Porosity control and influence in 3D bioprinted scaffolds

Header Image: Schematic representation of scaffolds characterized by three different lay-down patterns. (a) 0◦/90◦. (b) 0◦/60◦/120◦. (c) 0◦/45◦/90◦/135◦. [1]

The main objective of 3D bioprinting is to recreate human tissues with the same mechanical, structural and biological properties as the corresponding native tissue, in order to solve the problems associated with conventional transplantation techniques (donor site morbidity, organ shortage, etc.). For this purpose, different cell types combined with different biomaterials have been bioprinted according to specific models, but obtaining a 3D scaffold with the desired properties remains a challenge.

The advantage of 3D bioprinting over conventional scaffold fabrication techniques is the ability to control the 3D architecture of scaffolds through parameters such as pore size and geometry. Pore size and shape influence the resulting mechanical properties as well as cell behavior and tissue growth over time. Domingos et al. showed that for a lay down pattern of 0◦/90◦ (filament orientation between layers) with different pore sizes, poly(ε-caprolactone) scaffolds with smaller pores exhibit significantly higher stiffness under compressive conditions, which is an important property in applications such as bone tissue engineering. For different pore shapes with the following lay down pattern: 0◦/90◦, 0◦/60◦/120◦ and 0◦/45◦/90◦/135◦ (see figure) and the same porosity, the increasing number of angles between the filaments of the different layers leads to an increase in the deformability of the construct under compressive conditions.

Regarding the influence of architecture on cell behavior, viability and proliferation of human mesenchymal stem cells (hMSCs) were studied for 21 days and showed that larger pores with a lay down pattern of 0◦/90◦ improve viability and proliferation.

References

[1] Domingos, M., et al. “THE FIRST SYSTEMATIC ANALYSIS OF 3D RAPID PROTOTYPED POLY (e-CAPROLACTONE) SCAFFOLDS MANUFACTURED THROUGH BIOCELL PRINTING: EFFECT OF PORE SIZE AND GEOMETRY ON COMPRESSIVE MECHANICAL BEHAVIOR AND IN VITRO HMSC VIABILITY.” 1758-5082 5 (2013).

This article was written by Marie Moulin as part of an ongoing series of scientific communications written and curated by BioTrib’s Early Stage Researchers.

Marie is researching the Bioprinting of Bone and Cartilage at Uppsala University, Sweden.

Poly(electrolytes) applications for friction reduction

Header image: schematic of a polymer brush interface. 

Polyelectrolytes are charged polymers with special hydration properties. They are present in our bodies as sulfated glycosaminoglycans (e.g., chondroitin sulfate) and play an important role in lubrication and tissue homeostasis. Tissue engineering novelties are trying to bring the best out of the synthetic world, by mimicking the special properties of these electrolytes, grafted to all kinds of materials [1].

Kwon and Gong [2] studied the effect of negatively charged biomimetic polyelectrolytes for multiple applications, including low friction. Pavoor et al. [1] show the effects of the friction of grafting negatively poly(acrylic acid) and positively charged poly(allylamine hydrochloride) on ultra-high molecular weight polyethylene. Qin et al. [3] showed that the polydopamine-assisted immobilization of chitosan (net positive charge) can improve the biocompatibility and tribological properties of Cobalt Cromium implants. They demonstrated a tenfold decrease in the coefficient of friction upon brush-grafting.  

 

This article was written by André Plath as part of an ongoing series of scientific communications written and curated by BioTrib’s Early Stage Researchers.

André is researching Boundary Lubrication of Fibrous Scaffolds at ETH Zürich, Switzerland.

 

 

 

References

[1]          P.V. Pavoor, B.P. Gearing, O. Muratoglu, R.E. Cohen, A. Bellare, Wear reduction of orthopaedic bearing surfaces using polyelectrolyte multilayer nanocoatings, Biomaterials. 27 (2006) 1527–1533. https://doi.org/10.1016/j.biomaterials.2005.08.022.

[2]          H.J. Kwon, J.P. Gong, Negatively charged polyelectrolyte gels as bio-tissue model system and for biomedical application, Current Opinion in Colloid & Interface Science. 11 (2006) 345–350. https://doi.org/10.1016/j.cocis.2006.09.006.

[3]          L. Qin, H. Sun, M. Hafezi, Y. Zhang, Polydopamine-Assisted Immobilization of Chitosan Brushes on a Textured CoCrMo Alloy to Improve its Tribology and Biocompatibility, Materials. 12 (2019) 3014. https://doi.org/10.3390/ma12183014.    

Space and Medicine: an unexpected connection

So many lives have been saved thanks to the Hubble Telescope.

It sounds incredible but, among the tens of thousands of examples of technologies and their positive impacts on human lives, there is one story that reminds us how remarkable space exploration can be. An extraordinary story that begins with a colossal failure.

Mammography with arrows highlighting artefacts indicative of breast cancer

The image shows a mammography, and the arrows indicate microcalcifications, which are sometimes the telltale sign of breast cancer.

It was possible to detect those microcalcifications sharply because of the legendary Hubble telescope. You may be wondering how.

At the beginning of its usage, the first Hubble images were blurry because the primary mirror had been over-smoothed and flattened 2 thousandths of a millimeter too much. It is roughly one-fiftieth the thickness of a sheet of paper, yet thick enough to bounce the incident light slightly out of focus. Thus, various techniques were developed to increase the dynamic range and spatial resolution of Hubble’s initially blurred images before detecting the true cause and repairing it.

These techniques had also been applied to medicine and, in this case, allowed doctors to detect calcifications in the female breast that were smaller than before and would otherwise have gone undetected, resulting in earlier diagnosis and treatment, which is critical as the earlier the cancer is detected and treated, the greater the chances of a patient making a full recovery.

This is only one of many, many, endless instances of how space research can improve our lives.

Furthermore, this is an excellent example of how, even when a project appears to fall short of its goals or is deemed a failure, the spillover effects on the daily lives of human beings can be enormous.

This article was written by Elisa Bissacco as part of an ongoing series of scientific communications written and curated by BioTrib’s Early Stage Researchers.

She is studying a PhD in Tribological Characteristics of Nanofibrous Electrospun Materials at ETH Zurich.

Ben Clegg – Best Oral Presentation Prize

A few weeks ago I had the pleasure of presenting and attending at the conference for the Swedish Society of Biomechanics in Stockholm.

This was my first networking event outside the BioTrib consortium, so it was a great chance and experience to meet fellow colleagues working in the medical engineering field. The first day was a PhD and Post doctoral event enabling us to meet and chat with present and future associates. The following two days composed of engaging presentations and posters.

And I am honoured to have received the award for the prize of Best Oral Presentation! Titled: Biocompatibilty of 3D printed Polymers for use in total joint replacements.

I am looking forward to future conferences and networking events to present my forthcoming work and meet up with new friends and collaborators. I would like to thank Luleå University of Technology, the BioTrib consortium and Professor Nazanin Emami for providing me with the platform and opportunity to present my work and help promote myself in the field of Medical Engineering.

I thank you for taking the time to read this

Ben Clegg

This article was written by Ben Clegg part of an ongoing series of scientific communications written and curated by BioTrib’s Early Stage Researchers.

Ben is researching the Wear particle characterization and bio-compatibility of newly 3D printed self-lubricating polymer composites in total joint replacements at Luleå University of Technology, Sweden.

EFORT 2022

The European Federation of National Associations of Orthopaedics and Traumatology (EFORT) recently hosted its 23rd Congress in Lisbon, Portugal. This years main theme was Modern Patient Needs – Challenges and Solutions In Orthopaedics and Trauma.

PhD student Rob Elkington along with NU-SPINE Early Stage Researchers Beril Yenigul and Kaushikk Iyer all attended to present their orthopaedic biotribology projects to one of Europes largest meetings of knee, hip, and spine surgeons and researchers.

Kaushikk Iyer presented his ongoing research work which demonstrates the development of a novel portable benchtop setup that act as a representative to an orthopaedic joint wear simulator used as a pre-clinical evaluation tool for the testing of spine, hip and knee prostheses. Using Hardware-in-the-Loop (HiL) simulation, advanced control algorithms can be designed and tested rigorously and rapidly on the setup before its deployment into the joint wear simulator to test profiles of ISO standards and beyond that represent daily-living activities of patients.

Rob Elkington presented his poster on ‘Biomimetic PEEK Surfaces For Cartilage Preserving Focal Resurfacing’ which employs novel highly lubricious polymer brush systems optimised to interface with cartilage and preserve healthy tissue for minimally invasive focal cartilage repairs and hemiarthroplasty to delay and mitigate the need for total joint replacements.

Beril presented her poster on the ‘Design of Facet Joint Resurfacing Bearings for Tribological Testing Purposes’ which showcases a new paradigm in preclinical testing for facet joint implants in a custom built simulator.

Header Image: Kaushikk Iyer, Rob Elkington, Beril Yenigul who are all studying PhDs in Medical Engineering at the University of Leeds.

Super Innovation in Uppsala

Uppsala University and its Innovation hub have an enviable record of translating high-end science and engineering to the wider sector, with a few examples of this excellence provided here. The Uppsala Innovation Centre has been ranked in the global top five and has an extensive list of business start ups.

This article explains the role and services provide by Uppsala University Innovation and the support provided to students and researchers.  Importantly, the advisors have industrial experience which allows them to truly span the divide between academia and the commercial sector and can better identify the barriers and opportunities for the transfer of knowledge between sectors. 

Prof Cecilia Persson

Prof Cecilia Persson at Uppsala University, a BioTrib scientist in charge, has worked with Uppsala Innovation and the Innovation Centre closely, developing her new bone cement which will reduce the adverse effects of the current generation of injectables used to treat spinal fractures.

Controlling wear

Demand for total joint replacements in the UK continues to soar, driven by an aging population and an increasing number of younger patients undergoing these procedures.

Total knee replacement (TKR) operations are one of the most common surgical procedures globally with 2.6 million performed each year. Components have a limited life of approximately 15 years and in some cases earlier than expected replacement is required due to excessive wear. There are also additional serious concerns as wear debris can cause adverse reactions such as osteolysis, and soft tissue lesions.  The increasing implant rates and the burgeoning healthcare costs emphasize the need for research to improve implant function and longevity to avoid the need for expensive revision surgeries.

Video highlighting the wear mechanisms of all additively manufactured specimen types

Wear control, which relies on understanding the mechanisms of wear, is crucial in preserving the life of mechanical components and reducing costs. Additive manufacturing (AM) techniques can produce parts with tailored microstructure, however, little has been done to understand how this impacts the mechanisms of wear. In this paper Dr Myant and colleagues study the impact build orientation can have on initial grain arrangement and crystal orientation on the wear mechanisms of austenitic stainless steel in dry sliding contact.

Read more: Bahshwan, M., Myant, C. W., Reddyhoff, T., & Pham, M. S. (2020). The role of microstructure on wear mechanisms and anisotropy of additively manufactured 316L stainless steel in dry slidingMaterials & Design196, 109076.

Header figure: Graphical abstract of the Bahshwan research paper.

Transient mixed lubrication model of the human knee implant

Fantastic paper (Transient mixed lubrication model of the human knee implant) from Rob Hewson’s Group at Imperial outlining a computational approach to implant design in terms of the biotribology of knee replacements. Crucially, the investigation uses real-world implant geometries and a statistical description of the surface roughness. Interestingly the model predicts that, under the motion and loading cycles from the standard ISO 14243-3, the implant can demonstrate elastohydrodynamic, mixed and boundary lubrication.

Pressure distribution (in MPa) mapped onto the tibial insert at (a) 2% of the ISO gait cycle, (b) 48% of the ISO gait cycle, (c) 84% of the ISO gait cycle.

The paper was published in a special issue of the Journal ‘Biosurface and Biotribology’ in celebration of the life of Prof Duncan Dowson who, more than anyone, made an outstanding contribution to Biotribology especially from a Leeds perspective.

Image from Butt, H, Nissim, L, Gao, L et al. (3 more authors) (2021) Transient mixed lubrication model of the human knee implant. Biosurface and Biotribology. ISSN 2405-4518

Women living with HIV – carrying the burden of the pandemic.

Source: Sophia Forum – We are still here – accessed 25-10-21

All groups affected by HIV should have access to appropriate care and the opportunity to, for instance, enter clinical trials and access innovative treatments. A recent editorial noted the mismatch between those PLWH that were recruited to clinical trials (overrepresentation of young white males) and those seen in the general population (a more heterogeneric demography). Women have been severely underrepresented in many areas of HIV treatment and care including inclusion in research. This appears to be an ongoing issue across the HIV landscape with alternative approaches required to allow both access and opportunity in advancing care and its underpinning research. This is essential as in the UK a third of people living with HIV are women and globally the figure stands at fifty percent and it is incumbent on everyone that the right interventions are utilised in this as well as any other community. This is particularly important where intersectional issues make marginalisation and stigma even more challenging.  The near-invisibility of WLWH is not a recent phenomenon but one that has existed from the early 80s when HIV came to the fore and the public’s attention.  This is one legacy that the community needs to overcome and as Jacqui Stevenson says:

No more excuses: Making HIV research work for women. (Sophia Forum)

Other marginalised groups such as those from BAME backgrounds, whilst being disproportionately affected, were also largely excluded from trials and medical care more generally.

As ART has produced improved outcomes in terms of life expectancy, the demographics of people living with HIV has changed radically. A significant number of PLWH including women have a life expectancy similar to that found in the general population.  However, there are disparities between groups (see, for instance, Solomon et al 2020) and a general reduction in quality of life for PLWH due to the onset of a range of geriatric syndromes a decade or more earlier with ongoing discrimination. This has been emphasised recently by ongoing research and advocacy by Jacqui Stevenson who has studied WLWH growing older. The outcomes of the research provide eight asks to improve the lives of WLWH.

Advice for women and HIV including using PrEP can be found at:

Validation and Verification

Collectively, verification and validation are a cornerstone of many areas of research, none more so that in engineering and the physical sciences. Yet many early stage researchers have yet to appreciate their definitions or fully understand the signficance of these activities.  William Morales’, blog provides a brief introduction to Device Design Verification and Validation – useful for those just beginning in their careers in the MedTech arena or indeed anyone who needs a quick refresher.  However, there is still of lot of discussion about the use of the terms particulary between fields as there maybe nuances or historical context that means the defintions deviate – for instance the article at ResearchGate by Ryan and Wheatcroft (2017).  Simple defintions may employ something along the lines of:

  • verification - am I building something right
  • validation - am I building the right something

Software engineering, an increasingly important aspect of medical devices, especially through the rise of in situ/in vivo monitoring, has it owns definitions. Sargent defines the processes by which a researcher can V&V computational simulations whilst Viceconti et al (2021) discuss V&V for in silico trials.

Excellent paper from the Nu-Spine ETN – Congratulations to Seung and co-authors!

Seung Hun Lee and colleagues at ETH Zurich have recently published a peer reviewed paper “Comprehensive in vitro Comparison of Cellular and Osteogenic Response to Alternative Biomaterials for Spinal Implants” in Materials Science and Engineering: C. The article explored the effects of silicon nitride (SN) in terms of cell proliferation, mineralization and osteogenesis, all of which were deemed positive with respect to the effects of other materials including Ti and PEEK. A similar result to that of SiN was found for zirconia toughened alumina. Further, the paper demonstrates the potential of surface texturing in enhancing the osteogenic capacity of this material. The graphical abstract for the paper can be found below.

CC License – NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0).
Seunghun S. Lee, Stephanie Huber, Stephen J. Ferguson,
Comprehensive in vitro comparison of cellular and osteogenic response to alternative biomaterials for spinal implants,
Materials Science and Engineering: C, Volume 127, 2021, 112251, ISSN 0928-4931, https://doi.org/10.1016/j.msec.2021.112251.

BioTrib’s first ESR – Pedro Lima Dos Santos

A big welcome to Pedro from Campina Grande in Brasil.

Some of you will have met Pedro already through the on-line courses etc we have held previously. Just to let you know that Pedro has now been in the UK for 2 weeks of which 10 days were spent quarantining. Previously he had been working as a researcher in Lisbon, Portugal.  Like England in the UEFA final, Brasil lost 1-0 in the Copas America final vs Argentina over the weekend and on home territory so he is probably in need of some sympathy!

Pedro will be researching surface modifications in additive manufacturing processes to enhance artificial joint performance.

Surface Modifications of Breast Implants affect Immune Response.

Further evidence of the important effect of engineered surfaces on immune response, this time in breast implants. Such research demonstrates the importance of modifying the surface texture in a manner that reduces the foreign body response. These and other examples pave the way for the development of new technologies for enhancing a favourable response to the implant and reduce complications including, potential, arising from infection and surface contraction.

The authors of the original paper have already provided a classification system for functional biocompatibility with regard to surface roughness (see figure below).


Figure reproduced from: Barr et al, Journal of the Mechanical Behavior of Biomedical Materials, Volume 75, November 2017, Pages 75-81.  Attribution 4.0 International (CC BY 4.0)

EU offers Global opportunities to Postdoctoral researchers

The EU’s Horizon Europe has begun and Sweden, Switzerland and UK, as an associate partner that has the same rights as full partners, will be actively engaged in research. As such we will be submitting grants in areas of medical engineering and biomechanics using both bottom-up instruments and top-down specified calls.

One of these instruments that allows collaboration development are through the Postdoctoral fellowships – which allow an overseas post PhD researcher to undertake research and research training in Europe (max 8 years research experience since their PhD).  The proposed call opens on 18 May 2021 with a proposed call deadline 15 September 2021 (tbc). These fellowships provide a substantial salary as well as a research support allocation managed by the host institution.

The consortium members, University of Leeds, Uppsala University, Lulea Technical University, ETH Zurich and Imperial College London,  have considerable experience of hosting and developing the types of fellowships providing an open and innovative environment for the Fellows to develop. The consortium have considerable EU experience through both large scale programmes (lifeLongJoints.eu), mentoring EU fellows and a number of MSCA ITNs (now called doctoral networks) and would welcome discussions developing EU postdoctoral fellowship proposals. If you have any students who may be considering a postdoctoral research position and might be interested in med-tech/biomechanics then perhaps we can chat about this.  These fellowships are useful for answering research questions that both the beneficiary and the researcher are interested in.

Research – Inspiring paper from the Leeds-Imperial Group on the Fabrication of Cartilage-Inspired Hydrogel Entangled Polymer–Elastomer Structures.

Significant paper developing and modelling hydrogels with a goal of more closely representing those of cartilage. The material shows a similar equilibrium compressive modulus to that observed in cartilage and allows for both rehydration and poroelastic lubrication mechanisms. BioTrib looks forward to seeing further work from this partnership of leading tribological and modelling groups.

Abstract Image

Figure – Reprinted with permission from: Fabrication of Cartilage-Inspired Hydrogel/Entangled Polymer–Elastomer Structures Possessing Poro-Elastic Properties, Siavash Soltanahmadi, Nicholas Raske, Gregory N. de Boer, et al.  ACS Applied Polymer Materials, Copyright 2021 American Chemical Society