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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 7 - 7
2 Jan 2024
Macmillan A Muhammad H Hosni RA Alkhayref M Hotchen A Robertson-Waters E Strangmark E Gompels B Wang J McDonnell S Khan W Clatworthy M Birch M McCaskie A
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In relation to regenerative therapies in osteoarthritis and cartilage repair, mesenchymal stromal cells (MSCs) have immunomodulatory functions and influence macrophage behaviour. Macrophages exist as a spectrum of pro-(M1) and anti-(M2) inflammatory phenotypic subsets. In the context of cartilage repair, we investigated MSC-macrophage crosstalk, including specifically the priming of cartilage cells by macrophages to achieve a regenerative rather than fibrotic outcome. Human monocytes were isolated from blood cones and differentiated towards M1 and M2 macrophages. Monocytes (Mo), M1 and M2 macrophages were cultured directly and indirectly (trans-well system) with human bone marrow derived MSCs. MSCs were added during M1 polarisation and separately to already induced M1 cells. Outcomes (M1/M2 markers and ligands/receptors) were evaluated using RT-qPCR and flow cytometry. Influence on chondrogenesis was assessed by applying M1 and M2 macrophage conditioned media (CM) sequentially to cartilage derived cells (recapitulating an acute injury environment). RT-qPCR was used to evaluate chondrogenic/fibrogenic gene transcription. The ratio of M2 markers (CD206 or CD163) to M1 markers (CD38) increased when MSCs were added to Mo/M1 macrophages, regardless of culture system used (direct or indirect). Pro-inflammatory markers (including TNFβ) decreased. CXCR2 expression by both M1 macrophages and MSCs decreased when MSCs were added to differentiated M1 macrophages in transwell. When adding initially M1 CM (for 12 hours) followed by M2 CM (for 12 hours) sequentially to chondrocytes, there was a significant increase of Aggrecan and Collagen type 2 gene expression and decrease in fibroblastic cell surface markers (PDPN/CD90). Mo/M1 macrophages cultured with MSCs, directly or indirectly, are shifted towards a more M2 phenotype. Indirect culture suggests this effect can occur via soluble signaling mediators. Sequential exposure of M1CM followed by M2CM to chondrocytes resulted in increased chondrogenic and reduced fibrotic gene expression, suggesting that an acute pro-inflammatory stimulus may prime chondrocytes before repair.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 127 - 127
2 Jan 2024
Strangmark E Wang J Hosni RA Muhammad H Alkhrayef M Robertson-Waters E MacMillan A Gompels B Vogt A Khan W Birch M McCaskie A
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Cell culture on tissue culture plastic (TCP) is widely used across biomedical research to understand the in vivo environment of a targeted biological system. However, growing evidence indicates that the characteristics of cells investigated in this way differ substantially from their characteristics in the human body. The limitations of TCP monolayer cell cultures are especially relevant for chondrocytes, the cell population responsible for producing cartilage matrix, because their zonal organization in hyaline cartilage is not preserved in a flattened monolayer assay. Here, we contrast the response of primary human chondrocytes to inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma, via transcriptional, translational, and histological profiling, when grown either on TCP or within a 3D cell pellet (scaffold-less). We focus on anti-apoptotic (Bcl2), pro-apoptotic (Bax, Mff, Fis1), and senescent (MMP13, MMP1, PCNA, p16, p21) markers. We find that the 3D environment of the chondrocyte has a profound effect on the behavior and fate of the cell; in TCP monolayer cultures, chondrocytes become anti-apoptotic and undergo senescence in response to inflammatory cytokines, whereas in 3D cell pellet cultures, they exhibit a pro-apoptotic response. Our findings demonstrate that chondrocyte culture environment plays a pivotal role in cell behavior, which has important implications for the clinical applicability of in vitro research of cartilage repair. Although there are practical advantages to 2D cell cultures, our data suggest researchers should be cautious when drawing conclusions if they intend to extrapolate findings to in vivo phenomena. Our data demonstrates opposing chondrocyte responses in relation to apoptosis and senescence, which appear to be solely reliant on the environment of the culture system. This biological observation highlights that proper experimental design is crucial to increase the clinical utility of cartilage repair experiments and streamline their translation to therapy development.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_16 | Pages 37 - 37
17 Nov 2023
Macmillan A Muhammad H Hosni RA Alkhrayef M Hotchen A Robertson-Waters E Strangmark E Gompels B Wang JH McDonnell S Khan W Clatworthy M Birch M McCaskie A
Full Access

Abstract

Objectives

In relation to regenerative therapies in osteoarthritis and cartilage repair, mesenchymal stromal cells (MSCs) have immunomodulatory functions and influence macrophage behaviour. Macrophages exist as a spectrum of pro-(M1) and anti-(M2) inflammatory phenotypic subsets. In the context of cartilage repair, we investigated MSC-macrophage crosstalk, including specifically the priming of cartilage cells by macrophages to achieve a regenerative rather than fibrotic outcome.

Methods

Human monocytes were isolated from blood cones and differentiated towards M1 and M2 macrophages. Monocytes (Mo), M1 and M2 macrophages were cultured directly and indirectly (trans-well system) with human bone marrow derived MSCs. MSCs were added during M1 polarisation and separately to already induced M1 cells. Outcomes (M1/M2 markers and ligands/receptors) were evaluated using RT-qPCR and flow cytometry. Influence on chondrogenesis was assessed by applying M1 and M2 macrophage conditioned media (CM) sequentially to cartilage derived cells (recapitulating an acute injury environment). RT-qPCR was used to evaluate chondrogenic/fibrogenic gene transcription.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_16 | Pages 57 - 57
17 Nov 2023
Strangmark E Wang JH Hosni RA Muhammad H Alkhrayef M Robertson-Waters E MacMillan A Gompels B Vogt A Khan W Birch M McCaskie A
Full Access

Abstract

BACKGROUND

Cell culture on tissue culture plastic (TCP) is widely used across biomedical research to understand the in vivo environment of a targeted biological system. However, growing evidence indicates that the characteristics of cells investigated in this way differ substantially from their characteristics in the human body. The limitations of TCP monolayer cell cultures are especially relevant for chondrocytes, the cell population responsible for producing cartilage matrix, because their zonal organization in hyaline cartilage is not preserved in a flattened monolayer assay.

OBJECTIVE

Here, we contrast the response of primary human chondrocytes to inflammatory cytokines, tumor necrosis factor-alpha and interferon-gamma, via transcriptional, translational, and histological profiling, when grown either on TCP or within a 3D cell pellet (scaffold-less). We focus on anti-apoptotic (Bcl2), pro-apoptotic (Bax, Mff, Fis1), and senescent (MMP13, MMP1, PCNA, p16, p21) markers.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_16 | Pages 51 - 51
17 Nov 2023
Vogt A Darlington I Brooks R Birch M McCaskie A Khan W
Full Access

Abstract

Objectives

Osteoarthritis is a common articular cartilage disorder and causes a significant global disease burden. Articular cartilage has a limited capacity of repair and there is increasing interest in the use of cell-based therapies to facilitate repair including the use of Mesenchymal Stromal Cells (MSCs). There is some evidence in the literature that suggests that advancing age and gender is associated with declining MSC function, including reduced proliferation and differentiation potential, and greater cellular apoptosis. In our study, we first performed a systematic review of the literature to determine the effects of chronological age and gender on the in vitro properties of MSCs, and then performed a laboratory study to investigate these properties.

Methods and Results

We initially conducted a PRISMA systematic review of the literature to review the evidence base for the effects of chronological age and gender on the in vitro properties of MSCs including cell numbers, expansion, cell surface characterization and differentiation potential. This was followed by laboratory-based experiments to assess these properties. Compare the extent of the effect of age on MSC cell marker expression, proliferation and pathways. Tissue from patients undergoing total knee replacement surgery was used to isolate MSCs from the synovium, fat pad and bone fragments using a method developed in our laboratory. The growth kinetics was determined by calculating the population doublings per day. Following expansion in culture, MSCs at P2 were characterised for a panel of cell surface markers using flow cytometry. The cells were positive for CD73, CD90 and CD105, and negative for antibody cocktail (eg included CD34, CD45). The differentiation potential of the MSCs was assessed through tri-lineage differentiation assays. At P2 after extracting RNA, we investigate the gene analysis using Bulk seq. Clear differences between the younger and older patients and gender were indicated.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 77 - 77
17 Apr 2023
Vogt A Darlington I Birch M Brookes R McCaskie A Khan W
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Osteoarthritis is a common articular cartilage disorder and causes a significant global disease burden. Articular cartilage has a limited capacity of repair and there is increasing interest in the use of cell-based therapies to facilitate repair including the use of Mesenchymal Stromal Cells (MSCs). There is some evidence in the literature that suggests that advancing age is associated with declining MSC function, including reduced proliferation and differentiation potential, and greater cellular apoptosis. In our study, we first performed a systematic review of the literature to determine the effects of chronological age on the in vitro properties of MSCs, and then performed a laboratory study to investigate these properties.

We initially conducted a PRISMA systematic review of the literature to review the evidence base for the effects of chronological age on the in vitro properties of MSCs including cell numbers, expansion, cell surface characterization and differentiation potential. This was followed by laboratory based experiments to assess these properties. Tissue from patients undergoing total knee replacement surgery was used to isolate MSCs from the bone fragments using a method developed in our laboratory. The growth kinetics was determined by calculating the population doublings per day. Following expansion in culture, MSCs at P2 were characterised for a panel of cell surface markers using flow cytometry. The cells were positive for CD73, CD90 and CD105, and negative for CD34 and CD45. The differentiation potential of the MSCs was assessed through tri-lineage differentiation assays. Clear differences between the younger and older patients were indicated.

Chronological age-related changes in MSC function have important implications on the use of these cells in clinical applications for an ageing population. The results from this study will be used to plan further work looking at the effects of chronological age on cellular senescence and identify pathways that could be targeted to potentially reverse any age-related changes.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 111 - 111
11 Apr 2023
Kapetanos K Asimakopoulos D Christodoulou N Vogt A Khan W
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The use of mesenchymal stromal cells (MSCs) in regenerative medicine and tissue engineering is well established, given their properties of self-renewal and differentiation. However, several studies have shown that these properties diminish with age, and understanding the pathways involved are important to provide regenerative therapies in an ageing population.

In this PRISMA systematic review, we investigated the effects of chronological donor ageing on the senescence of MSCs. We identified 3023 studies after searching four databases including PubMed, Web of Science, Cochrane, and Medline. Nine studies met the inclusion and exclusion criteria and were included in the final analyses.

These studies showed an increase in the expression of p21, p53, p16, ROS, and NF- B with chronological age. This implies an activated DNA damage response (DDR), as well as increased levels of stress and inflammation in the MSCs of older donors. Additionally, highlighting the effects of an activated DDR in cells from older donors, a decrease in the expression of proliferative markers including Ki67, MAPK pathway elements, and Wnt/ -catenin pathway elements was observed. Furthermore, we found an increase in the levels of SA- -galactosidase, a specific marker of cellular senescence.

Together, these findings support an association between chronological age and MSC senescence. The precise threshold for chronological age where the reported changes become significant is yet to be defined and should form the basis for further scientific investigations. The outcomes of this review should direct further investigations into reversing the biological effects of chronological age on the MSC senescence phenotype.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 30 - 30
1 Dec 2021
Vogt A Darlington I Brooks R Birch M McCaskie A Khan W
Full Access

Abstract

Osteoarthritis is a common articular cartilage disorder and causes a significant global disease burden. Articular cartilage has a limited capacity of repair and there is increasing interest in the use of cell-based therapies to facilitate repair including the use of Mesenchymal Stromal Cells (MSCs). There is some evidence in the literature that suggests that advancing age is associated with declining MSC function, including reduced proliferation and differentiation potential, and greater cellular apoptosis. In our study, we first performed a systematic review of the literature to determine the effects of chronological age on the in vitro properties of MSCs, and then performed a laboratory study to investigate these properties. We initially conducted a PRISMA systematic review of the literature to review the evidence base for the effects of chronological age on the in vitro properties of MSCs including cell numbers, expansion, cell surface characterization and differentiation potential. This was followed by laboratory based experiments to assess these properties. Tissue from patients undergoing total knee replacement surgery was used to isolate MSCs from the infrapatellar fat pad using a method developed in our laboratory. The growth kinetics was determined by calculating the population doublings per day. Following expansion in culture, MSCs at P2 were characterised for a panel of cell surface markers using flow cytometry. The cells were positive for CD73, CD90 and CD105, and negative for CD34 and CD45. The differentiation potential of the MSCs was assessed through tri-lineage differentiation assays. Chronological age-related changes in MSC function have important implications on the use of these cells in clinical applications for an ageing population. The results from this study will be used to plan further work looking at the effects of chronological age on cellular senescence and identify pathways that could be targeted to potentially reverse any age-related changes.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 14 - 14
1 Dec 2021
Darlington I Vogt A Williams EC Brooks R Birch M Mohorianu I Khan W McCaskie A
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Abstract

Focal articular cartilage defects do not heal and, left untreated, progress to more widespread degenerative changes. A promising new approach for the repair of articular cartilage defects is the application of cell-based regenerative therapies using mesenchymal stromal cells (MSCs). MSCs are however present in a number of tissues and studies suggest that they vary in their proliferation, cell surface characterisation and differentiation. As the phenotypic properties of MSCs vary depending on tissue source, a systematic comparison of the transcriptomic signature would allow a better understanding of these differences between tissues, and allow the identification of markers specific to a MSC source that is best suited for clinical application. Tissue was used from patients undergoing total knee replacement surgery for osteoarthritis following ethical approval and informed consent. MSCs were isolated from bone, cartilage, synovium and infrapatellar fat pad. MSC number and expansion were quantified. Following expansion in culture, MSCs were characterised using flow cytometry with several cell surface markers; the cells from all sources were positive for CD44, CD90 and CD105. Their differentiation potential was assessed through tri-lineage differentiation assays. In addition, bulk mRNA-sequencing was used to determine the transcriptomic signatures. Differentially expressed (DE) genes were predicted. An enrichment analysis focused on the DE genes, against GO and pathway databases (KEGG and Reactome) was performed; protein-protein interaction networks were also inferred (Metascape, Reactome, Cytoscape). Optimal sourcing of MSCs will amplify their cartilage regeneration potential. This is imperative for assessing future therapeutic transplantation to maximise the chance of successful cartilage repair. A better understanding of differences in MSCs from various sources has implications beyond cartilage repair.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 45 - 45
1 Dec 2021
Lu V Tennyson M Zhang J Khan W
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Abstract

Objectives

Tendon and ligament injury poses an increasingly large burden to society. With surgical repair and grafting susceptible to high failure rates, tissue engineering provides novel avenues for treatment. This systematic review explores in vivo evidence whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can facilitate tendon and ligament repair in animal models.

Methods

On May 26th 2021, a systematic search was performed on PubMed, Web of Science, Cochrane Library, Embase, using search terms ‘mesenchymal stem cell’ or ‘multipotent stem cell’ AND ‘extracellular vesicles’ or ‘exosomes’ AND ‘tendon’ or ‘ligament’ or ‘connective tissue’. Risk of bias was assessed using SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) tool. Studies administering EVs isolated from human or animal-derived MSCs into in vivo models of tendon/ligament injury were included. In vitro, ex vivo, in silico studies were excluded, and studies without a control group were excluded. Data on isolation and characterisation of MSCs and EVs, and in vivo findings in animal models were extracted.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_16 | Pages 5 - 5
1 Dec 2021
Agarwal N Mak CC Bojanic C To K Khan W
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Abstract

Osteoarthritis (OA) is a degenerative disorder associated with cartilage loss and is a leading cause of disability around the world. In old age, the capacity of cartilage to regenerate is diminished. With an aging population, the burden of OA is set to rise. Currently, there is no definitive treatment for OA. However, cell-based therapies derived from adipose tissue are promising. A PRISMA systematic review was conducted employing four databases (MEDLINE, EMBASE, Cochrane, Web of Science) to identify all clinical studies that utilized adipose tissue derived mesenchymal stem cells (AMSCs) or stromal vascular fraction (SVF) for the treatment of knee OA. Eighteen studies were included, which met the inclusion criteria. Meta-analyses were conducted on fourteen of these studies, which all documented WOMAC scores after the administration of AMSCs. Pooled analysis revealed that cell-based treatments definitively improve WOMAC scores, post treatment. These improvements increased with time. The studies in this meta-analysis have established the safety and efficacy of both AMSC therapy and SVF therapy for knee OA in old adults and show that they reduce pain and improve knee function in symptomatic knee OA suggesting that they may be effective therapies to improve mobility in an aging population.


Bone & Joint Open
Vol. 2, Issue 4 | Pages 261 - 270
1 Apr 2021
Hotchen AJ Khan SA Khan MA Seah M Charface ZH Khan Z Khan W Kang N Melton JTK McCaskie AW McDonnell SM

Aims

To investigate factors that contribute to patient decisions regarding attendance for arthroplasty during the COVID-19 pandemic.

Methods

A postal questionnaire was distributed to patients on the waiting list for hip or knee arthroplasty in a single tertiary centre within the UK. Patient factors that may have influenced the decision to attend for arthroplasty, global quality of life (QoL) (EuroQol five-dimension three-level (EQ-5D-3L)), and joint-specific QoL (Oxford Hip or Knee Score) were assessed. Patients were asked at which ‘COVID-alert’ level they would be willing to attend an NHS and a “COVID-light” hospital for arthroplasty. Independent predictors were assessed using multivariate logistic regression.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_2 | Pages 3 - 3
1 Mar 2021
To K Zhang B Romain K Mak CC Khan W
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Abstract

Objective

Articular cartilage damaged through trauma or disease has a limited ability to repair. Untreated, these focal lesions progress to generalized changes including osteoarthritis. Musculoskeletal disorders including osteoarthritis are the most significant contributor to disability globally. There is increasing interest in the use of mesenchymal stem cells (MSCs) for the treatment of focal chondral lesions. There is some evidence to suggest that the tissue type from which MSCs are harvested play a role in determining their ability to regenerate cartilage in vitro and in vivo. In humans, MSCs derived from synovial tissue may have superior chondrogenic potential.

Methods

We carried out a systematic literature review on the effectiveness of synovium-derived MSCs (sMSCs) in cartilage regeneration in in vivo studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Nineteen studies were included in our review; four examined the use of human sMSCs and the remainder were conducted using sMSCs harvested from animals.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_2 | Pages 11 - 11
1 Mar 2021
Mak CC To K Fekir K Brooks R Khan W
Full Access

Abstract

Objective

SOX genes comprise a family of transcription factors characterised by a conserved HMG-box domain that confer pleiotropic effects on cell fate and differentiation through binding to the minor groove of DNA. Paracrine regulation and contact-dependant Notch signalling has been suggested to modulate the induction of SOX gene expression. The objective of this study is to investigate the crosstalk between mesenchymal stromal cells (MSCs) and chondrocytes by comparing SOX gene expression in their co-culture and respective monocultures.

Methods

Our study adopted an in vitro autologous co-culture of p0 adipose-derived MSCs (AMSCs) and articular chondrocytes derived from Kellgren-Lawrence Grade III/IV osteoarthritic knee joints (n=7). Cells were purified and co-cultured with one AMSC for every chondrocyte at 5000 cells/cm2. The AMSCs were characterised by a panel of MSC surface markers in flow cytometry and were allowed to undergo trilineage differentiation for subsequent histological investigation. SOX5, SOX6, and SOX9 expression of co-cultures and monoculture controls were quantified by TaqMan quantitative real-time PCR. Experiments were performed in triplicate.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 9 - 9
1 Mar 2021
To K Khan W
Full Access

The current standard of practice following knee arthroplasty is to demonstrate the appropriate alignment of knee replacements using knee radiographs. Recent studies have suggested that standard knee radiographs provide adequate accuracy for tibial prosthesis alignment assessment as compared with long knee view radiographs which are more technically demanding and carry greater radiation exposure. In this study, we aim to address whether alignment measured on standard knee radiographs are reliable and reproducible over time.

We examined a cohort of 80 patients 37 male (46%), 43 females (54%), mean age = 68 years) who underwent total knee arthroplasty (TKA). Standard knee anteroposterior radiographs performed within 2 days following surgery were compared to standard knee anteroposterior radiographs taken 1 year following the surgery in patients with well-functioning prosthesis. Tibial prosthesis alignment angles between the longitude of the tibial shaft and the tibial baseplate were calculated using Centricity Enterprise Web V3.0 software. The data was examined using R software.

In well-functioning primary knee arthroplasties, tibial prosthesis alignment angles measured in the 1-year follow-up standard view knee radiographs were found to deviate from measurements obtained with the same radiographic specifications in the immediate post-operative period. A significant mean percentage difference was found between the two radiographs.

Long knee view radiographs may be required in order to accurately assess tibial prothesis alignment following total knee arthroplasty.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 10 - 10
1 Mar 2021
To K Khan W Marway P
Full Access

Companies manufacturing total knee arthroplasty (TKA) prostheses produce a variety of tibial and femoral components of different dimensions denoted by numbers or letters. Surgeons frequently implant components that are compatible but not of the same size on the femur and tibia. Recent studies suggest that equally sized femoral and tibial components produce better outcomes compared to size-mismatched components. In our study, we aim to explore the relationship between component size and outcome measured by oxford knee score at six weeks and one year following TKA.

A cohort of twenty-four patients who underwent TKA and had well-functioning prosthesis were studied. Thirteen (54%) had equally sized TKA components implanted, seventy-four patients (42%) had components that were mismatched by one size, and one (4%) had components that were mismatched by more than one size. The Oxford Knee Score (OKS) obtained preoperatively, at six weeks and one year postoperatively were retrieved from an electronic database. All data were analysed using R software.

A significant improvement in pre-operative and one-year postoperative OKS was observed. Patients who received one-size mismatched tibial and femoral components demonstrated a less pronounced improvement in OKS as compared with patients who received equally sized components.

When possible, it may be best to utilise equally sized prosthetic tibial and femoral components when performing total knee arthroplasty. Manufacturers may be able to produce better patient outcomes by including prostheses that are between sizes as part of their production line.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_2 | Pages 13 - 13
1 Mar 2021
Mak CC To K Fekir K Brooks R Khan W
Full Access

Abstract

Objective

Mesenchymal stem cells (MSCs) and chondrocytes have both been crucial in trials for cartilage repair, and there has been growing interest into their respective secretomes owing to their role in chondrogenic crosstalk. This has been studied by in vitro co-culture studies, yet the optimal ratio of seeding MSCs in co-culture has been understudied.

Methods

Our study utilised an in vitro autologous co-culture of p0 adipose-derived MSCs (AMSCs) and articular chondrocytes derived from Kellgren-Lawrence Grade III/IV osteoarthritic knee joints (n=5). To investigate whether a large proportion of MSCs could be stimulated by a small number of chondrocytes, we seeded these MSCs at increasing logarithmic ratios to the number of chondrocytes at 1:1, 10:1, and 100:1. The AMSCs were phenotyped by a panel of MSC surface markers in flow cytometry, and allowed to undergo trilineage differentiation. Gene expression following in vitro co-culture was quantified by RT-qPCR with a panel comprising COL1A1, COL2A1, COL10A1, L-SOX5, SOX6, SOX9, ACAN, HSPG2, and COMP for chondrogenesis. Experiments were performed in triplicate.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 69 - 69
1 Dec 2015
Williams R Kotwal R Roberts-Huntley N Khan W Morgan-Jones R
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At first-stage revision surgery for infection of total knee arthroplasties, antibiotic-impregnated cement spacers are frequently implanted. Two types of cement spacers are commonly used, “static” and “articulating” cement spacers. Advocates of cement spacers state that they deliver high doses of antibiotics locally, increase patient comfort, allow mobility and provide joint stability. They also minimize contracture of collateral ligaments, thereby facilitating re-implantation of a definitive prosthesis at a later stage. The use of these cement spacers, however, are not without significant complications, including patella tendon injuries.

We describe a series of three patients who sustained patella tendon injuries in infected total knee arthroplasties following the use of a static cement spacer at first-stage knee revision.

The patella tendon injuries resulted in significant compromise to wound healing and knee stability requiring multiple surgeries. The mid-term function was poor with an Oxford score at 24 months ranging from 12–20

Based on our experience, we advise caution in the use of static cement spacer blocks. If they are to be used, we recommend that they should be keyed in the bone to prevent patella tendon injuries.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_15 | Pages 66 - 66
1 Dec 2015
Khan W Williams R Metah A Morgan-Jones R
Full Access

Honey has been used as a topical antiseptic for at least 5,000 years. SurgiHoney is a CE licensed sterile product, which has been proven to be non-toxic and effective when used topically in the treatment of chronically infected wounds. The key difference from other medical grade honey is the broad spectrum antimicrobial characteristics with activity against Gram +ve, Gram –ve and multi-resistant organisms. Its novel role against the bacterial bioburden and biofilm associated with periprosthetic infections around total knee arthroplasties (TKA's) is therefore considered.

SurgiHoney was used as an implant coating immediately prior to wound closure after implantation of salvage endoprosthesis for multiply revised, infected TKA's undergoing staged reconstruction.

We report a consecutive series of multi-revised, infected revision TKA's where SurgiHoney was used as an active antimicrobial coating. We discuss its intra-operative application and early clinical outcomes.

The use of Surgihoney as a novel anti-microbial is established in the management of complex wound infections. This is the first reported use of SurgiHoney as a deep, implant coating in the salvage of prosthetic joint infection.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 64 - 64
1 Dec 2015
Williams R Khan W Huntley N Morgan-Jones R
Full Access

Joint degeneration may make a total knee arthroplasty (TKA) a requirement for pain relief and function. However, the presence of ipsilateral limb osteomyelitis (OM) makes surgical management extremely challenging.

We report the experience of a high volume revision knee surgeon managing ipsilateral limb multi resistant OM and the outcome of subsequent TKA.

Four consecutive patients were identified who had either ipsilateral femoral or tibial chronic osteomyelitis treated prior to undergoing TKA. Surgery to eradicate the osteomyelitis involved a Lautenbach compartmental debridement, and where necessary, healing by secondary intention. The decision to proceed to a TKA was based on history, clinical examination and radiological findings of advanced osteoarthritic change.

The patients had a mean age of 50 years. They had a background of multi-organism OM and underwent single-stage TKAs at an average of 63 months following eradication of the underlying OM.

Three patients did well but had complications associated with poor skin and soft tissues, and abnormal bone anatomy. One patient developed an infection and following a re-revision had an arthrodesis.

The results for the four cases are summarised in Table 1.

We have highlighted that patients with ipsilateral limb multi resistant OM are a difficult cohort to manage.