ORCID Profile
0000-0003-4756-2644
Current Organisation
Nanyang Technological University
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Publisher: American Chemical Society (ACS)
Date: 06-07-2022
Abstract: Biofunctionalization of silk biomaterial surfaces with extracellular matrix (ECM) molecules, cell binding peptides, or growth factors is important in a range of applications, including tissue engineering and development of implantable medical devices. Passive adsorption is the most common way to immobilize molecules of interest on preformed silk biomaterials but can lead to random molecular orientations and displacement from the surface, limiting their applications. Herein, we developed techniques for covalent immobilization of biomolecules using enzyme- or photoinitiated formation of dityrosine bonds between the molecule of interest and silk. Using recombinantly expressed domain V of the human basement membrane proteoglycan perlecan (rDV) as a model molecule, we demonstrated that rDV can be covalently immobilized via dityrosine cross-linking without the need to modify rDV or silk biomaterials. Dityrosine-based immobilization resulted in a different molecular orientation to passively absorbed rDV with less C- and N-terminal region exposure on the surface. Dityrosine-based immobilization supported functional rDV immobilization where immobilized rDV supported endothelial cell adhesion, spreading, migration, and proliferation. These results demonstrate the utility of dityrosine-based cross-linking in covalent immobilization of tyrosine-containing molecules on silk biomaterials in the absence of chemical modification, adding a simple and accessible technique to the silk biofunctionalization toolbox.
Publisher: Cold Spring Harbor Laboratory
Date: 20-01-2021
DOI: 10.1101/2021.01.19.427349
Abstract: Translation into the clinic of organic bioelectronic devices having conjugated polymers as the active material will hinge on their long-term operation in vivo . This will require the device to be subject to clinically approved sterilization techniques without a deterioration in its physical and electronic properties. To date, there remains a gap in the literature addressing the impact of this critical pre-operative procedure on the properties of conjugated polymers. This study aims to address this gap by assessing the physical and electronic properties of a sterilized porous bioelectronic patch having polyaniline as the conjugated polymer. The patch was sterilized by autoclave, ethylene oxide and gamma (γ-) irradiation at 15, 25, and 50 kGy doses. Autoclaving resulted in cracking and macroscopic degradation of the patch, while patches sterilized by γ-irradiation at 50 kGy exhibited reduced mechanical and electronic properties, attributed to chain scission and non-uniform crosslinking caused by the high dose irradiation. Ethylene oxide and γ-irradiation at 15 and 25 kGy sterilization appeared to be the most effective at maintaining the mechanical and electronic properties of the patch, as well as inducing a minimal immune response as revealed by a receding fibrotic capsule after 4 weeks implantation. Our findings pave the way towards closing the gap for the translation of organic bioelectronic devices from acute to long-term in vivo models.
Publisher: Wiley
Date: 10-03-2023
DOI: 10.1002/JBM.A.37525
Abstract: Strategies to promote rapid formation of functional endothelium are required to maintain blood fluidity and regulate smooth muscle cell proliferation in synthetic vascular conduits. In this work, we explored the biofunctionalization of silk biomaterials with recombinantly expressed domain V of human perlecan (rDV) to promote endothelial cell interactions and the formation of functional endothelium. Perlecan is essential in vascular development and homeostasis and rDV has been shown to uniquely support endothelial cell, while inhibiting smooth muscle cell and platelet interactions, both key contributors of vascular graft failure. rDV was covalently immobilized on silk using plasma immersion ion implantation (PIII), a simple one‐step surface treatment process which enables strong immobilization in the absence of chemical cross‐linkers. rDV immobilization on surface‐modified silk was assessed for amount, orientation, and bio‐functionality in terms of endothelial cell interactions and functional endothelial layer formation. rDV immobilized on PIII‐treated silk (rDV‐PIII‐silk) supported rapid endothelial cell adhesion, spreading, and proliferation to form functional endothelium, as evidenced by the expression of vinculin and VE‐cadherin markers. Taken together, the results provide evidence for the potential of rDV‐PIII‐silk as a biomimetic vascular graft material.
Publisher: Elsevier BV
Date: 09-2021
Publisher: American Chemical Society (ACS)
Date: 12-04-2021
Publisher: Wiley
Date: 23-04-2021
Abstract: Surface modification of biomaterials is a promising approach to control biofunctionality while retaining the bulk biomaterial properties. Perlecan is the major proteoglycan in the vascular basement membrane that supports low levels of platelet adhesion but not activation. Thus, perlecan is a promising bioactive for blood‐contacting applications. This study furthers the mechanistic understanding of platelet interactions with perlecan by establishing that platelets utilize domains III and V of the core protein for adhesion. Polyvinyl chloride (PVC) is functionalized with recombinant human perlecan domain V (rDV) to explore the effect of the tethering method on proteoglycan orientation and bioactivity. Tethering of rDV to PVC is achieved via either physisorption or covalent attachment via plasma immersion ion implantation (PIII) treatment. Both methods of rDV tethering reduce platelet adhesion and activation compared to the pristine PVC, however, the mechanisms are unique for each tethering method. Physisorption of rDV on PVC orientates the molecule to hinder access to the integrin‐binding region, which inhibits platelet adhesion. In contrast, PIII treatment orientates rDV to allow access to the integrin‐binding region, which is rendered antiadhesive to platelets via the glycosaminoglycan (GAG) chain. These effects demonstrate the potential of rDV biofunctionalization to modulate platelet interactions for blood contacting applications.
Publisher: Elsevier BV
Date: 03-2022
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0BM01010C
Abstract: Silk photo-lyogels fabricated by di-tyrosine photo-crosslinking and ice-templating silk fibroin on 3D printed templates toward in situ tissue engineering applications.
Publisher: American Chemical Society (ACS)
Date: 07-05-2018
Abstract: Silk fibroin isolated from Bombyx mori cocoons is a promising material for a range of biomedical applications, but it has no inherent cell-interactive domains, necessitating functionalization with bioactive molecules. Here we demonstrate significantly enhanced cell interactions with silk fibroin biomaterials in the absence of biofunctionalization following surface modification using plasma immersion ion implantation (PIII). Further, PIII treated silk fibroin biomaterials supported direct covalent immobilization of proteins on the material surface in the absence of chemical cross-linkers. Surface analysis after nitrogen plasma and PIII treatment at 20 kV revealed that the silk macromolecules are significantly fragmented, and at the higher fluences of implanted ions, surface carbonization was observed to depths corresponding to that of the ion penetration. Consistent with the activity of radicals created in the treated surface layer, oxidation was observed on contact with atmospheric oxygen and the PIII treated surfaces were capable of direct covalent immobilization of bioactive macromolecules. Changes in thickness, amide and nitrile groups, refractive index, and extinction coefficient in the wavelength range 400-1000 nm as a function of ion fluence are presented. Reactions responsible for the restructuring of the silk surface under ion beam treatment that facilitate covalent binding of proteins and a significant improvement in cell interactions on the modified surface are proposed.
Publisher: Portland Press Ltd.
Date: 08-09-2021
DOI: 10.1042/BST20210359
Abstract: The rising incidence of cardiovascular disease has increased the demand for small diameter (& mm) synthetic vascular grafts for use in bypass surgery. Clinically available synthetic grafts (polyethylene terephthalate and expanded polytetrafluorethylene) are incredibly strong, but also highly hydrophobic and inelastic, leading to high rates of failure when used for small diameter bypass. The poor clinical outcomes of commercial synthetic grafts in this setting have driven significant research in search of new materials that retain favourable mechanical properties but offer improved biocompatibility. Over the last several decades, silk fibroin derived from Bombyx mori silkworms has emerged as a promising biomaterial for use in vascular applications. Progress has been driven by advances in silk manufacturing practices which have allowed unprecedented control over silk strength, architecture, and the ensuing biological response. Silk can now be manufactured to mimic the mechanical properties of native arteries, rapidly recover the native endothelial cell layer lining vessels, and direct positive vascular remodelling through the regulation of local inflammatory responses. This review summarises the advances in silk purification, processing and functionalisation which have allowed the production of robust vascular grafts with promise for future clinical application.
Publisher: American Chemical Society (ACS)
Date: 27-08-2020
No related grants have been discovered for Kieran Lau.