Publications by authors named "Liam M Grover"

103 Publications

Thermosensitive collagen/fibrinogen gels loaded with decorin suppress lesion site cavitation and promote functional recovery after spinal cord injury.

Sci Rep 2021 Sep 13;11(1):18124. Epub 2021 Sep 13.

Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.

The treatment of spinal cord injury (SCI) is a complex challenge in regenerative medicine, complicated by the low intrinsic capacity of CNS neurons to regenerate their axons and the heterogeneity in size, shape and extent of human injuries. For example, some contusion injuries do not compromise the dura mater and in such cases implantation of preformed scaffolds or drug delivery systems may cause further damage. Injectable in situ thermosensitive scaffolds are therefore a less invasive alternative. In this study, we report the development of a novel, flowable, thermosensitive, injectable drug delivery system comprising bovine collagen (BC) and fibrinogen (FB) that forms a solid BC/FB gel (Gel) immediately upon exposure to physiological conditions and can be used to deliver reparative drugs, such as the naturally occurring anti-inflammatory, anti-scarring agent Decorin, into adult rat spinal cord lesion sites. In dorsal column lesions of adult rats treated with the Gel + Decorin, cavitation was completely suppressed and instead lesion sites became filled with injury-responsive cells and extracellular matrix materials, including collagen and laminin. Decorin increased the intrinsic potential of dorsal root ganglion neurons (DRGN) by increasing their expression of regeneration associated genes (RAGs), enhanced local axon regeneration/sprouting, as evidenced both histologically and by improved electrophysiological, locomotor and sensory function recovery. These results suggest that this drug formulated, injectable hydrogel has the potential to be further studied and translated into the clinic.
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http://dx.doi.org/10.1038/s41598-021-97604-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438067PMC
September 2021

Hybrid reflection retrieval method for terahertz dielectric imaging of human bone.

Biomed Opt Express 2021 Aug 12;12(8):4807-4820. Epub 2021 Jul 12.

School of Physics and Astronomy, University of Birmingham, Birmingham B15 2TT, UK.

Terahertz imaging is becoming a biological imaging modality in its own right, alongside the more mature infrared and X-ray techniques. Nevertheless, extraction of hyperspectral, biometric information of samples is limited by experimental challenges. Terahertz time domain spectroscopy reflection measurements demand highly precise alignment and suffer from limitations of the sample thickness. In this work, a novel hybrid Kramers-Kronig and Fabry-Pérot based algorithm has been developed to overcome these challenges. While its application is demonstrated through dielectric retrieval of glass-backed human bone slices for prospective characterisation of metastatic defects or osteoporosis, the generality of the algorithm offers itself to wider application towards biological materials.
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http://dx.doi.org/10.1364/BOE.427648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407848PMC
August 2021

Repeated exposure of nosocomial pathogens to silver does not select for silver resistance but does impact ciprofloxacin susceptibility.

Acta Biomater 2021 Jul 28. Epub 2021 Jul 28.

School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, United Kingdom. Electronic address:

The rise of antimicrobial resistant bacteria coupled with a void in antibiotic development marks Antimicrobial Resistance as one of the biggest current threats to modern medicine. Antimicrobial metals are being developed and used as alternative anti-infectives, however, the existence of known resistance mechanisms and limited data regarding bacterial responses to long-term metal exposure are barriers to widespread implementation. In this study, a panel of reference and clinical strains of major nosocomial pathogens were subjected to serial dosage cycles of silver and ciprofloxacin. Populations exposed to silver initially showed no change in sensitivity, however, increasingly susceptibility was observed after the 25th cycle. A control experiment with ciprofloxacin revealed a selection for resistance over time, with silver treated bacteria showing faster adaptation. Morphological analysis revealed filamentation in Gram negative species suggesting membrane perturbation, while sequencing of isolated strains identified mutations in numerous genes. These included those encoding for efflux systems, chemosensory systems, stress responses, biofilm formation and respiratory chain processes, although no consistent locus was identified that correlated with silver sensitivity. These results suggest that de novo silver resistance is hard to select in a range of nosocomial pathogens, although silver exposure may detrimentally impact sensitivity to antibiotics in the long term. STATEMENT OF SIGNIFICANCE: The adaptability of microbial life continuously calls for the development of novel antibiotic molecules, however, the cost and risk associated with their discovery have led to a drying up in the pipeline, causing antimicrobial resistance (AMR) to be a major threat to healthcare. From all available strategies, antimicrobial metals and, more specifically, silver showcase large bactericidal spectrum and limited toxic effect which coupled with a large range of processes available for their delivery made these materials as a clear candidate to tackle AMR. Previous reports have shown the ability of this metal to enact a synergistic effect with other antimicrobial therapies, nevertheless, the discovery of Ag resistance mechanisms since the early 70s and limited knowledge on the long term influence of silver on AMR poses a threat to their applicability. The present study provides quantitative data on the influence of silver based therapies on AMR development for a panel of reference and clinical strains of major nosocomial pathogens, revealing that prolonged silver exposure may detrimentally impact sensitivity to antibiotics.
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http://dx.doi.org/10.1016/j.actbio.2021.07.056DOI Listing
July 2021

Tailoring Therapeutic Responses via Engineering Microenvironments with a Novel Synthetic Fluid Gel.

Adv Healthc Mater 2021 08 23;10(16):e2100622. Epub 2021 Jun 23.

Healthcare Technologies Institute, University of Birmingham, Birmingham, B15 2TT, UK.

This study reports the first fully synthetic fluid gel (SyMGels) using a simple poly(ethylene glycol) polymer. Fluid gels are an interesting class of materials: structured during gelation via shear-confinement to form microparticulate suspensions, through a bottom-up approach. Structuring in this way, when compared to first forming a gel and subsequently breaking it down, results in the formation of a particulate dispersion with particles "grown" in the shear flow. Resultantly, systems form a complex microstructure, where gelled particles concentrate remaining non-gelled polymer within the continuous phase, creating an amorphous-like interstitial phase. As such, these materials demonstrate mechanical characteristics typical of colloidal glasses, presenting solid-like behaviors at rest with defined yielding; likely through intrinsic particle-particle and particle-polymer interactions. To date, fluid gels have been fabricated using polysaccharides with relatively complex chemistries, making further modifications challenging. SyMGels are easily functionalised, using simple click-chemistry. This chemical flexibility, allows the creation of microenvironments with discrete biological decoration. Cellular control is demonstrated using MSC (mesenchymal stem cells)/chondrocytes and enables the regulation of key biomarkers such as aggrecan and SOX9. These potential therapeutic platforms demonstrate an important advancement in the biomaterial field, underpinning the mechanisms which drive their mechanical properties, and providing a versatile delivery system for advanced therapeutics.
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http://dx.doi.org/10.1002/adhm.202100622DOI Listing
August 2021

Formulation of inherently antimicrobial magnesium oxychloride cement and the effect of supplementation with silver phosphate.

Mater Sci Eng C Mater Biol Appl 2021 Jul 30;126:112158. Epub 2021 Apr 30.

School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT, United Kingdom. Electronic address:

The growing threat of bacterial resistance to antibiotics is driving an increasing need for new antimicrobial strategies. This work demonstrates the potential of magnesium oxychloride cements (MOC) to be used as inorganic antimicrobial biomaterials for bone augmentation. An injectable formulation was identified at a powder to liquid ratio of 1.4 g mL, with an initial setting time below 30 mins and compressive strength of 35 ± 9 MPa. Supplementation with AgPO to enhance the antimicrobial efficacy of MOC was explored, and shown via real time X-ray diffraction to retard the formation of hydrated oxychloride phases by up to 30%. The antimicrobial efficacy of MOC was demonstrated in vitro against Staphylococcus aureus and Pseudomonas aeruginosa, forming zones of inhibition and significantly reducing viability in broth culture. Enhanced efficacy was seen for silver doped formulations, with complete eradication of detectable viable colonies within 3 h, whilst retaining the cytocompatibility of MOC. Investigating the antimicrobial mode of action revealed that Mg and Ag release and elevated pH contributed to MOC efficacy. Sustained silver release was demonstrated over 14 days, suggesting the AgPO modified formulation offers two mechanisms of infection treatment, combining the inherent antimicrobial properties of MOC with controlled release of inorganic antimicrobials.
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http://dx.doi.org/10.1016/j.msec.2021.112158DOI Listing
July 2021

Formulation of a Composite Nasal Spray Enabling Enhanced Surface Coverage and Prophylaxis of SARS-COV-2.

Adv Mater 2021 Jul 31;33(26):e2008304. Epub 2021 May 31.

Healthcare Technology Institute, School of Chemical Engineering, University of Birmingham, Birmingham, B15 2TT, UK.

Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, particularly the nasal region. However, there is little in the way of adequate intervention that can protect an individual or prevent further spread. This study reports on a nasal formulation with the capacity to combat such challenges, focusing on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Formulation of a polysaccharide-based spray, known for its mucoadhesive properties, is undertaken and it is characterized for its mechanical, spray distribution, and antiviral properties. The ability to engineer key mechanical characteristics such as dynamic yield stresses and high coverage is shown, through systematic understanding of the composite mixture containing both gellan and λ-carrageenan. Furthermore, the spray systems demonstrate highly potent capacities to prevent SARS-CoV-2 infection in Vero cells, resulting in complete inhibition when either treating, the cells, or the virus, prior to challenging for infection. From this data, a mechanism for both prophylaxis and prevention is proposed; where entrapment within a polymeric coating sterically blocks virus uptake into the cells, inactivating the virus, and allowing clearance within the viscous medium. As such, a fully preventative spray is formulated, targeted at protecting the lining of the upper respiratory pathways against SARS-CoV-2.
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http://dx.doi.org/10.1002/adma.202008304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212080PMC
July 2021

Trabecular bone organoids: a micron-scale 'humanised' prototype designed to study the effects of microgravity and degeneration.

NPJ Microgravity 2021 May 21;7(1):17. Epub 2021 May 21.

School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, UK.

Bone is a highly responsive organ, which continuously adapts to the environment it is subjected to in order to withstand metabolic demands. These events are difficult to study in this particular tissue in vivo, due to its rigid, mineralised structure and inaccessibility of the cellular component located within. This manuscript presents the development of a micron-scale bone organoid prototype, a concept that can allow the study of bone processes at the cell-tissue interface. The model is constructed with a combination of primary female osteoblastic and osteoclastic cells, seeded onto femoral head micro-trabeculae, where they recapitulate relevant phenotypes and functions. Subsequently, constructs are inserted into a simulated microgravity bioreactor (NASA-Synthecon) to model a pathological state of reduced mechanical stimulation. In these constructs, we detected osteoclastic bone resorption sites, which were different in morphology in the simulated microgravity group compared to static controls. Once encapsulated in human fibrin and exposed to analogue microgravity for 5 days, masses of bone can be observed being lost from the initial structure, allowing to simulate the bone loss process further. Constructs can function as multicellular, organotypic units. Large osteocytic projections and tubular structures develop from the initial construct into the matrix at the millimetre scale. Micron-level fragments from the initial bone structure are detected travelling along these tubules and carried to sites distant from the native structure, where new matrix formation is initiated. We believe this model allows the study of fine-level physiological processes, which can shed light into pathological bone loss and imbalances in bone remodelling.
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http://dx.doi.org/10.1038/s41526-021-00146-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140135PMC
May 2021

Formulation of a reactive oxygen producing calcium sulphate cement as an anti-bacterial hard tissue scaffold.

Sci Rep 2021 Feb 24;11(1):4491. Epub 2021 Feb 24.

School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, Northern Ireland, UK.

Prophylactic antibiotic bone cements are extensively used in orthopaedics. However, the development of antimicrobial resistance to antibiotics, demonstrates a need to find alternative treatments. Herein, an antimicrobial honey (SurgihoneyRO-SHRO) has been successfully incorporated into a calcium sulphate (CS) based cement to produce a hard tissue scaffold with the ability to inhibit bacterial growth. Antimicrobial properties elicited from SHRO are predominantly owed to the water-initiated production of reactive oxygen species (ROS). As an alternative to initially loading CS cement with SHRO, in order to prevent premature activation, SHRO was added into the already developing cement matrix, locking available water into the CS crystal structure before SHRO addition. Promisingly, this methodology produced > 2.5 times (715.0 ± 147.3 μM/mL/g) more ROS over 24 h and exhibited a compressive strength (32.2 ± 5.8 MPa) comparable to trabecular bone after 3 weeks of immersion. In-vitro the SHRO loaded CS scaffolds were shown to inhibit growth of clinically relevant organisms, Staphylococcus aureus and Pseudomonas aeruginosa, with comparable potency to equivalent doses of gentamicin. Encouragingly, formulations did not inhibit wound healing or induce an inflammatory response from osteoblasts. Overall this study highlights the prophylactic potential of CS-SHRO cements as an alternative to traditional antibiotics.
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http://dx.doi.org/10.1038/s41598-021-84060-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904759PMC
February 2021

Formulation of an antimicrobial superabsorbent powder that gels in situ to produce reactive oxygen.

Mater Sci Eng C Mater Biol Appl 2021 Jan 3;118:111479. Epub 2020 Sep 3.

School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom of Great Britain and Northern Ireland.

The enzymatic oxidation of glucose to produce reactive oxygen species (ROS) provides honey with antimicrobial efficacy. This mechanism offers an alternative to traditional antibiotics; however, topical use of honey is limited due to its adherent and highly viscous properties. This study aims to overcome these issues by engineering a powder-based system that eases delivery and offers in situ activation of ROS. Starch based drying agents were utilised to enable freeze drying of a medical honey, with methylated-β-cyclodextrin (MCD) enabling the highest active incorporation (70%) while still producing a free-flowing powder. Addition of a superabsorbent, sodium polyacrylate (≤40%) was shown to facilitate in situ gelation of the powder, with an absorption capacity of up to 120.7 ± 4.5 mL g. Promisingly efficacy of the optimised superabsorbent powder was demonstrated in vitro against several clinically relevant Gram-negative and Gram-positive bacteria (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa). Alongside this no adverse effects were observed against human dermal fibroblasts. Application of the superabsorbent powder in an ex-vivo porcine wound model revealed capability to form a protective hydrogel barrier in less than 1 min. Overall, this novel ROS producing superabsorbent powder has potential to tackle topical infections without using traditional antibiotics.
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http://dx.doi.org/10.1016/j.msec.2020.111479DOI Listing
January 2021

Selective Laser Melting of Ti-6Al-4V: The Impact of Post-processing on the Tensile, Fatigue and Biological Properties for Medical Implant Applications.

Materials (Basel) 2020 Jun 22;13(12). Epub 2020 Jun 22.

School of Materials and Metallurgy, University of Birmingham, Edgbaston B15 2TT, UK.

One of the main challenges in additive manufacturing (AM) of medical implants for the treatment of bone tissue defects is to optimise the mechanical and biological performance. The use of post-processing can be a necessity to improve the physical properties of customised AM processed implants. In this study, Ti-6Al-4V coupons were manufactured using selective laser melting (SLM) in two build orientations (vertical and horizontal) and subsequently post-processed using combinations of hot isostatic pressing (HIP), sandblasting (SB), polishing (PL) and chemical etching (CE). The effect of the different post-manufacturing strategies on the tensile and fatigue performance of the SLMed parts was investigated and rationalised by observing the surface topography. Vertically built samples showed higher yield strength (YS) and ultimate tensile strength (UTS) than the horizontal samples, increasing from 760.9 ± 22.3 MPa and 961.3 ± 50.2 MPa in the horizontal condition to 820.09 ± 16.5 MPa and 1006.7 ± 6.3 MPa in the vertical condition, respectively. After the HIP treatment, the ductility was substantially improved in both orientations; by 2.1 and 2.9 folds in the vertical and horizontal orientations, respectively. The vertically built samples demonstrated a superior ductility of 22% following HIP and polishing. Furthermore, chemical etching was found to be the most effective surface post-processing treatment to improve the fatigue performance after HIP, achieving the highest run-out strength of 450 MPa. Most importantly, chemical etching after HIP enhanced the cellular affinity of the surface, in addition to its good fatigue performance, making it a promising post-processing approach for bone implants where tissue integration is needed.
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http://dx.doi.org/10.3390/ma13122813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345457PMC
June 2020

The Quantification of Injectability by Mechanical Testing.

J Vis Exp 2020 05 13(159). Epub 2020 May 13.

School of Chemical Engineering, University of Birmingham.

Injectable biomaterials are becoming increasingly popular for the minimally invasive delivery of drugs and cells. These materials are typically more viscous than traditional aqueous injections and may be semi-solid, therefore, their injectability cannot be assumed. This protocol describes a method to objectively assess the injectability of these materials using a standard mechanical tester. The syringe plunger is compressed by the crosshead at a set rate, and the force is measured. The maximum or plateau force value can then be used for comparison between samples, or to an absolute force limit. This protocol can be used with any material, and any syringe and needle size or geometry. The results obtained may be used to make decisions about formulations, syringe and needle sizes early in the translational process. Further, the effects of altering formulations on injectability may be quantified, and the optimum time to inject temporally changing materials determined. This method is also suitable as a reproducible way to examine the effects of injection on a material, to study phenomena such as self-healing and filter pressing or study the effects of injection on cells. This protocol is faster and more directly applicable to injectability than rotational rheology, and requires minimal post processing to obtain key values for direct comparisons.
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http://dx.doi.org/10.3791/61417DOI Listing
May 2020

Hexametaphosphate as a potential therapy for the dissolution and prevention of kidney stones.

J Mater Chem B 2020 06;8(24):5215-5224

School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.

The incidence of kidney stones is increasing worldwide, and recurrence is common (50% within 5 years). Citrate, the current gold standard therapy, which is usually given as potassium or sodium salts, is used because it raises urine pH and chelates calcium, the primary component of up to 94% of stones. In this study hexametaphosphate (HMP), a potent calcium chelator, was found to be 12 times more effective at dissolving calcium oxalate, the primary component of kidney stones, than citrate. HMP was also observed to be effective against other common kidney stone components, namely calcium phosphate and struvite (magnesium ammonium phosphate). Interestingly, HMP was capable of raising the zeta potential of calcium oxalate particles from -15.4 to -34.6 mV, which may prevent stone growth by aggregation, the most rapid growth mechanism, and thus avert occlusion. Notably, HMP was shown to be up to 16 times as effective as citrate at dissolving human kidney stones under simulated physiological conditions. It may thus be concluded that HMP is a promising potential therapy for calcium and struvite kidney stones.
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http://dx.doi.org/10.1039/d0tb00343cDOI Listing
June 2020

The neuroregenerative effects of topical decorin on the injured mouse cornea.

J Neuroinflammation 2020 May 4;17(1):142. Epub 2020 May 4.

Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, 3053, Australia.

Background: The cornea is innervated with a rich supply of sensory nerves that play important roles in ocular surface health. Any injury or pathology of the corneal nerves increases the risk of dry eye disease and infection. This study aims to evaluate the therapeutic potential of topical decorin to improve corneal nerve regeneration in a mouse model of sterile epithelial abrasion injury.

Methods: Bilateral central corneal epithelial abrasions (2-mm, Alger Brush) were performed on young C57BL/6 J mice to remove the corneal sensory nerves. Decorin, or vehicle, was applied topically, three times per day for 1 week or every 2 h for 6 h. Spectral-domain optical coherence tomography was performed to measure the abrasion area and corneal thickness. Wholemount immunofluorescence staining was used to assess sensory nerve regeneration (β-tubulin III) and immune cell density (CD45, Iba1, CD11c). To investigate the specific role of dendritic cells (DCs), Cx3cr1 mice, which spontaneously lack resident corneal epithelial DCs, were also investigated. The effect of prophylactic topical administration of recombinant human decorin (applied prior to the abrasion) was also investigated. Nerve tracing (NeuronJ software) was performed to compare recovery of basal nerve axons and superficial nerve terminals in the central and peripheral cornea.

Results: At 6 h after injury, topical decorin application was associated with greater intraepithelial DC recruitment but no change in re-epithelialisation or corneal thickness, compared to the vehicle control. One week after injury, sub-basal nerve plexus and superficial nerve terminal density were significantly higher in the central cornea in the decorin-treated eyes. The density of corneal stromal macrophages in the decorin-treated eyes and their contralateral eyes was significantly lower compared to saline-treated corneas. No significant improvement in corneal nerve regeneration was observed in Cx3cr1 mice treated with decorin.

Conclusions: Decorin promotes corneal epithelial nerve regeneration after injury. The neuroregenerative effect of topical decorin was associated with a higher corneal DC density during the acute phase, and fewer macrophages at the study endpoint. The corneal neuroregenerative effects of decorin were absent in mice lacking intraepithelial DCs. Together, these findings support a role for decorin in DC-mediated neuroregeneration following corneal abrasion injury.
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http://dx.doi.org/10.1186/s12974-020-01812-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199348PMC
May 2020

Filling the Gap: A Correlation between Objective and Subjective Measures of Injectability.

Adv Healthc Mater 2020 03 24;9(5):e1901521. Epub 2020 Jan 24.

School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, UK.

Various injectable biomaterials are developed for the minimally invasive delivery of therapeutics. Typically, a mechanical tester is used to ascertain the force required to inject these biomaterials through a given syringe-needle system. However, currently there is no method to correlate the force measured in the laboratory to the perceived effort required to perform that injection by the end user. In this article, the injection force (F) for a variety of biomaterials, displaying a range of rheological properties, is compared with the effort scores from a 50 person panel study. The maximum injection force measured at crosshead speed 1 mm s is a good proxy for injection effort, with an R of 0.89. This correlation leads to the following conclusions: participants can easily inject 5 mL of substance for F < 12 N; considerable effort is required to inject 5 mL for 12 N < F < 38 N; great effort is required and <5 mL can be injected for 38 N < F < 64 N; and materials are entirely non-injectable for F > 64 N. These values may be used by developers of injectable biomaterials to make decisions about formulations and needle sizes early in the translational process.
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http://dx.doi.org/10.1002/adhm.201901521DOI Listing
March 2020

Corrigendum: Osteoblast-Derived Vesicle Protein Content Is Temporally Regulated During Osteogenesis: Implications for Regenerative Therapies.

Front Bioeng Biotechnol 2019;7:392. Epub 2019 Dec 6.

School of Chemical Engineering, University of Birmingham, Birmingham, United Kingdom.

[This corrects the article DOI: 10.3389/fbioe.2019.00092.].
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http://dx.doi.org/10.3389/fbioe.2019.00392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910068PMC
December 2019

Chemobrionic structures in tissue engineering: self-assembling calcium phosphate tubes as cellular scaffolds.

Biomater Sci 2020 Feb 12;8(3):812-822. Epub 2019 Dec 12.

School of Chemical Engineering, University of Birmingham, B15 2TT, UK.

A diverse range of complex patterns and mineralised hierarchical microstructures can be derived from chemobrionic systems, with formation driven by complex reaction-diffusion mechanisms far from thermodynamic equilibrium. In these experiments, self-assembling calcium phosphate tubes are generated using hydrogels made with 1 M calcium solutions layered with solutions of dibasic sodium phosphate over a range of concentrations between 0.2-1 M. Self-assembling structures prepared using 0.8 M dibasic sodium phosphate solutions were selected to assess cell-material interactions. Candidate chemobrionic scaffolds were characterised by micro-X-Ray fluorescence (μ-XRF) spectroscopy, Raman spectroscopy, powder X-ray diffraction (XRD), helium pycnometry and scanning electron microscopy (SEM). As prepared tubes were formed from non-stoichiometric hydroxyapatite (HA, Ca(PO)(HPO)(OH) (0 ≤x≤ 1)), which was confirmed as calcium deficient hydroxyapatite (CDHA, Ca(PO)HPOOH). Thermal treatment of tubes in air at 650 °C for 4 h converted the structures to beta tricalcium phosphate (β-TCP, β-Ca(PO)). The potential of these scaffolds to support the attachment of bone marrow derived mesenchymal stem cells (BMSCs) was investigated for the first time, and we demonstrate cell attachment and elongation on the fabricated tubular structures.
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http://dx.doi.org/10.1039/c9bm01010fDOI Listing
February 2020

Critical and diverse roles of phosphates in human bone formation.

J Mater Chem B 2019 12 15;7(47):7460-7470. Epub 2019 Nov 15.

School of Chemical Engineering, University of Birmingham, B15 2TT, UK.

Humans utilise biomineralisation in the formation of bone and teeth. Human biomineralisation processes are defined by the transformation of an amorphous phosphate-based precursor to highly organised nanocrystals. Interestingly, ionic phosphate species not only provide a fundamental building block of biological mineral, but rather exhibit several diverse roles in mediating mineral formation in the physiological milieu. In this review, we focus on elucidating the complex roles of phosphate ions and molecules within human biomineralisation pathways, primarily referring to the nucleation and crystallisation of bone mineral.
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http://dx.doi.org/10.1039/c9tb02011jDOI Listing
December 2019

Rubidium-containing mesoporous bioactive glass scaffolds support angiogenesis, osteogenesis and antibacterial activity.

Mater Sci Eng C Mater Biol Appl 2019 Dec 1;105:110155. Epub 2019 Sep 1.

Department of Materials Engineering, Monash University, Victoria 3800, Australia.

In this study, rubidium-containing mesoporous bioglass (Rb-MBG) scaffolds were formed with the investigation of the influence of Rb addition on angiogenic and osteogenic differentiation abilities of hBMSC. The phase composition, microstructure, pore size distribution, ion release, biological activity, drug loading rate, and release rate of Rb-MBG were characterized. The proliferation and differentiation of hBMSC, the markers of bone formation (ALP, COL-1) and angiogenesis (VEGF, HIF-1α), and wnt/β-catenin related-signaling pathway gene were studied by cell culture. Rb-MBG loaded with antibacterial agents enoxacin (ENX), coliforms and Staphylococcus aureus were cultured together to study the antibacterial effects. The results indicate that the samples have a 350-550 μm large pore structure and 4.5-5.5 nm mesoporous size. Adding Rb can increase the activity of ALP, the secretion of VEGF and COLI, and the expression of HIF-1α of hBMSCs. Rb containing MBG is likely to enhance the proliferation and differentiation of hBMSCs through the influence of Wnt/ß-catenin signal path. Rb-MBG scaffold can load effectively and release Rb ions and ENX continuously to damage the bacterial cell membrane with the synergistic effect, and therefore achieve antibacterial results. In conclusion, adding Rb to MBG supports angiogenesis and osteogenesis of hBMSCs, as well as antibacterial activity.
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http://dx.doi.org/10.1016/j.msec.2019.110155DOI Listing
December 2019

Antimicrobial emulsions: Formulation of a triggered release reactive oxygen delivery system.

Mater Sci Eng C Mater Biol Appl 2019 Oct 9;103:109735. Epub 2019 May 9.

School of Chemical Engineering, University of Birmingham, Edgbaston, B15 2TT, United Kingdom of Great Britain and Northern Ireland. Electronic address:

The enzyme glucose oxidase mediates the oxidation of glucose to produce reactive oxygen species (ROS), such as hydrogen peroxide. This reaction and its products are key to providing honey with its antimicrobial properties. Currently, honey is an adherent, highly viscous product that produces ROS by means of a water-initiated reaction. These properties reduce clinical usability and present a formulation problem for long term stability. This study aims to engineer a water-in-oil emulsion containing an engineered honey (SurgihoneyRO™) that is easy to administer topically and is controllably activated in-situ. Paraffin oil continuous emulsions formulated using the emulsifier polyglycerol polyricinoleate displayed shear-thinning characteristics. Viscosities between 1.4 and 19.3 Pa·s were achieved at a shear rate representative of post-mixing conditions (4.1 s) by changing the volume of the dispersed phase (30-60%). Notably, this wide viscosity range will be useful in tailoring future formulations for specific application mechanisms. When exposed to water and shear, these emulsion systems were found to undergo catastrophic phase inversion, evidenced by a change in conductivity from 0 μS in the non-aqueous state, to >180 μS in the sheared, inverted state. Encouragingly, sheared formulations containing ≥50% SurgihoneyRO™ generated sufficient levels of ROS to inhibit growth of clinically relevant Gram-positive and Gram-negative bacteria. This study demonstrates an ability to formulate ROS producing emulsions for use as an alternative to current topical antibiotic-based treatments. Promisingly, the ability of this system to release water-sensitive actives in response to shear may be useful for controlled delivery of other therapeutic molecules.
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http://dx.doi.org/10.1016/j.msec.2019.05.020DOI Listing
October 2019

Evidence of Intrinsic Impairment of Osteoblast Phenotype at the Curve Apex in Girls With Adolescent Idiopathic Scoliosis.

Spine Deform 2019 07;7(4):533-542

Institute of Inflammation and Ageing, MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity, University of Birmingham, Birmingham, United Kingdom. Electronic address:

Study Design: An observational descriptive study based on a single cohort of patients.

Objective: To determine whether spinal facet osteoblasts at the curve apex display a different phenotype to osteoblasts from outside the curve in adolescent idiopathic scoliosis (AIS) patients.

Summary Of Background Data: Intrinsic differences in the phenotype of spinal facet bone tissue and in spinal osteoblasts have been implicated in the pathology of AIS. However, no study has compared the phenotype of facet osteoblasts at the curve apex compared with outside the curve in AIS patients.

Methods: Facet spinal tissue was collected perioperatively from three sites, the concave and convex side at the curve apex and from outside the curve (noncurve) from three AIS female patients aged 13-16 years. Spinal tissue was analyzed by micro-computed tomography to determine bone mineral density (BMD) and trabecular structure. Primary osteoblasts were cultured from concave, convex, and noncurve facet bone chips. The phenotype of osteoblasts was determined by assessment of cellular proliferation, cellular metabolism (alkaline phosphatase and Seahorse Analyzer), bone nodule mineralization (Alizarin red assay), and the mRNA expression of Wnt signaling genes (quantitative reverse transcriptase polymerase chain reaction).

Results: Convex facet tissue exhibited greater BMD and trabecular thickness, compared with concave facet tissue. Osteoblasts at the convex side of the curve apex exhibited a significantly higher proliferative and metabolic phenotype and a greater capacity to form mineralized bone nodules, compared with concave osteoblasts. mRNA expression of SKP2 was significantly greater in both concave and convex osteoblasts, compared with noncurve osteoblasts. The expression of SFRP1 was significantly downregulated in convex osteoblasts, compared with either concave or noncurve.

Conclusions: Intrinsic differences that affect osteoblast function are exhibited by spinal facet osteoblasts at the curve apex in AIS patients.

Level Of Evidence: Level IV, Prognostic.
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http://dx.doi.org/10.1016/j.jspd.2018.11.016DOI Listing
July 2019

Improving our understanding of metal implant failures: Multiscale chemical imaging of exogenous metals in ex-vivo biological tissues.

Acta Biomater 2019 10 5;98:284-293. Epub 2019 Jun 5.

University of Birmingham, Birmingham B15 2TT, UK; University of Alberta, Edmonton, AB T6G, Canada. Electronic address:

Biological exposures to micro- and nano-scale exogenous metal particles generated as a consequence of in-service degradation of orthopaedic prosthetics can result in severe adverse tissues reactions. However, individual reactions are highly variable and are not easily predicted, due to in part a lack of understanding of the speciation of the metal-stimuli which dictates cellular interactions and toxicity. Investigating the chemistry of implant derived metallic particles in biological tissue samples is complicated by small feature sizes, low concentrations and often a heterogeneous speciation and distribution. These challenges were addressed by developing a multi-scale two-dimensional X-ray absorption spectroscopic (XAS) mapping approach to discriminate sub-micron changes in particulate chemistry within ex-vivo tissues associated with failed CoCrMo total hip replacements (THRs). As a result, in the context of THRs, we demonstrate much greater variation in Cr chemistry within tissues compared with previous reports. Cr compounds including phosphate, hydroxide, oxide, metal and organic complexes were observed and correlated with Co and Mo distributions. This variability may help explain the lack of agreement between biological responses observed in experimental exposure models and clinical outcomes. The multi-scale 2D XAS mapping approach presents an essential tool in discriminating the chemistry in dilute biological systems where speciation heterogeneity is expected. SIGNIFICANCE: Metal implants are routinely used in healthcare but may fail following degradation in the body. Although specific implants can be identified as 'high-risk', our analysis of failures is limited by a lack of understanding of the chemistry of implant metals within the peri-prosthetic milieu. A new approach to identify the speciation and variability in speciation at sub-micron resolution, of dilute exogenous metals within biological tissues is reported; applied to understanding the failure of metallic (CoCrMo) total-hip-replacements widely used in orthopedic surgery. Much greater variation in Cr chemistry was observed compared with previous reports and included phosphate, hydroxide, oxide, metal and organic complexes. This variability may explain lack of agreement between biological responses observed in experimental exposure models and clinical outcomes.
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http://dx.doi.org/10.1016/j.actbio.2019.05.071DOI Listing
October 2019

Osteoblast-Derived Vesicle Protein Content Is Temporally Regulated During Osteogenesis: Implications for Regenerative Therapies.

Front Bioeng Biotechnol 2019 1;7:92. Epub 2019 May 1.

School of Chemical Engineering, University of Birmingham, Birmingham, United Kingdom.

Osteoblast-derived extracellular vesicles (EV) are a collection of secreted (sEVs) and matrix-bound nanoparticles that function as foci for mineral nucleation and accumulation. Due to the fact sEVs can be isolated directly from the culture medium of mineralizing osteoblasts, there is growing interest their application regenerative medicine. However, at present therapeutic advancements are hindered by a lack of understanding of their precise temporal contribution to matrix mineralization. This study advances current knowledge by temporally aligning sEV profile and protein content with mineralization status. sEVs were isolated from mineralizing primary osteoblasts over a period of 1, 2, and 3 weeks. Bimodal particle distributions were observed (weeks 1 and 3: 44 and 164 nm; week 2: 59 and 220 nm), indicating a heterogeneous population with dimensions characteristic of exosome- (44 and 59 nm) and microvesicle-like (164 and 220 nm) particles. Proteomic characterization by liquid chromatography tandem-mass spectrometry (LC-MS/MS) revealed a declining correlation in EV-localized proteins as mineralization advanced, with Pearson correlation-coefficients of 0.79 (week 1 vs. 2), 0.6 (2 vs. 3) and 0.46 (1 vs. 3), respectively. Principal component analysis (PCA) further highlighted a time-dependent divergence in protein content as mineralization advanced. The most significant variations were observed at week 3, with a significant ( < 0.05) decline in particle concentration, visual evidence of EV rupture and enhanced mineralization. A total of 116 vesicle-localized proteins were significantly upregulated at week 3 (56% non-specifically, 19% relative to week 1, 25% relative to week 2). Gene ontology enrichment analysis of these proteins highlighted overrepresentation of genes associated with matrix organization. Of note, increased presence of phospholipid-binding and calcium channeling annexin proteins (A2, A5, and A6) indicative of progressive variations in the nucleational capacity of vesicles, as well as interaction with the surrounding ECM. We demonstrate sEV-mediated mineralization is dynamic process with variations in vesicle morphology and protein content having a potential influence on developmental changes matrix organization. These findings have implications for the selection and application of EVs for regenerative applications.
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http://dx.doi.org/10.3389/fbioe.2019.00092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504811PMC
May 2019

A self-healing hydrogel eye drop for the sustained delivery of decorin to prevent corneal scarring.

Biomaterials 2019 07 20;210:41-50. Epub 2019 Apr 20.

School of Chemical Engineering, University of Birmingham, Birmingham, BI5 2TT, UK. Electronic address:

Scarring/Opacity on the surface of the eye and vascularisation following infectious diseases, inflammation and corneal trauma are often a leading cause of blindness. The 'gold standard' treatment to prevent corneal scarring is the application of amniotic membrane (AM) to the ocular surface in the acute stage of injury. Although clinically effective, the use of the AM is associated with biological variability and unpredictable responses. Potential health risks including disease transmission, significant ethical issues surrounding the tissue donation process and stringent regulations/storage conditions, preclude widespread use. Consequently, there is a demand for the development of a new, synthetic alternative, that is stable at room temperature, capable of protecting the wound and has the capacity to deliver anti-scarring and anti-inflammatory mediators. Here we have developed a micro-structured fluid gel eye drop, to deliver a potent anti-scarring molecule, decorin. We have compared the release of decorin from the formulated dressing to a typical gel film, demonstrating enhanced release for the fluid gel eye-drops. Therefore, we have investigated the effect of the fluid gel system in 2D human corneal fibroblast culture models, as well as shown the retention of the gellan fluid gel in an in vivo rat model. At the same time the efficacy of the fluid gel eye drop was studied in an organ culture model, whereby the fluid gel containing decorin, significantly (P < 0.05) increased re-epithelialisation within 4 days of treatment.
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http://dx.doi.org/10.1016/j.biomaterials.2019.04.013DOI Listing
July 2019

Physical Structuring of Injectable Polymeric Systems to Controllably Deliver Nanosized Extracellular Vesicles.

Adv Healthc Mater 2019 05 6;8(9):e1801604. Epub 2019 Mar 6.

School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.

Extracellular vesicles (EVs) are emerging as a promising alternative approach to cell-therapies. However, to realize the potential of these nanoparticles as new regenerative tools, healthcare materials that address the current limitations of systemic administration need to be developed. Here, two technologies for controlling the structure of alginate based microgel suspensions are used to develop sustained local release of EVs, in vitro. Microparticles formed using a shearing technique are compared to those manufactured using vibrational technology, resulting in either anisotropic sheet-like or spheroid particles, respectively. EVs harvested from preosteoblasts are isolated using differential ultracentrifugation and successfully loaded into the two systems, while maintaining their structures. Promisingly, in addition to exhibiting even EV distribution and high stability, controlled release of vesicles from both structures is exhibited, in vitro, over the 12 days studied. Interestingly, a significantly greater number of EVs are released from the suspensions formed by shearing (69.9 ± 10.5%), compared to the spheroids (35.1 ± 7.6%). Ultimately, alterations to the hydrogel physical structures have shown to tailor nanoparticle release while simultaneously providing ideal material characteristics for clinical injection. Thus, the sustained release mechanisms achieved through manipulating the formation of such biomaterials provide a key to unlocking the therapeutic potential held within EVs.
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http://dx.doi.org/10.1002/adhm.201801604DOI Listing
May 2019

Organotypic Culture of Bone-Like Structures Using Composite Ceramic-Fibrin Scaffolds.

Curr Protoc Stem Cell Biol 2019 02 14;48(1):e79. Epub 2019 Jan 14.

School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, United Kingdom.

We have developed an organotypic culture system that allows the production of bone tissue features on a centimeter scale. A composite, calcium phosphate-strained fibrin gel system is able to organize itself in the presence of osteoblastic cells, creating basic hierarchical units as seen in vivo, and can be modified to produce a range of other tissues that require such directional structuring. Constructs evolve over time into multi-compositional structures containing a high mineral content and terminally differentiated, osteocyte-like cells. These tissues can be cultured over extended durations (exceeding 1 year) and are responsive to a variety of chemical and biological agents. The platform can reduce the number of animals used in experimentation by acting as an intermediate stage in which more personalized research conditions can be generated. We provide a thorough description of the protocol used to successfully culture and modify this system, as well as guidance on compositional characterization. © 2019 by John Wiley & Sons, Inc.
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http://dx.doi.org/10.1002/cpsc.79DOI Listing
February 2019

Sustained release of decorin to the surface of the eye enables scarless corneal regeneration.

NPJ Regen Med 2018 21;3:23. Epub 2018 Dec 21.

2School of Chemical Engineering, University of Birmingham, Birmingham, B15 2TT UK.

Disorganization of the transparent collagenous matrix in the cornea, as a consequence of a variety of infections and inflammatory conditions, leads to corneal opacity and sight-loss. Such corneal opacities are a leading cause of blindness, according to the WHO. Public health programs target prevention of corneal scarring, but the only curative treatment of established scarring is through transplantation. Although attempts to minimize corneal scarring through aggressive control of infection and inflammation are made, there has been little progress in the development of anti-scarring therapies. This is owing to eye drop formulations using low viscosity or weak gelling materials having short retention times on the ocular surface. In this study, we report an innovative eye drop formulation that has the ability to provide sustained delivery of decorin, an anti-scarring agent. The novelty of this eye drop lies in the method of structuring during manufacture, which creates a material that can transition between solid and liquid states, allowing retention in a dynamic environment being slowly removed through blinking. In a murine model of , applying the eye drop resulted in reductions of corneal opacity within 16 days. More remarkably, the addition of hrDecorin resulted in restoration of corneal epithelial integrity with minimal stromal opacity endorsed by reduced α-smooth muscle actin (αSMA), fibronectin, and laminin levels. We believe that this drug delivery system is an ideal non-invasive anti-fibrotic treatment for patients with microbial keratitis, potentially without recourse to surgery, saving the sight of many in the developing world, where corneal transplantation may not be available.
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http://dx.doi.org/10.1038/s41536-018-0061-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303295PMC
December 2018

Formulation of a covalently bonded hydroxyapatite and poly(ether ether ketone) composite.

J Tissue Eng 2018 Jan-Dec;9:2041731418815570. Epub 2018 Dec 17.

School of Chemical Engineering, University of Birmingham, Birmingham, UK.

Spinal fusion devices can be fabricated from composites based on combining hydroxyapatite and poly(ether ether ketone) phases. These implants serve as load-bearing scaffolds for the formation of new bone tissue between adjacent vertebrae. In this work, we report a novel approach to covalently bond hydroxyapatite and poly(ether ether ketone) to produce a novel composite formulation with enhanced interfacial adhesion between phases. Compared to non-linked composites (HA_PEEK), covalently linked composites (HA_L_PEEK), loaded with 1.25 vol% hydroxyapatite, possessed a greater mean flexural strength (170 ± 5.4 vs 171.7 ± 14.8 MPa (mean ± SD)) and modulus (4.8 ± 0.2 vs 5.0 ± 0.3 GPa (mean ± SD)). Although the mechanical properties were not found to be significantly different (p > 0.05), PEEK_L_HA contained substantially larger hydroxyapatite inclusions (100-1000 µm) compared to HA_PEEK (50-200 µm), due to the inherently agglomerative nature of the covalently bonded hydroxyapatite and poly(ether ether ketone) additive. Larger inclusions would expectedly weaken the HA_L_PEEK composite; however, there is no significant difference between the flexural modulus of poly(ether ether ketone) with respect to HA_L_PEEK (p = 0.13). In addition, the flexural modulus of HA_PEEK is significantly lower compared to poly(ether ether ketone) (p = 0.03). Ultimately, covalent linking reduces hydroxyapatite particulate de-bonding from the polymeric matrix and inhibits micro-crack development, culminating in enhanced transfer of stiffness between hydroxyapatite and poly(ether ether ketone) under loading.
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http://dx.doi.org/10.1177/2041731418815570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299303PMC
December 2018

The design of additively manufactured lattices to increase the functionality of medical implants.

Mater Sci Eng C Mater Biol Appl 2019 Jan 13;94:901-908. Epub 2018 Oct 13.

School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.

The rise of antibiotic resistant bacterial species is driving the requirement for medical devices that minimise infection risks. Antimicrobial functionality may be achieved by modifying the implant design to incorporate a reservoir that locally releases a therapeutic. For this approach to be successful it is critical that mechanical functionality of the implant is maintained. This study explores the opportunity to exploit the design flexibilities possible using additive manufacturing to develop porous lattices that maximise the volume available for drug loading while maintaining load-bearing capacity of a hip implant. Eight unit cell types were initially investigated and a volume fraction of 30% was identified as the lowest level at which all lattices met the design criteria in ISO 13314. Finite element analysis (FEA) identified three lattice types that exhibited significantly lower displacement (10-fold) compared with other designs; Schwartz primitive, Schwartz primitive pinched and cylinder grid. These lattices were additively manufactured in Ti-6Al-4V using selective laser melting. Each design exceeded the minimum strength requirements for orthopaedic hip implants according to ISO 7206-4. The Schwartz primitive (Pinched) lattice geometry, with 10% volume fill and a cubic unit cell period of 10, allowed the greatest void volume of all lattice designs whilst meeting the fatigue requirements for use in an orthopaedic implant (ISO 7206-4). This paper demonstrates an example of how additive manufacture may be exploited to add additional functionality to medical implants.
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http://dx.doi.org/10.1016/j.msec.2018.10.052DOI Listing
January 2019

Influence of Cobalt Ions on Collagen Gel Formation and Their Interaction with Osteoblasts.

ACS Omega 2018 Aug 30;3(8):10129-10138. Epub 2018 Aug 30.

Physical Sciences for Health, School of Chemistry, Physical Sciences of Imaging in the Biomedical Sciences, School of Chemistry, Department of BioChemical Engineering, School of Chemical Engineering, and School of Dentistry, University of Birmingham, Edgbaston, B15 2TT Birmingham, U.K.

Metals on metal implants have long been used in arthroplasties because of their robustness and low dislocation rate. Several relatively low-corrosion metals have been used in arthroplasty, including 316L stainless steel, titanium, and cobalt-chromium-molybdenum alloy. Debris from these implants, however, has been found to cause inflammatory responses leading to unexpected failure rates approaching 10% 7 years surgery. Safety assessment of these materials traditionally relies on the use of simple two-dimensional assays, where cells are grown on the surface of the material over a relatively short time frame. It is now well-known that the composition and stiffness of the extracellular matrix (ECM) have a critical effect on cell function. In this work, we have evaluated how cobalt ions influence the assembly of type I collagen, the principle component of the ECM in bone. We found that cobalt had a significant effect on collagen matrix formation, and its presence results in local variations in collagen density. This increase in heterogeneity causes an increase in localized mechanical properties but a decrease in the bulk stiffness of the material. Moreover, when collagen matrices contained cobalt ions, there was a significant change in how the cells interacted with the collagen matrix. Fluorescence images and biological assays showed a decrease in cell proliferation and viability with an increase in cobalt concentration. We present evidence that the cobalt ion complex interacts with the hydroxyl group present in the carboxylic terminal of the collagen fibril, preventing crucial stabilizing bonds within collagen formation. This demonstrates that the currently accepted toxicity assays are poor predictors of the longer-term biological performance of a material.
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http://dx.doi.org/10.1021/acsomega.8b01048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130901PMC
August 2018

Matrix degradation in osteoarthritis primes the superficial region of cartilage for mechanical damage.

Acta Biomater 2018 09 29;78:320-328. Epub 2018 Jul 29.

School of Chemical Engineering, University of Birmingham, Birmingham, UK.

Osteoarthritis (OA) is a degenerative disease that affects 25% of the world's population over fifty years of age. It is a chronic disease of the synovial joints, primarily the hip and knee. The main pathologies are degradation of the articular cartilage and changes to the subchondral bone, as a result of both mechanical wear and a locally elevated inflammatory state. This study compares the viscoelastic properties of cartilage that represents the biochemical changes in OA and age-matched healthy tissue. Further, the mechanical damage induced by this compressive loading cycle was characterised and the mechanism for it was investigated. The storage modulus of OA cartilage was shown to be significantly lower than that of healthy cartilage whilst having a higher capacity to hold water. Following mechanical testing, there was a significant increase in the surface roughness of OA cartilage. This change in surface structure occurred following a reduction in sulphated glycosaminoglycan content of the superficial region in OA, as seen by alcian blue staining and quantified by micro X-ray fluorescence. These findings are important in understanding how the chemical changes to cartilage matrix in OA influence its dynamic mechanical properties and structural integrity.

Statement Of Significance: Cartilage has a very specialised tissue structure which acts to resist compressive loading. In osteoarthritis (OA), there is both mechanically- and chemically-induced damage to cartilage, resulting in severe degradation of the tissue. In this study we have undertaken a detailed mechanical and chemical analysis of macroscopically undamaged OA and healthy cartilage tissue. We have demonstrated, for the first time in human tissue, that the mechanical degradation of the tissue is attributed to a chemical change across the structure. In macroscopically undamaged OA tissue, there is a reduction in the elastic response of cartilage tissue and an associated destabilisation of the matrix that leaves it susceptible to damage. Understanding this allows us to better understand the progression of OA to design better therapeutic interventions.
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http://dx.doi.org/10.1016/j.actbio.2018.07.037DOI Listing
September 2018
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