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Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 80 - 80
1 Jul 2020
Paul A Basu S Pacelli S Wang J
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A novel injectable hydrogel based on DNA and silicate nanodisks was fabricated and optimized to obtain a suitable drug delivery platform for biomedical applications. Precisely, the hydrogel was designed by combining two different type of networks: a first network (type A) made of interconnections between neighboring DNA strands and a second one (type B) consisting of electrostatic interactions between the silicate nanodisks and the DNA backbone. The silicate nanodisks were introduced to increase the viscosity of the DNA physical hydrogel and improve their shear-thinning properties. Additionally, the silicate nanodisks were selected to modulate the release capability of the designed network.

DNA 4% solutions were heated at 90°C for 45 seconds and cooled down at 37°C degree for two hours. In the second step, the silicate nanodisks suspension in water at different concentrations (0.1 up to 0.5%) were then mixed with the pre-gel DNA hydrogels to obtain the nanocomposite hydrogels. Rheological studies were carried out to investigate the shear thinning properties of the hydrogels. Additionally, the hydrogels were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron microscopy. The hydrogels were loaded with the osteoinductive drug dexamethasone and its release was tested in vitro in phosphate buffer pH 7.4. The drug activity upon release was tested evaluating the osteogenic differentiation of human adipose derived stem cells (hASCs) in vitro through analysis of main osteogenic markers and quantification of alkaline phosphatase activity and calcium deposition. Finally, the hydrogels were tested in vivo and injected into cranial defects in rats to assess their biocompatibility and bone regeneration potential.

The inclusion of the silicate nanodisks increased the viscosity of the hydrogels and the best results were obtained with the highest concentration of the nanoclay (0.5%). The hydrogels possessed shear-thinning properties as demonstrated by cyclic strain sweep tests and were able to recover their original storage modulus G' upon removal of strain. Such improvement in the injectable properties of the formulated hydrogels was mainly attributed to the formation of electrostatic interactions between the silicate nanodisks and the phosphate groups of the DNA backbone as confirmed by XPS analysis of the O, N, and P spectra. Additionally, laponite was able to sustain the release of the osteoinductive drug dexamethasone which was instead completely released from the DNA-based hydrogels after a week. The drug after being released was still active and promoted the osteogenic differentiation of hASCs as confirmed by ALP expression and expression of main osteogenic markers including ALP and COLA1. Finally, the gels proved to be biocompatible in vivo when injected into cranial defects and promoted bone formation at the periphery of the defect after a month post-treatment.

A novel injectable shear-thinning DNA-based hydrogel was characterized and tested for its drug delivery properties. The hydrogel can promote the sustain release of a small molecule like dexamethasone and be biocompatible in vitro and in vivo. Due to these promising findings, the designed system could find also applicability for the delivery of growth factors or other therapeutic molecules.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_1 | Pages 155 - 155
1 Jan 2016
Ghosh R Paul S Rubel YSA Paul A Saha D
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Introduction

Long-term success of the cementless acetabular component has been depends on amount of bone ingrowth around porous coated surface of the implant, which is mainly depends on primary stability, i.e. amount of micromotion at the implant-bone interface. The accurate positioning of the uncemented acetabular component and amount of interference fit (press-fit) at the rim of the acetabulum are necessary to reduce the implant-bone micromotion and that can be enhancing the bone ingrowth around the uncemented acetabular component. However, the effect of implant orientations and amount of press-fit on implant-bone micromotion around uncemented acetabular component has been relatively under investigated. The aim of the study is to identify the effect of acetabular component orientation on implant-bone relative micromotion around cementless metallic acetabular component.

Materials and Method

Three-dimensional finite element (FE) model of the intact and implanted pelvises were developed using CT-scan data [1]. Five implanted pelvises model, having fixed antiversion angle (25°) and different acetabular inclination angle (30°, 35°, 40°, 45° and 50°), were generated in order to understand the effect of implant orientation on implant-bone micromotion around uncemented metallic acetabular component. The CoCrMo alloy was chosen for the implant material, having 54 mm outer diameter and 48 mm bearing diameter [1]. Heterogeneous cancellous bone material properties were assigned using CT-scan data and power law relationship [1], whereas, the cortical bone was assumed homogeneous and isotropic [1]. In the implanted pelvises models, 1 mm diametric press-fit was simulated between the rim of the implant and surrounding bone. Six nodded surface-to-surface contact elements with coefficient of friction of 0.5 were assigned at the remaining portion of the implant–bone interface [1]. Twenty-one muscle forces and hip-joint forces corresponds to peak hip-joint force of a normal walking cycle (13%) were used for the applied loading condition. Fixed constrained was prescribed at the sacroiliac joint and pubis-symphysis [1]. A submodelling technique was implemented, in order to get more accurate result around implant-bone interface [1].


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_27 | Pages 6 - 6
1 Jul 2013
Green C Daniels J Freemont A Paul A
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Background

Although soft tissue sarcoma (STS) is a rare malignancy, myxofibrosarcoma is a common form diagnosed. Myxofibrosarcoma is complicated by a high local recurrence rate (18–54%) and significant morbidity following treatment, hence management can be challenging.

Patients and Methods

Patients treated between 2003–2012 were identified via a database within the histopathology department and case notes were retrospectively assessed. All histology samples were reviewed by a senior histopathologist to ensure a correct diagnosis.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_IV | Pages 43 - 43
1 Mar 2012
Chandrashekar S Hinduja K Paul A Jenkins J
Full Access

Haemangiomas are benign tumours with increased number of normal or abnormal appearing blood vessels. They are the commonest soft tissue tumours of infancy and childhood and comprise 7% of all soft tissue tumours.

Our study is a retrospective analysis of 120 referred cases of various vascular anomalies in the last 10 years. Eighty cases had confirmed haemangiomas. MRI scan and needle biopsy formed the basis of diagnosis. M:F = 42:38. Mean age at presentation was 34.8 years, with the youngest and eldest patient being 3.5 and 78 years respectively. 5 patients were lost to study. Sites of occurrence were upper limb(32), lower limb(32), axilla(3), foot(5), thumb(1), knee(4), spine(1), posterior chest wall(2). 55/80 patients were managed non-operatively by way of Sclerotherapy/Embolisation, watchful observation or symptomatic treatment. 4/55 cases were assessed to be unsuitable for sclerotherapy and 1 patient was subjected to surgery. 6/55 cases did not respond to sclerotherapy. 25/55 cases were managed with surgical excision. Complete excision was the primary goal of surgery. Intralesional margins were accepted if lesions were close to neurovascular structures. Indications for surgery were 1) Pain with functional and/or developmental disturbance, 2) Sudden increase in size, 3) Recurrent haemarthrosis, 4) Failure of sclerotherapy. There were 3 cases of incomplete excision among those operated. 6/25 cases had recurrence 1-8 years after surgery. Mean follow-up was 38.4 weeks (range6-12 months). We have had a success rate of 81.48% with non-operative management of symptomatic haemangiomas. Surgical excision of haemangiomas has borne 76% satisfactory results for pain relief/functional recovery.

We believe that extensive haemangiomata covering large surface areas are not suitable for surgical excision. Majority of cases can be successfully managed non-operatively by way of sclerotherapy/embolisation and watchful observation. MRI scan coupled with trucut needle biopsy has been most successful for diagnosis. Highly vascular sarcomata can mimic haemangiomas, hence histological diagnosis is crucial.