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Bone & Joint Research
Vol. 11, Issue 11 | Pages 763 - 776
1 Nov 2022
Zhang Y Jiang B Zhang P Chiu SK Lee MH

Aims

Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders.

Methods

We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1PrαTACE’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 36 - 36
1 Aug 2012
Grange S Wills G Gilbert L Santer M Recio A Kanani M Zhang P Smitham P
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Background and objectives

The prevention of osteoporotic fractures is a global problem. Key to this strategy is efficient identification of ‘at risk’ patients in order to address the osteoporosis pandemic, including the identification of previously sustained fractures. GP practices are now integrating touch screens as a method of registering patients' attendance for an appointment, so all ages of patients are becoming familiar with this channel of communication. Our touch screen patient administered questionnaire system intends to provide an effective solution.

Methods

The Virtual Research Integration Collaboration (VRIC) framework supports the integration of basic science and clinical research. It enables the management of research lifecycles by integrating scientific approaches with everyday work practice in a virtual research environment (VRE). ‘Catch Before a Fall’ (CBaF) is a clinical research project using VRIC, using a dedicated interface, co-designed by orthopaedic surgeons and basic scientists, adapted for sensory and IT impaired subjects to capture such information, since approximately 75% of registered over 65 year olds visit their GP each year.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_III | Pages 248 - 248
1 Jul 2011
Padmos D Zhang P Dunbar MJ
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Purpose: Component loosening is a leading cause of joint replacement failure. Modifying titanium surfaces with chemically bound functional proteins, such as bone morphogenetic protein (BMP), can efficiently strengthen the interface between prosthesis and bone. A prototype system was developed by using gold nanoparticles (AuNPs) to bridge lysozyme (compositionally similar to BMP) and titanium.

Method: For reference, lysozyme-conjugated gold nanoparticles (Lys-AuNPs) were prepared in solution via two different pathways:

gold compound was reduced in the presence of lysozyme to form Lys-AuNPs or

citrate-stabilized AuNPs were functionalized with mercaptopropionic acid (MPA) to produce carboxylic acid terminated AuNPs which were mixed with lysozyme.

Both solutions were characterized with transmission electron microscopy, ultraviolet-visible spectroscopy, circular dichroism spectroscopy (CD), and enzymatic assays. Next, AuNPs were prepared on 99.5% titanium foil discs (n=32) through electroless deposition. Deposition parameters were modified to create two groups of discs with different average diameters of AuNPs, measured by scanning electron microscopy. Some discs from both groups also underwent treatment with MPA. All discs were treated with lysozyme and the adsorbed amounts and activities of lysozyme were examined with micro BCA and enzymatic assays.

Results: Lysozyme and AuNPs can be conjugated in solution via two different pathways. CD results showed a significant change in the secondary structure of the lysozyme and decrease in enzymatic activity when directly conjugated to AuNPs; however, little change in secondary structure and enzymatic activity was observed for the lysozyme with MPA functionalized AuNPs. For the AuNPs on the titanium discs, SEM showed that the two groups had significantly different average AuNP diameters. Bioactive lysozyme was immobilized onto the discs and the results suggested that discs with the largest AuNPs treated with MPA had higher adsorption and activity of lysozyme.

Conclusion: A wet-chemical technique may be used to bind lysozyme to titanium via gold nanoparticles. Additionally, it was possible to control the size of the AuNPs on titanium which provides a good platform for further functionalisation with thiol molecules such as MPA. This technique holds promise for binding more functional molecules to surgical implants, hence creating “smart” implants that react to their local environment.