Biomimetics and Biomimicry in Engineering

Posts Tagged ‘Healthcare’

A Titanium-Palladium device to enable the catalytic transformation from a prodrug to an active anticancer drug

In Publications on 2019/02/17 at 12:54 pm

Our last paper on the metallurgy of Titanium with a transition metal coating, Palladium, to enable the bioorthogonal chemistry and activate an anticancer prodrug has been published here. It has been the fruits of a collaboration with the BOOM Chemistry Lab at the Edinburgh Cancer Research UK, MRC IGMM, University of Edinburgh.

The survival of people diagnosed with cancer will improve with advances in therapies and the availability of different routes that can be supplementary or even replacements for more aggressive therapies, e.g. chemotherapies that are limited by a lack of selectivity and unwanted side effects. In this paper we propose the initial steps towards a paradigm shift in cancer treatment through the in-situ drug activation and delivery of anti-tumour drugs, applied locally and directly to the cancerous region to minimise those side effects of the more traditional therapies.

To harness the potential of the metal/prodrug interface bio-orthogonal organometallic chemistry, we have developed novel Pd-loaded titanium carriers capable of mediating the spatiotemporal generation of toxic drugs from an inactive precursor (i.e. the prodrug). We have demonstrated this bio-orthogonal activation in lung cell culture conditions, since lung cancer is one of the most prevalent forms of cancer worldwide.

Zoom: 1x / Objective: Epi-plan 5x/0,13 / MicroscopeName: F92129

Surface of the Titanium carrier prepared for this application

This experimental study demonstrates how an optimised manufacturing protocol to produce a scaffold can turn it into a therapeutic device through its “switchable” chemistry, and this represents and exciting route towards novel targeted, personalised, tumour-shrinking, cancer treatment therapies.

The paper ‘Design and manufacture of functional catalyst-carrier structures for the bioorthogonal activation of anticancer agents‘ has been published in the New Journal of Chemistry, 2019, 43, 1449 – 1458 DOI: 10.1039/C8NJ05704D

If you would like a free copy of the paper, use this link: here

Manuscript ID: C8NJ05704D, Password: 975964 (get it now! this link will expire on 15th March)

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A manufacturing protocol for the production of biocompatible porous catalysts

In Publications, Seminars and Keynotes on 2018/02/09 at 2:23 pm

Mohammad Alqahtani, researcher of the Multifunctional Materials Lab, is conducting research to develop a new manufacturing method and testing protocol for the fabrication of biocompatible catalyst-carrier for controlled drug delivery. The carrier could be used as a prodrug activation agent when implanted in cancerous tissues in the human body. When orally-ingested drugs are deployed into the area under treatment through the blood stream, the catalyst could activate the prodrugs and these affect the area by releasing anticancer treatment. In this research, a titanium-based carrier was used to manufacture the medical device due to their biocompatibility and non cytotoxicity.

In a feasibility study, the samples were made as porous carriers.  Porous materials have larger surface area than solid materials. Therefore, when the contact area between the drug and the carrier increases this has a potency effect on the effectiveness of the drug.

His work has been presented recently

20170608_ma_poster-wolfsonconf1.jpg

This work is a continuation of the research work already presented here and published here and here.

Mechanical behaviour that mimics that of cortical and trabecular bones

In Publications on 2017/11/30 at 11:22 am

We have published our most recent results on how porosity and pore size affect both mechanical properties and biological response of osteoblastic cells on titanium porous structures.

Working with volumetric porosities that match those of cortical and trabecular bone, we finely controlled the pore size in the substrate with the aim to assess how a variation in pore size can tailor mechanical properties (i.e. stiffness and strength). Furthermore, we report how we could establish regressions that would allow us to create a design tool based on porosity, so it would return the desired mechanical properties values.

From a bioengineering viewpoint, the results from this study showed that scaffolds with the lowest pore range (45-106um) presented the largest number of cells attached in the early days  (day 1 and  3) indicating this microarchitecture was the best indicated for cell attachment. Pore range >300 mm exhibited the most favourable conditions for cell proliferation, surpassing those on the control samples. The viability of scaffolds with pore size 212-300um was the poorest, indicating these scaffolds do not promote cell proliferation for osteosarcoma osteoblasts due to the distance the cells had to span.

Proliferation_supplementary

Proliferation data from the osteoblasts on titanium porous (A,B 1-4) and non-porous (Ti) normalised to the previous timepoint of culture (in/in-1, n=3, 7, 12); as it appears in https://www.ncbi.nlm.nih.gov/pubmed/28532024

The study can be found here in the Materials Science and Engineering C: Materials for Biological Applications.

Engineered foams for wheelchair seating

In Publications on 2017/11/08 at 10:39 am

We have published the results arising from our studies on open cell polymeric foams that can be tailored so that they support those who are bed bound or wheelchair users providing them with general well being and alleviating pressure points.

Avoiding pressure points, managing sores and permitting air permeability are the three main design specifications that clinicians aim to when choosing a cushion. In addition to that, a functional cushion, such as those who support lateral movements (e.g. leaning sideways to grab a glass of water and be helped to return to your initial position without compromising one’s stability) and protect from vibration and impacts (e.g. dropping off a curb), are the focus of our research project.

The Multifunctional Materials Lab and clinicians from the NHS have studied how we can help their clinician colleagues understand cushion performance and therefore aid them with the prescription of these to patients and users.

The results from our study have been published in the Medical Engineering and Physics Journal and in the Assistive Technology Journal .

The International Standard that regulates developments in this topic is the ISO16840-2:2007, which is currently under revision. We are hoping our work to inform their work and assist in their revisions for the replacement ISO 16840-2.

iso_replacement

 

Porosity and pore size effect on the properties of sintered Ti35Nb4Sn alloy scaffolds and their suitability for tissue engineering applications

In Publications on 2017/11/03 at 11:04 am

Our most recent results on the importance of tailoring porosity engineered materials for cell regeneration are to be published in the Journal of Alloys and Compounds.

Porous scaffolds manufactured via powder metallurgy and sintering were designed for their structure (i.e. pore size and porosity) and mechanical properties (stiffness, strength) to be controlled and tailored to mimic those of human bone. The scaffolds were realised to fulfill three main objectives:

(i) to obtain values of stiffness and strength similar to those of trabecular (or spongy) bone, with a view of exploiting these as bone grafts that permit cell regeneration,

(ii) to establish a relationship between stiffness, strength and density that allows tailoring for mass customisation to suit patient’s needs; and

(iii) to assess alloy cytotoxicity and biocompatibility via in vitro studies.

The results obtained using a very low stiffness alloy (Ti35Nb4Sn) further lowered with the introduction of nominal porosity (30–70%) with pores in the ranges 180–300 μm and 300–500 μm showed compatibility for anatomical locations typically subjected to implantation and bone grafting (femoral head and proximal tibia). The regression fitting parameters for the linear and power law regressions were similar to those found for bone specimens, confirming a structure favourable to capillary network formation. Biological tests confirmed non-cytotoxicity of the alloy.

Scaffolds of porosity nominal 50%vol and pore range 300–500 μm performed best in the adhesion and propagation assays due to a good balance between surface area and pore cavity volume.

Graphical abstract for https://doi.org/10.1016/j.jallcom.2017.10.026

Study on bio-mechanical properties of porosity scaffolds tailored for cell regeneration, https://doi.org/10.1016/j.jallcom.2017.10.026

A pre-view of the article appears on Journal of Alloys and Compounds, Volume 731, 15 January 2018, Pages 189-199, https://doi.org/10.1016/j.jallcom.2017.10.026.

 

The effect of pore size and porosity on mechanical properties and biological response of porous titanium scaffolds

In Publications on 2017/10/27 at 8:49 am

The Multifunctional Materials Lab has recently published our results on porosity tailored titanium scaffolds. The results were very interesting and demonstrated there is more to what the eye can see in a first pass: cells are extremely sensitive to cavities and ‘think’ about whether they should bridge a gap or simply fill the hole.

Our article can be found here

The effect of pore size and porosity on elastic modulus, strength, cell attachment and cell proliferation was studied for Ti porous scaffolds manufactured via powder metallurgy and sintering. Porous scaffolds were prepared in two ranges of porosities so that their mechanical properties could mimic those of cortical and trabecular bone respectively. Space-holder engineered pore size distributions were carefully determined to study the impact that small changes in pore size may have on mechanical and biological behaviour. The Young’s moduli and compressive strengths were correlated with the relative porosity. Linear, power and exponential regressions were studied to confirm the predictability in the characterisation of the manufactured scaffolds and therefore establish them as a design tool for customisation of devices to suit patients’ needs. The correlations were stronger for the linear and the power law regressions and poor for the exponential regressions. The optimal pore microarchitecture (i.e. pore size and porosity) for scaffolds to be used in bone grafting for cortical bone was set to < 212 μm with volumetric porosity values of 27–37%, and for trabecular tissues to 300–500 μm with volumetric porosity values of 54–58%. The pore size range 212–300 μm with volumetric porosity values of 38–56% was reported as the least favourable to cell proliferation in the longitudinal study of 12 days of incubation.

https://doi.org/10.1016/j.msec.2017.03.249

Cells are sensitive to small changes in pore size and some are even detrimental to their proliferation. https://doi.org/10.1016/j.msec.2017.03.249

Published in Materials Science and Engineering: C, Volume 77, 1 August 2017, Pages 219-228, https://doi.org/10.1016/j.msec.2017.03.249

Congratulations to Fares!

In Info on 2017/04/11 at 6:57 pm

My PhD student Fares Almushref successfully defended his PhD thesis entitled ‘Design and manufacture of engineered titanium-based materials for biomedical applications’.

Congratulations to him for the hard work for the last 3 years and the great effort to get it finished in time for the summer graduation.

Fares

Applying International Standards to manage comfort

In Publications on 2017/03/01 at 6:46 pm

Have you ever seen the seat testing device at IKEA? We have used a very similar one in our study.

ikea_durability_test

IKEA durability test

Open cell polymeric foams can be tailored so that the support provided and the level of stability is customised to people’s needs. For those who are bed bound or wheelchair users the selection of a cushion can improve their health and general well being. Avoiding pressure points, managing sores and permitting air permeability are the three main design specifications that patients and clinicians aim to when choosing a cushion. In addition to that, a functional cushion, such as those who support lateral movements (e.g. leaning sideways to grab a glass of water and be helped to return to your initial position without compromising one’s stability) and protect from vibration and impacts (e.g. dropping off a curb), are the focus of our last research project.

My team and I have had the privilege to work with the biomechanics and physiotherapists at the SMART Centre at Astley Ainslie Hospital in Edinburgh to study how we can help their clinician colleagues understand cushion performance and therefore aid them with the prescription of these to patients and users.

The results from our study have been presented at the PMG 2012 Conference and recently published by the Assistive Technology journal (free e-prints can be collected here). This has allowed us to interact with the community that is preparing the new version of the ISO16840-2:2007 which will regulate developments in this area.

 

Assisting mums-to-be in water and house births

In Info on 2014/06/12 at 7:05 pm

The medical device we designed to help midwives monitor labour with minimum interruption has seen the light! Different newspapers and media have been attracted to our invention, a team effort from our colleagues in Univ of Edinburgh and NHS, Heriot-Watt University, and us in Loughborough.

This has been a great enterprising opportunity for us. Being able to form a team with engineers, designers, medics and business developers has been truly rewarding. We all showed great enthusiasm and reached out to understand each others’ ‘language’ so we could bring the project to a fruitful completion. Working with midwives for the development of a new medical device was great because they were able to provide us with insightful input during the design stages, and with useful feedback in the development phase.  We hope the device will help the midwives carry out their work in more comfortable conditions, and for future mothers-to-be to benefit from this device that allows them to experience a more dignifying labour.

The work has been presented at the Perinatal Medicine 2014 (Harrogate International Centre, Monday 9th – Wednesday 11th June 2014).

The press releases can be found here and here

More press material can be found here and here and here.

Engineered metal implants to target cancer cells and eradicate side effects of chemotheraphy

In Publications on 2014/03/06 at 12:12 am

The work done by my colleague Dr Asier Unciti-Broceta and our ‘dream team’ has been published in Nature Communications.

Asier proudly presents to the world the work done using his clever “bioorthogonal” method for activating a prodrug by palladium catalyzed dealkylation. What motivates us is to move towards the eradication of the side effects of chemotheraphy (e.g. depleted immune system, hair loss, tiredness, etc) in the very near future. This is done by focusing the cancer treatment only to the affected area. Like a ‘trojan horse’, in our vision we implant the engineered catalyst carrier first. Then, by a selective activation via oral drugs, we produce the chemo-destructive effect with maximum effect on the targeted area, and minimal negative effects (i.e. death) on healthy tissue.

The technology in a 'nutshell'

The technology in a ‘nutshell’

The full paper can be found here.

The press release by University of Edinburgh can be viewed here.

Asier is an academic fellow at the Edinburgh Cancer Research UK Centre at the MRC Institute of Genetics and Molecular Medicine, the University of Edinburgh.