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.
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. 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].Introduction
Materials and Method
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 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.Background
Patients and Methods
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.
For patients where curative surgery was an option, primary wide local excision (15 patients) or primary amputation (2 patients) was performed. The remaining 2 patients presented with unresectable disease due to the location and localised spread; an embolisation was performed for palliation in both cases. Revision surgery was needed in 9 patients for either a positive resection margin confirmed by histology, or a recurrence; these included 3 secondary amputations. A histologically proven recurrence occurred in 6 patients after an average of 15.8 (4 to 41) months. Local adjuvant radiotherapy was administered to 7 patients and a combination of radio–and chemotherapy was used in 2 patients for metastases. Mortality was 53% (9 patients) by the end of 36 months follow-up period.
The more notable conditions were two synovial sarcomas, three haemangiomas and a Giant cell tumour of the tendon sheath. All patients were treated successfully with complete excision. No recurrences were recorded at the end of 3 year follow-up and all patients were symptom free.
Presented with anterior knee pain. Examination revealed supra-patellar fullness and tenderness. MRI scan showed a suspicious soft tissue tumour. Histology confirmed PVNS after excision biopsy. Presented with medial knee pain, most pronounced after exercise. McMurray test was positive for a meniscal tear. MRI confirmed meniscal tear and additional localised PVNS. The patient underwent repair of the meniscal injury but continued to complain of pain. Following excision of PVNS there was marked improvement in the patients’ symptoms. Presented as massive soft tissue swelling of the right knee. Past medical history included a diagnosis of tuberculosis and fibrosarcoma on the knee. She was referred to our centre following two diagnoses, three surgeries and a supracondylar femoral fracture. The patient was previously advised an above knee amputation which she refused. A repeat biopsy with immunohistochemistry studies at our unit confirmed the diagnosis of a PVNS. Patient is awaiting a total knee replacement with subtotal synovectomy. Presented with swollen right knee, pain and restriction of movement. MRI scan suggested a diagnosis of PVNS. The patient underwent subtotal synovectomy and histology confirmed this to be PVNS. Subsequently the patient had two recurrences, the first at 2 years and later at 4 years from initial surgery. Repeat MRI scan showed extensive third recurrence. The patient is awaiting a further open synovectomy, followed by low dose radiotherapy.
Plasma D-dimer levels were measured as a prerequisite test in all patients before undergoing VQ scan to confirm the absence of PE. All patients had either mechanical, such as foot pumps, or chemical DVT prophylaxis.
The classical triad of dyspnoea, pleuritic chest pain and haemoptysis occurred in only 2 patients. Signs of DVT were present in 3 patients. The electrocardiographs were normal in only 4 patients, though changes particularly suggestive of PE (S1Q3T3, Right bundle branch block or right heart strains) were absent in all of the patients. Chest X-ray changes were of limited value. None showed any of the supposedly characteristic changes. All of the patients had a VQ scan were started on chemical treatment for PE and non of them had definite PE, 12 the patients had probable PE Those patient with probable scan were not subsequently given anticoagulants owing to their medical conditions
Significant complications can occur after sarcoma surgeries. Patient should be adequately informed and educated about the complications Surgeon should properly plan his surgery liaising with other specialities Radical excision offers no significant advantage over wide local excision followed by radiotherapy.
Lymph node involvement is a poor prognostic sign While removal of clinically suspicious lymph nodes is reasonable, there appears to be little justification for treating clinically uninvolved draining regional lymph nodes Therapeutic lymph node dissection might be indicated as part of the palliative management The presence of regional lymph node metastasis at any time should be interpreted as an expression of systemic tumour spread and treated palliatively only.
Although the MRI &
biopsy results in this case were reassuring, the clinical scenario of sudden foot drop with increase in pain point more towards a malignant process rather than a benign condition. Some salient points to differentiate the two include that sarcoma have no history of trauma and the duration of symptoms is longer in haematoma than sarcoma. Also, sarcomas usually involve deeper structures while haematoma occur in superficial layers. It should also be noted that several soft tissue sarcoma themselves commonly reveal haemorrhagic or cystic changes. Other differential diagnosis includes myositis ossificans and tumoral calcinosis.
Relevant literature is reviewed.
In contrast to bony metastases, soft tissue metastases from carcinoma are rare. We reviewed all referrals to our Sarcoma Unit over an eight-year period, and found an incidence of soft tissue metastases from carcinoma of 1.4%. The most common mode of presentation was a painless soft tissue lump in a patient with an occult primary. Lung and kidney were the most frequent primary sources. Overall, prognosis was poor, with a mean survival of 9.4 months. Renal tumours however had a much better prognosis that other types of tumours. Treatment should be individualised according to the underlying disease and the prognosis. Although much rarer than primary soft tissue sarcomas, soft tissue metastases from carcinoma should remain a differential diagnosis in any patient presenting with a suspicious soft tissue lump.
Demographic, diagnostic, clinical, radiological and treatment data was collected on all patients.
All but one patient (Case 6) underwent radiotherapy or chemotherapy or both. Case 6 presented with a soft tissue lump over the shoulder, which on biopsy was found to be metastatic adenocarcinoma of large bowel origin. CT scan of the head confirmed multiple brain metastases. He declined any treatment and died within 2 months of presentation. In total, nine of the ten patients have died of their disease. The mean duration from diagnosis of soft tissue metastasis to death was 9.4 months (range 2–31 months). The duration of survival was significantly better for metastatic carcinoma of the kidney (23 months) compared to the other carcinomas (7 months).
Soft tissue metastases from carcinoma are rare, which again contrasts to bony metastases from carcinoma. Tolia and Whitmore ( Damron and Heiner ( All patients in our series underwent pre-operative MR scans, the appearances of which were not diagnostic of metastases, though highly suggestive of malignancy. Subsequently patients underwent either Tru-cut or open biopsy which gave the definitive diagnosis. As part of the pre-operative work-up, all patients had a CT of the chest and abdominal ultrasound scanning. Rao et al (