Cartilage Tissue Engineering and Electrospinning

Cartilage-related diseases are a promising field to explore in tissue engineering and regenerative medicine. The cartilage hydrated structure is aneural, avascular, and non-lymphatic, which complicates natural regeneration [1,2]. The increase in life expectancy and obesity is directly correlated to osteoarthritis –the disease caused by the degradation of cartilage. The painful consequences also increase comorbidities and burden patients and healthcare providers with exorbitant costs [3,4].

Currently, surgical and non-surgical therapies are employed to address osteoarthritis. They are not permanent solutions [5–7]. Therefore, several groups are developing hydrogels [8,9], electrospun mats [10], and other biomaterials to mimic the natural properties of cartilage. These implants can increase patients’ quality of life, reducing pain, comorbidities, and other undesirable effects after their clinical trials and regulatory agency approval.

 

Chondrocyte proliferation on neutralized chitosan fiber mats. Image adapted from https://doi.org/10.1016/j.fhfh.2021.100018 under Creative Commons License

Yilmaz and Zeugolis discuss the promises, challenges, and future perspectives of electrospinning applied to cartilage tissue engineering [11]. They emphasize that although electrospinning literature is abundant in the Pubmed database, few studies explore electrospining’s potential applied to cartilage tissue engineering. The authors demonstrate with pre-clinical results that stem cell-seeded electrospun scaffolds combined with other techniques (3D printing and freeze-drying) can recover lubricating properties, mechanical resistance and restore cartilage tissue properties [11]. Although the reviewed studies consider small animals (rats, mice, and rabbits), they are promising to people suffering from the pain and harmful effects of osteoarthritis worldwide [11].

 

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.

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[1]        L.M. Billesberger, K.M. Fisher, Y.J. Qadri, R.L. Boortz-Marx, Procedural Treatments for Knee Osteoarthritis: A Review of Current Injectable Therapies, Pain Res. Manag. 2020 (2020) 1–11. https://doi.org/10.1155/2020/3873098.

[2]        E.D. Bonnevie, V.J. Baro, L. Wang, D.L. Burris, Fluid load support during localized indentation of cartilage with a spherical probe, J. Biomech. 45 (2012) 1036–1041. https://doi.org/10.1016/j.jbiomech.2011.12.019.

[3]        S. Glyn-Jones, A.J.R. Palmer, R. Agricola, A.J. Price, T.L. Vincent, H. Weinans, A.J. Carr, Osteoarthritis, in: Lancet, Lancet Publishing Group, 2015: pp. 376–387. https://doi.org/10.1016/S0140-6736(14)60802-3.

[4]        D.J. Hunter, L. March, M. Chew, Osteoarthritis in 2020 and beyond: a Lancet Commission, Lancet. 396 (2020) 1711–1712. https://doi.org/10.1016/S0140-6736(20)32230-3.

[5]        Y. Lee, J. Choi, N.S. Hwang, Regulation of lubricin for functional cartilage tissue regeneration: a review, Biomater. Res. 22 (2018) 9. https://doi.org/10.1186/s40824-018-0118-x.

[6]        G. Musumeci, C. Loreto, M.L. Carnazza, F. Coppolino, V. Cardile, R. Leonardi, Lubricin is expressed in chondrocytes derived from osteoarthritic cartilage encapsulated in poly(ethylene glycol) diacrylate scaffold, Eur. J. Histochem. 55 (2011) 31. https://doi.org/10.4081/ejh.2011.e31.

[7]        W. Kabir, C. Di Bella, I. Jo, D. Gould, P.F.M. Choong, Human Stem Cell Based Tissue Engineering for In Vivo Cartilage Repair: A Systematic Review, Tissue Eng. Part B Rev. 27 (2021). https://doi.org/10.1089/ten.teb.2020.0155.

[8]        Y. Gombert, R. Simič, F. Roncoroni, M. Dübner, T. Geue, N.D. Spencer, Structuring Hydrogel Surfaces for Tribology, Adv. Mater. Interfaces. 6 (2019) 1901320. https://doi.org/10.1002/admi.201901320.

[9]        M. Jurak, A.E. Wiącek, A. Ładniak, K. Przykaza, K. Szafran, What affects the biocompatibility of polymers?, Adv. Colloid Interface Sci. 294 (2021) 102451. https://doi.org/10.1016/j.cis.2021.102451.

[10]      J.K. Wise, A.L. Yarin, C.M. Megaridis, M. Cho, Chondrogenic Differentiation of Human Mesenchymal Stem Cells on Oriented Nanofibrous Scaffolds: Engineering the Superficial Zone of Articular Cartilage, Tissue Eng. Part A. 15 (2009) 913–921. https://doi.org/10.1089/ten.tea.2008.0109.

[11]      E.N. Yilmaz, D.I. Zeugolis, Electrospun Polymers in Cartilage Engineering—State of Play, Front. Bioeng. Biotechnol. 8 (2020). https://doi.org/10.3389/fbioe.2020.00077.

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.

Interesting paper that investigates corrosion and tribocorrosion behavior of binary and ternary carbide coatings for load-bearing implants

An exciting paper discussing the feasibility of binary and ternary carbide coatings for load-bearing implants with improved biocompatibility was published by Pana and co-workers in 2020. The peer-reviewed article was published in the Coatings journal and it is titled “In vitro corrosion and tribocorrosion performance of biocompatible carbide coatings”.

This work assessed elemental and phase composition, tribo-mechanical properties, corrosion and tribocorrosion of coatings deposited by cathodic arc evaporation on polished 316L SS discs (Ra = 50 ± 2 nm). TiNbC coating outperformed the other synthesized coatings in terms of initial surface roughness and corrosion resistance (shown by the lowest change in Ra before and after corrosion tests). Even though ZrC and TiNbC displayed similar polished wear tracks, the latter exhibited the lowest friction coefficient and wear rate on the tribocorrosion tests.

These results delivery an important advancement towards the development of coatings more biocompatible, presenting higher corrosion resistance along with improved tribocorrosion performance. The graphical abstract shown below showcases some of the results of this worth reading paper.

 

CC License – 4.0 International (CC BY 4.0) Pana, I.; Vladescu, A.; Constantin, L.R.; Sandu, I.G.; Dinu, M.; Cotrut, C.M. In Vitro Corrosion and Tribocorrosion Performance of Biocompatible Carbide Coatings. Coatings 2020, 10, 654. https://doi.org/10.3390/coatings10070654

 

This post was written by Pedro Luiz Lima dos Santos as part of an ongoing series of scientific communications written and curated by BioTrib’s Early Stage Researchers.

Pedro is researching the Functional Biotribology of the Surface Engineering of 3D Printed Components at the University of Leeds, UK.

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.

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)

10,000 and counting – Congratulations to the ERC for reaching this impressive milestone!

The European Research Council has just awarded its 10,000th grant!  The award was an Consolidator Grant provided to Professor Inga Berre of the University of Bergen – congratulations! Not sure it is a milestone under the definition provided by the online manual for Horizon Europe, but BioTrib is not going to allow this to stop celebrating another EU Horizon success – champers out folks! To celebrate this fantastic achievement the ERC had a celebration attended by Senior EU dignitaries as well previous award winners outlining the support and subsequent impact such an award had on their careers and the wider community.

 

 

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

 

Training – What skills does a PhD student need for a successful career outside academia?

Melina Papalampropoulou-Tsiridou has recently written an interesting blog on the PLOS ECR community pages which poses the following question:

PhD training in the 21st century: is there something missing?

This is a difficult question with the myriad of skills required in differing jobs across the STEM sector, from a science policy adviser to a postdoctoral researcher in a laboratory at a prestigious global University.  Indeed some of the skills required of a PhD student in industry may be become less important than they were in actually doing the PhD, whilst others will come to the fore once in paid employment post PhD.  An example, may be the focus on the idea of being an independent researcher, a student pursuing their own research goals, sometimes linked to other projects as in ETNs, sometimes not.  However, in industry, or even in EU funded large scale projects such as LifeLongJoints, the research is often completed in teams with groups of people explicitly working towards a common goal.  In it is not to say that PhDs are not highly prized, they are! Employers seek researchers with skills in critical analysis, a greater degree of objectivity and adept at generating new ideas. It is to be remembered that most PhDs will end up outside the academic sector.  In a recent BioTrib meeting with industry on supervisory training it was suggested that PhD candidates lack Project Management and other organisational skills when entering industry, but that the core creativity was highly valued. Melina provides similar examples around Networking and Management skills which appears to reflect a wider observation.  In BioTrib the Early Stage Researchers will undertake some Research Management training including Project Management, Ethics and aspects of Regulation. However, more can be done to make this more effective and embed this within European Research (Training) Programmes without impacting on the valuable core research that these ESRs do whilst undertaking a PhD.

If you want to outline what skills you think are missing in a PhD programme, please contact us here at BioTrib.

Armageddon… not quite but why don’t they stick scales on their photos!

Exciting news reported in the local papers in Gloucestershire as well as news nationally in the UK this week, as small meteorite hit the UK. First signs were a bright, extended meteor track shot on various door bell and security cameras, with a subsequent find by a bemused family on their driveway.  The family then alerted the experts (don’t tell Gove) who now reliably tell us it contains material from the beginning of the solar system.  Indeed one could argue that the material was probably from the Big Bang in one form or another, but that discussion is for another day.  But BBC and other media providers, please put a scale bar on your pics when there is no natural reference.  The meteorite itself could be any size and the picture of the drive could easily be of a coating on a metals surface of the order of a few microns or less or a stony desert!  Admittedly, if the latter were true the resulting impact would bring out more than a few avid meteorite hunters.

May this be a lesson for budding coating engineers – you don’t want your rather novel coating that is about to revolutionise joint replacement to be mistaken for a meteorite impact!

Health – COVID fightback: the critical role of HIV experts

An article in the Guardian highlights the critical skills needed to identify, treat and limit the impact of new diseases.  It is important these and other skills are retained as the global community moves forward in what may become a continuous battle for health security. The broader inputs from behavioural scientists and other stakeholders/participants in the social science field are equally important in our fight against current and emerging disease states as interventions depend on the public perception of risk and how this plays out in the community. This crucial piece of the jigsaw became apparent in the early stages of the HIV pandemic in the 80s and 90s.