. The frequent and extended intercellular signal transmission suggests that the cell surface modification by the bioorthogonal click chemistry is a promising approach to fabricating functional multicellular hybrid clusters potentially useful for cell-based biosensors, toxicity assays, and tissue regeneration.

RSC Advances, 2013

ABSTRACT In this study, an environmentally-sensitive hyaluronic acid (HA)-polyethylenimine (PEI) ... more ABSTRACT In this study, an environmentally-sensitive hyaluronic acid (HA)-polyethylenimine (PEI) copolymer with disulfide linkage is synthesized, characterized and examined as a potential non-viral gene vector. From the results, a redox- and pH-sensitive gene delivery nanocarrier has been successfully synthesized via the analysis of 1H NMR and FT-IR. The positive HA-ss-PEI conjugate complexed with negatively charged plasmid DNA can be achieved via electrostatic attraction to form a stable spherical nanoparticle of 100 to 200 nm in diameter. N/P = 2 possesses the optimal condition for releasing encapsulated plasmid when triggered by stimuli such as redox reaction and pH change. The HA-ss-PEI/pEndo nanocarrier can transfect human mesenchymal stem cells to produce endostatin protein and these hMSCs are capable of differentiating into functional chondrocytes after 7 days chondrogenic induction. The nano-encapsulation of genetic anti-angiogenesis factor combined with the chondrogenic induction of hMSCs may offer an alternative choice and potentially effective administration strategy for arthritis.

Current Nanoscience, Dec 1, 2011

In this study, synthetic hydroxyapatite nanoparticles (Hap NPs) were rendered magnetic by treatme... more In this study, synthetic hydroxyapatite nanoparticles (Hap NPs) were rendered magnetic by treatment with iron ions using a wet-chemical process. The magnetized Hap (mHap) NPs were fabricated by the addition of iron precursor in various ratios of Fe:Ca (XFe/ Ca). The physicochemical properties of mHap NPs were evaluated respectively, by X-ray diffraction (XRD) for the crystal structure, Fourier transform infrared (FTIR) spectroscopy for functional groups detection, Energy-Dispersive X-ray Spectroscopy (EDS) for composition analysis , transmission electron microscopy (TEM) for particle morphology characterization, and superconducting quantum interference device (SQUID) for magnetization property. The size distribution of mHap randomly in rod and needle-like shape was in average 80 to 120 nm. We found that the mHap was the result of the hetero-epitaxial growth of magnetite on the Hap crystallites. The magnetic NPs with sphere shape less than 10 nm in diameters were tightly surrounded on Hap crystallites and possessed superparamagnetic property. The magnetization of all groups of mHap NPs increased with the increasing of XFe/ Ca and with no toxic effect to cultured cells. In brief, mHap NPs demonstrated suitable physicochemical properties and good biocompatibility, suggesting that these NPs have potential applications as new biodegradable MRI contrast agent in medicine.