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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_8 | Pages 15 - 15
10 May 2024
Longoni A Arnold S Major GS Jiang A Wise L Hooper G Kieser D Woodfield T Rnjak-Kovacina J Lim K
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INTRODUCTION

Stimulation of angiogenesis via the delivery of growth factors (GFs) like vascular endothelial growth factor (VEGF) is a promising strategy for the treatment of avascular necrosis (AVN). Tyraminated poly-vinyl-alcohol hydrogels (PVA-Tyr), which have the ability to covalently incorporate GFs, were proposed as a platform for the controlled delivery of therapeutic levels VEGF to the necrotic areas[1]. Nevertheless, PVA hydrophilicity and bioinertness limits its integration with the host tissues. The aim of this study was to investigated the effectiveness of incorporating gelatin, an FDA-approved, non-immunogeneic biomaterial with biological recognition sites, as a strategy to facilitate blood vessels invasion of PVA-Tyr hydrogels and to restore the vascular supply to necrotic tissues.

METHODS

Progressively higher gelatin concentrations (0.01–5wt%) were incorporated in the PVA-Tyr network. Hydrogel physico-chemical properties and endothelial cell attachment were evaluated. Afterwards, the capability of the released VEGF and gelatin to promote vascularization was evaluated via chorioallantoic membrane (CAM) assay. VEGF-loaded PVA-Tyr hydrogels with or without gelatin (n=7) were implanted in a subcutaneous mouse model for 3 weeks. Vascularization (CD31+ cells) and cell infiltration (H&E) were evaluated. Finally, AVN was induced in 6 weeks old male piglets as previously described [2]. A transphyseal hole (3mm) was drilled and PVA-Tyr hydrogels with 1% gelatin were delivered in the defects. Piglets were euthanized after 4 weeks and microCT analysis was performed.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_8 | Pages 37 - 37
10 May 2024
Woodfield T Major G Longoni A Simcock J Hooper G Lim K
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Introduction

Autologous fat grafting has favourable potential as a regenerative strategy and is the current gold-standard to repair large contour defects, as needed in breast reconstruction after mastectomy and traumatic soft tissue reconstruction. Clinically, there is a limit on the volume of lipoaspirate which can be utilised to repair a soft-tissue defect. Surgical complications are the result of poor structural fidelity of lipoaspirate and graft resorption as a filling material and are hindered further by poor graft vascularisation. This study aims to develop injectable lipoaspirate-derived adipose tissue grafts with enhanced biologically and clinically-admissible structural and functional properties adopting light photocrosslinking of unmodified lipoaspirate.

Methods

Patient-derived lipoaspirate was harvested and crosslinked using novel photoinitiator and exposure to visible light (wavelength 450nm) in surgery, establishing bonds between extracellular matrix (ECM) proteins within the material. The degree of crosslinking was tuned (photoinitiator concentration, light exposure, light intensity) and covalent bond formation measured using mass spectrometry. To predict patient response, SWATH-MS was used to identify differences in patient ECM and crosslinked grafts were implanted in vivo using a subcutaneous mouse model. Functional vessel formation and resorption were quantified using micro-CT and tissue-remodelling was assessed via histology.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 29 - 29
4 Apr 2023
Bolam S Konar S Zhu M Workman J Lim K Woodfield T Monk P Coleman B Cornish J Munro J Musson D
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Re-rupture rates after rotator cuff repair remain high because of inadequate biological healing at the tendon-bone interface. Single-growth factor therapies to augment healing at the enthesis have so far yielded inconsistent results. An emerging approach is to combine multiple growth factors over a spatiotemporal distribution that mimics normal healing. We propose a novel combination treatment of insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1) and parathyroid hormone (PTH) incorporated into a controlled-release tyraminated poly-vinyl-alcohol hydrogel to improve healing after rotator cuff repair. We aimed to evaluate this growth factor treatment in a rat chronic rotator cuff tear model.

A total of 30 male Sprague-Dawley rats underwent unilateral supraspinatus tenotomy. Delayed rotator cuff repairs were then performed after 3 weeks, to allow tendon degeneration that resembles the human clinical scenario. Animals were randomly assigned to: [1] a control group with repair alone; or [2] a treatment group in which the hydrogel was applied at the repair site. All animals were euthanized 12 weeks after rotator cuff surgery and the explanted shoulders were analyzed for biomechanical strength and histological quality of healing at the repair site.

In the treatment group had significantly higher stress at failure (73% improvement, P=0.003) and Young's modulus (56% improvement, P=0.028) compared to the control group. Histological assessment revealed improved healing with significantly higher overall histological scores (10.1 of 15 vs 6.55 of 15, P=0.032), and lower inflammation and vascularity.

This novel combination growth factor treatment improved the quality of healing and strength of the repaired enthesis in a chronic rotator cuff tear model. Further optimization and tailoring of the growth factors hydrogel is required prior to consideration for clinical use in the treatment of rotator cuff tears. This novel treatment approach holds promise for improving biological healing of this clinically challenging problem.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 89 - 89
10 Feb 2023
Parker J Lim K Woodfield T Calhaem I Hooper. G
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Hypochlorous acid (HOCl) is a potent anti-bacterial agent which could reduce periprosthetic joint infection. Early infection complications in joint replacements are often considered to be due to local contamination at the time of surgery and result in a significant socioeconomic cost. Current theatre cleaning procedures produce “clean” operating theatres which still contain bacteria (colony forming units, CFU). Reducing this bacterial load may reduce local contamination at the time of surgery. HOCl is produced naturally in the human neutrophil and has been implicated as the primary agent involved in bacterial killing during this process. In vitro research confirms its efficacy against essentially all clinically relevant bacteria. The recent advent of commercial production of HOCl, delivered as a fog, has resulted in extensive use in the food industry. Reported lack of corrosion and high anti-bacterial potency are seen as two key factors for the use of HOCl in the orthopaedic environment. Prior work by the authors comparing human cell toxicity of HOCl, chlorhexidine and iodine solutions shows favourable results.

This study evaluates use of neutral HOCl applied as a dry room fog to decrease bacteria in the operating theatre environment. Using an animal operating theatre as the test site, bacterial swabs were taken from ten 100cm2 sample areas before standard cleaning with detergent, after standard cleaning, and again after 60 minutes exposure to HOCl fog.

After standard cleaning, 6 of 10 sample sites recorded significant bacterial growth (>10 CFU/100cm2). After exposure to HOCl fog, growth in all 10 sites was below detection limits (<10 CFU/100cm2). This was repeated with specific exposure to Staphylococcus aureus and Escherichia coli.

We can conclude that HOCl is effective when used as a fogging agent to reduce bacterial loading within an operating theatre environment and as such has significant potential to reduce intraoperative contamination and periprosthetic infection.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_2 | Pages 4 - 4
1 Mar 2021
Braxton T Lim K Rnjak-Kovacina J Alcala-Orozco C Woodfield T Jiang L Jia X Yang X
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Abstract

Objectives

Assess and characterise the suitability of a novel silk reinforced biphasic 3D printed scaffold for osteochondral tissue regeneration.

Methods

Biphasic hybrid scaffolds consisted of 3D printed poly(ethylene glycol)-terephthalate-poly(butylene terephthalate)(PEGT/PBT) scaffold frame work (pore size 0.75mm), which has been infilled with a cast and freeze dried porous silk scaffold (5×5×2mm3), in addition to a seamless silk top layer (1mm). Silk scaffolds alone were used as controls. Both the biphasic and control scaffolds were characterised via uniaxial compression testing (strain rate 0.1mm/min), and the potential biocompatibility of the scaffolds was tested via in vitro culture of seeded bone marrow stromal cells post fabrication.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 375 - 375
1 Sep 2005
Maffulli N Tallon C Wong J Lim K Bleakney R
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Using a comparative, longitudinal study design, we studied the effects of early weight bearing and ankle mobilisation following acute repair of ruptured Achilles tendon.

Patients in Group 1 (22 males and 4 females; mean age 44.7 years [range 31–69], 11 right- and 15 left-sided ruptures) were immobilised with their ankle in gravity equinus, and encouraged to fully weight bear. They received a single cast change at 2 weeks, when the ankle was accommodated in an anterior splint, allowing full plantarflexion but not dorsiflexion above neutral.

Patients in Group 2 (23 males and 4 females; mean age 43.8 years [range 30–67], 11 right- and 16 left-sided ruptures) were immobilised in full equinus. They received a cast change at 2 and 4 weeks, when the ankle was immobilised in a plantigrade position. They were advised to weight bear 4 weeks after the operation.

Patients in Group 1 attended less outpatient visits and completely discarded their crutches at an average of 2.5 weeks after the operation. Group 2 discarded their crutches at an average of 5.7 weeks after from the operation (p=0.013). At ultrasound scan, the average thickness of the repaired tendon was 12.1 mm (SD 2), with no difference in the thickness of the ruptured tendon regardless of the method of post-operative management. There was no significant difference in isometric strength between the two groups of patients. A greater proportion of patients in Group 1 were satisfied with the results of surgery (p=0.04).

Early weight bearing with the ankle plantigrade is not detrimental to the outcome of repair following rupture of the Achilles tendon, and shortens the time needed for rehabilitation. However, strength deficit and muscle atrophy are not prevented.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 373 - 373
1 Sep 2005
Evans D Lim K Cope S Pereira M Read L
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Introduction Foot surgery has an increased risk of postoperative infection when compared with surgery of other anatomical regions. A pre-surgical foot bath in a bactericidal solution is thought to reduce the incidence of postoperative wound infection. We compared the incidence of post-operative wound infection in two groups, one undergoing a pre-surgical footbath and one group that did not.

Method We prospectively assessed 83 patients undergoing forefoot surgery under the care of two surgical teams. Forty-one patients underwent a pre-surgical foot bath in povidone iodine solution. Forty-two patients did not have a pre-surgical foot bath. All patients had microbiological swabs taken on admission and following surgical preparation and draping. These were cultured for bacterial growth. All patients were reviewed at 2 and 6 weeks after surgery and were monitored for signs of infection. The results for each group were analysed and compared.

Results There were seven post-operative infections in the pre-surgical foot bath group. This compared with only two infections for the group who did not undergo pre-surgical bathing. Correlation of infection with complexity of surgery, medical co-morbidities, operative time, method of closure and use of metalwork was examined.

Conclusions These results suggest that pre-surgical bathing in a bactericidal solution is not effective in preventing post-operative infection.