Development and characterization of Polycaprolactone/chitosan-based scaffolds for tissue engineering of various organs: A review.

Research in creating 3D structures mirroring the extracellular matrix (ECM) with accurate environmental cues holds paramount significance in biological applications.Biomaterials that replicate ECM properties-mechanical, physicochemical, and biological-emerge as pivotal tools in mimicking ECM behavior.Incorporating synthetic and natural biomaterials is widely used to produce scaffolds suitable for the intended organs.Polycaprolactone (PCL), a synthetic biomaterial, boasts commendable mechanical properties, albeit with relatively modest biological attributes due to its hydrophobic nature.Chitosan (CTS) exhibits strong biological traits but lacks mechanical resilience for complex tissue regeneration.Notably, both PCL and CTS have demonstrated their application in tissue engineering for diverse types of tissues.Their combination across varying PCL:CTS ratios has increased the likelihood of fabricating scaffolds to address defects in sturdy and pliable tissues.This comprehensive analysis aspires to accentuate their distinct attributes within tissue engineering across different organs.The central focus resides in the role of PCL:CTS-based scaffolds, elucidating their contribution to the evolution of advanced functional 3D frameworks tailored for tissue engineering across diverse organs.Moreover, this discourse delves into the considerations pertinent to each organ.

Does Instrumentation of the Fractured Level in Thoracolumbar Fixation Affect the Functional and Radiological Outcome?

STUDY DESIGN: Retrospective comparative study. OBJECTIVES: To compare radiological and functional outcomes of patients with fixation constructs utilizing pedicle screw stabilization at the fracture level (FL group) versus patients with non-fracture level (NFL group) fixation in single level fractures of the thoracolumbar junction (T11-L1). METHODS: 53 patients of whom fracture level screw was used in 34 (FL group) were compared to 19 patients in NFL group. Radiological parameters analyzed were sagittal index, bi-segmental kyphosis (Cobb) angle and degree of vertebral height restoration. Prospectively collected patient reported functional outcomes and post-operative complications were also studied. Stepwise regression analysis adjusted by age, gender and functional scores was performed to account for the small numbers and unequal sizes of the groups. RESULTS: Back pain score was significantly lower in the FL group (P < 0.025). Core Outcome Measures Index scores and leg pain scores, though low in the FL group, were not statistically significant. The regression analysis showed that the inclusion of the fracture-level screw was independently associated with a greater change in sagittal index and vertebral height restoration post-operatively. Sagittal index was maintained through to final follow up as well. The bi-segmental Cobb's angle correction was not associated with fracture-level screw construct. There was no significant difference between the groups for revision surgery, deep infection, implant failure or length of hospital stay. CONCLUSION: The inclusion of the fracture-level pedicle screws in the fixation construct significantly improves the immediate and final measured radiological parameters, with improved functional scores in single level unstable vertebral fractures of the thoracolumbar junction.

Testing oxygenated microbubbles via intraperitoneal and intrathoracic routes on a large pig model of LPS-induced acute respiratory distress syndrome.

With a mortality rate of 46% before the onset of COVID-19, acute respiratory distress syndrome (ARDS) affected 200,000 people in the US, causing 75,000 deaths. Mortality rates in COVID-19 ARDS patients are currently at 39%. Extrapulmonary support for ARDS aims to supplement mechanical ventilation by providing life-sustaining oxygen to the patient. A new rapid-onset, human-sized pig ARDS model in a porcine intensive care unit (ICU) was developed. The pigs were nebulized intratracheally with a high dose (4 mg/kg) of the endotoxin lipopolysaccharide (LPS) over a 2 h duration to induce rapid-onset moderate-to-severe ARDS. They were then catheterized to monitor vitals and to evaluate the therapeutic effect of oxygenated microbubble (OMB) therapy delivered by intrathoracic (IT) or intraperitoneal (IP) administration. Post-LPS administration, the PaO2 value dropped below 70 mmHg, the PaO2 /FiO2 ratio dropped below 200 mmHg, and the heart rate increased, indicating rapidly developing (within 4 h) moderate-to-severe ARDS with tachycardia. The SpO2 and PaO2 of these LPS-injured pigs did not show significant improvement after OMB administration, as they did in our previous studies of the therapy on small animal models of ARDS injury. Furthermore, pigs receiving OMB or saline infusions had slightly lower survival than their ARDS counterparts. The OMB administration did not induce a statistically significant or clinically relevant therapeutic effect in this model; instead, both saline and OMB infusion appeared to lower survival rates slightly. This result is significant because it contradicts positive results from our previous small animal studies and places a limit on the efficacy of such treatments for larger animals under more severe respiratory distress. While OMB did not prove efficacious in this rapid-onset ARDS pig model, it may retain potential as a novel therapy for the usual presentation of ARDS in humans, which develops and progresses over days to weeks.

Gravity assisted reduction of ankle (GARA) fractures: Results of a novel technique for relocating displaced ankle fractures in the emergency setting in comparison to traditional manipulation and reduction (TMR) technique.

BACKGROUND: Ankle fracture displacements cause significant discomfort to the patient and can compromise soft tissues including the neurovascular structures. Prompt reduction and plaster splint application are vital in the early management of these potentially limb-threatening conditions. The process can be distressing for the patient often requiring additional personnel or equipment. We have used a novel technique of Gravity Assisted Reduction of Ankle (GARA) fractures and compared the results with the Traditional Manipulation and Reduction (TMR) technique. MATERIAL AND METHODS: With adequate analgesia, the patient turns to lay either in lateral or prone position depending on fracture pattern, thus permitting gravity to gradually aid in reduction and hold the fracture in place while Plaster Of Paris (POP) is applied. We performed a retrospective comparative study of GARA vs TMR using validated radiological parameters to assess the quality of reduction with both techniques. RESULTS: 21 patients had GARA technique, in comparison with 19 patients in TMR group. All measured radiological parameters showed similar improvement in both the groups, despite the fact that the pronation-external rotation injury pattern was more often seen in the GARA group. Intravenous sedation and monitoring were needed in 10 patients of TMR group, none in GARA group. On an average 4 personnel needed for TMR, but only 2 personnel needed for GARA technique. CONCLUSION: Gravity assisted ankle fracture reduction is a simple, effective and reproducible alternative technique to TMR, with no need of intravenous sedation along with fewer people needed to perform the procedure. LEVEL OF EVIDENCE: 3b.

Restoration of elective spine surgery during the first wave of COVID-19 : a UK-wide British Association of Spine Surgeons (BASS) prospective, multicentre, observational study.

AIMS: With resumption of elective spine surgery services in the UK following the first wave of the COVID-19 pandemic, we conducted a multicentre British Association of Spine Surgeons (BASS) collaborative study to examine the complications and deaths due to COVID-19 at the recovery phase of the pandemic. The aim was to analyze the safety of elective spinal surgery during the pandemic. METHODS: A prospective observational study was conducted from eight spinal centres for the first month of operating following restoration of elective spine surgery in each individual unit. Primary outcome measure was the 30-day postoperative COVID-19 infection rate. Secondary outcomes analyzed were the 30-day mortality rate, surgical adverse events, medical complications, and length of inpatient stay. RESULTS: In all, 257 patients (128 males) with a median age of 54 years (2 to 88) formed the study cohort. The mean number of procedures performed from each unit was 32 (16 to 101), with 118 procedures (46%) done as category three prioritization level. The majority of patients (87%) were low-medium "risk stratification" category and the mean length of hospital stay was 5.2 days. None of the patients were diagnosed with COVID-19 infection, nor was there any mortality related to COVID-19 during the 30-day follow-up period, with 25 patients (10%) having been tested for symptoms. Overall, 32 patients (12%) developed a total of 34 complications, with the majority (19/34) being grade 1 to 2 Clavien-Dindo classification of surgical complications. No patient required postoperative care in an intensive care setting for any unexpected complication. CONCLUSION: This study shows that safe and effective planned spinal surgical services can be restored avoiding viral transmission, with diligent adherence to national guidelines and COVID-19-secure pathways tailored according to the resources of the individual spinal units. Cite this article: Bone Jt Open 2021;2(12):1096-1101.

Impact of COVID-19 pandemic on acute spine surgery referrals to UK tertiary spinal unit: any lessons to be learnt?

INTRODUCTION: Evidence is emerging, suggesting a significant drop in hospital referrals and attendances for various medical conditions due to the COVID-19 pandemic. With the implementation of lockdown rules, road traffic and outdoor activities were expected to drop, thereby reducing the number of high-energy spinal injuries. Critical non-traumatic spinal conditions like spinal tumours, infections, or compressive pathologies, however, should continue to present as before. We assessed all acute spinal referrals to our tertiary spine unit comparing with the acute activity for a similar time frame in the previous year. The aim was to identify any variance in the acute spinal activity, explain reasons for the discrepancy and identify any learning points. MATERIALS: All acute referrals to our tertiary spinal surgery unit made from 01 February 2020 to 30 April 2020 were evaluated. Similar data from the preceding year, i.e. 2019 was evaluated for comparison. Data were analysed for qualitative or quantitative changes in the referral pattern and their subsequent management outcomes. RESULTS: Spinal referral numbers reduced by 46.05% during the time frame of February-April 2020 when compared to the same period in 2019 (p < 0.017). Similarly, numbers of high-energy traumatic presentations reduced by 72% (p < 0.002). Referrals for critical spinal conditions declined by two-thirds for spinal infections and more than a third for spinal tumours. Emergency surgical workload waned by 27%, especially more so during the six-week lockdown duration. CONCLUSION: Reduction in spinal activity, even for critical spinal conditions, during the pandemic is likely due to a combination of factors like patient behaviour, fear of contracting COVID-19 infection during hospital visit, self-isolation advice, availability of a senior decision maker on the frontlines, and changes in healthcare service provisions. The health crisis may provide an opportunity for optimisation of spinal healthcare services both at the referring hospital and at the tertiary centre.

Vertebral body cemented stents combined with posterior stabilization in the surgical treatment of metastatic spinal cord compression of the thoracolumbar spine.

BACKGROUND: Extensile interventions to provide anterior spinal column support in metastatic spinal cord compression (MSCC) surgery incur added morbidity in this surgically frail group of patients. We present our preliminary results of posterior spinal decompression and stabilization coupled with vertebral body cemented stents for anterior column support in MSCC. METHODS: Fourteen patients underwent posterior spinal decompression and pedicle screw construct along with vertebral body stenting (VBS) technique for reconstruction and augmentation of the vertebral body. The primary in all except one was solid organ malignancy and 10 patients (71%) were treatment naïve. The mean revised Tokuhashi score was 10.7 ± 2.7 and the mean spinal instability neoplastic score was 9.6 ± 1.9. All vertebral body lesions were purely lytic and were associated with a cortical defect in the posterior wall. RESULTS: A mean 5.3 ± 2.7 ml low-viscosity polymethyl methacrylate bone cement was injected within the stent at each compression level. No cement extrusion posteriorly was noted in any case from intraoperative fluoroscopy or postoperative radiographs. Five patients died at a mean 6.8 months (range 1-15 months), while the remaining patients have a mean survival of 18 months. Neither further revision surgical intervention nor any neurological deterioration was noted in any patient, who all continued to be ambulatory. The mean postoperative Core Outcome Measures Index score for 11 patients was 4.03 (standard deviation 3.11, 95% confidence interval (1.93-6.12). CONCLUSION: In lytic vertebral body lesions with posterior wall erosions, cemented VBS technique adds to the surgical armamentarium in MSCC surgery showing promising early results without added complications.

Drug Reaction, Eosinophilia, and Systemic Symptoms (DRESS) Syndrome As a Mimicker of Spinal Infection: Awareness for Spinal Surgeons.

Drug reaction, eosinophilia, and systemic symptoms (DRESS) syndrome is a delayed severe drug hypersensitivity (type IVb) syndrome with cutaneous eruption, hematological abnormalities, and multi-organ involvement. The wide spectrum of the disease manifestations, long-term sequelae, and high mortality rates are a clinical concern. Though not commonly reported in spinal surgery patients, the use of long-term antibiotics is a potential causative agent in spinal infections. DRESS syndrome can mimic systemic spinal infections, and clinical diagnosis requires high awareness and extreme vigilance. Prompt recognition and appropriate action can mitigate the potential poor outcomes and improve patient prognosis.

Clinical Application of Anomalous Muscles for Tendon Transfer in the Upper Limb: A Systematic Review of the Literature.

Numerous anomalous muscles of the forearm and hand have been reported in the literature. The majority were encountered in cadaver dissections and some were incidentally detected during tendon transfer surgery. Because of the limited number of motors available for transfer, it may be advantageous if an anomalous muscle with favorable anatomy can function as a potential donor in a suitable clinical environment. Although several authors have illustrated various anomalies and their functional significance, the reports of actual utilization of such muscles as donors for tendon reconstructions are sparse. The aim of the study is to conduct a systematic review of the clinical applications of anomalous muscles in the upper extremity. After a thorough search of PubMed, Web of Science, Scopus, and Cochrane Library databases, only three out of 106 studies were found to be relevant. Two of them discussed the anomalous radial wrist extensor tendon transfer for thumb flexion. The third study described the usage of anomalous flexor carpi ulnaris (FCU) for thumb opposition and index finger flexion, and also proposed a classification. This is the first systematic review of the clinical application of anomalous muscles as donors in the upper extremity tendon transfer surgical procedures. Knowledge of the above classification helps in intraoperative evaluation of the type of the anomaly and the possible consideration of anomalous muscle as a source of transplant material in an appropriate clinical setting.

Brain Drain: Psychosocial Factors Influence Recovery Following Mild Traumatic Brain Injury-3 Recommendations for Clinicians Assessing Psychosocial Factors.

SYNOPSIS: Mild traumatic brain injury is a major global public health concern. While most people recover within days to months, 1 in 5 people with mild traumatic brain injury report persistent, disabling symptoms that interfere with participation in work, school, and sport. People with injuries to regions other than the head may report similar symptoms. The biopsychosocial model of health explains this phenomenon in terms of factors associated with recovery that are not biomedical. Important psychosocial factors include poor recovery expectations and pretraumatic and posttraumatic psychological symptoms. Recent clinical practice guidelines recommend that clinicians examine all relevant biopsychosocial factors that may contribute to persistent postconcussive symptoms and consider them when helping their patients make health-management decisions. However, because clinical training continues to prioritize biomedical symptoms, clinicians may not feel confident in the psychosocial domain. Our objective is to provide 3 recommendations for clinicians to assess psychosocial factors in patients after concussion, and to argue a case for clinicians to improve their skills in assessing psychosocial factors. J Orthop Sports Phys Ther 2019;49(11):842-844. Epub 1 Jun 2019. doi:10.2519/jospt.2019.8849.

Horseshoe kidney: is there still a debate?

Horseshoe kidneys (HSK) represent an interesting surprise during anatomical dissections directed towards teaching of the urinary system. Clinically, the HSK limits access into the retroperitoneal space due to its location, orientation, and positioning of the ureters. In addition, its highly variable arterial and venous patterns provide great difficulties for surgeons during aortic aneurysm correction, and more recently, HSK transplantation. This case is a morphological study of a noticeably different HSK from the perspective of location, arterial blood supply, and venous drainage, which is further solidified by an embryological review. The debate is opened for further exploration into the theories associated with HSK ascent, its vasculature patterns, and the need for precise diagnostic imaging to serve preoperative planning

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Angiotensin-converting enzyme inhibitor prevents oxidative stress, inflammation, and fibrosis in carbon tetrachloride-treated rat liver.

Hepatic fibrosis is a common feature of chronic liver injury, and the involvement of angiotensin II in such process has been studied earlier. We hypothesized that anti-angiotensin II agents may be effective in preventing hepatic fibrosis. In this study, Long Evans female rats were used and divided into four groups such as Group-I, Control; Group-II, Control + ramipril; Group-III, CCl4; and Group-IV, CCl4 + ramipril. Group II and IV are treated with ramipril for 14 d. At the end of treatment, the livers were removed, and the level of hepatic marker enzymes (aspartate aminotransferase, Alanine aminotransferase, and alkaline phosphatase), nitric oxide, advanced protein oxidation product , catalase activity, and lipid peroxidation were determined. The degree of fibrosis was evaluated through histopathological staining with Sirius red and trichrome milligan staining. Carbon-tetrachloride (CCl4) administration in rats developed hepatic dysfunction and raised the hepatic marker enzymes activities significantly. CCl4 administration in rats also produced oxidative stress, inflammation, and fibrosis in liver. Furthermore, angiotensinogen-inhibitor ramipril normalized the hepatic enzymes activities and improved the antioxidant enzyme catalase activity. Moreover, ramipril treatment ameliorated lipid peroxidation and hepatic inflammation in CCl4-treated rats. Ramipril treatment also significantly reduced hepatic fibrosis in CCl4-administered rats. In conclusion, our investigation suggests that the antifibrotic effect of ramipril may be attributed to inhibition of angiotensin-II mediated oxidative stress and inflammation in liver CCl4-administered rats.

DPP-4 inhibitor sitagliptin prevents inflammation and oxidative stress of heart and kidney in two kidney and one clip (2K1C) rats.

BACKGROUND: Hyperglycemia and insulin resistance often develop cardiovascular and nephrological dysfunction in diabetic patients. Sitagliptin is used to treat diabetes and showed potential benefit in lowering increased blood glucose level in diabetes. This investigation reports the effect of sitagliptin treatment on oxidative stress in kidney and heart of 2K1C rats. METHODS: Male Long Evans rats underwent unilateral surgical stenosis of the renal artery [2-kidney-1-clip (2K1C) method]. These animals entered a 4-weeks dosing period with sitagliptin. Blood and urine sampling and organ harvesting were finally performed. Blood plasma, heart, kidney tissues and urine were tested for the assessment of inflammation and oxidative stress in kidney and heart of 2K1C rats after 4 weeks of surgery. RESULTS: 2K1C rats showed cardiac hypertrophy, increased left ventricular wet weight compared to sham which was not significantly altered by sitagliptin treatment. Uric acid and creatinin concentrations were also increased in 2K1C rats. Sitagliptin significantly prevented the elevation of uric acid and creatinin concentration in plasma and urine in this rat model. Oxidative stress markers in plasma such as malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) concentrations were increased in the 2K1C rats as compared to sham-operated animals. Increased concentrations of these oxidative stress markers were also normalized by sitagliptin treatment. 2K1C rats also showed increased level of uric acid and creatinine both in plasma and urine; which are also reduced to normal level in sitagliptin treated rats. Moreover, 2K1C surgery initiated inflammatory cell infiltration, increased MPO activity and fibrosis in both heart and kidneys which were further ameliorated by sitagliptin treatment. CONCLUSION: Our study suggests that sitagliptin treatment in 2K1C rats prevented inflammation and fibrosis of heart and kidney by ameliorating elevated oxidative stress in heart and kidney tissues.

Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4) Treated Rats.

Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (-)-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4) treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA), nitric oxide, advanced protein oxidation products level (APOP), and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level) and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats.

Supplementation of fresh ucche (Momordica charantia L. var. muricata Willd) prevented oxidative stress, fibrosis and hepatic damage in CCl4 treated rats.

BACKGROUND: Ucche (Momordica charantia L. var. muricata (Willd.) Chakravarty) has been reported to possess many benefits and medicinal properties. However, the protective effect of ucche against carbon tetrachloride (CCl4) induced hepatotoxicity have not been clarified fully yet. The aim of the present study was to investigate the effects of ucche on oxidative stress and inflammation in liver of CCl4 treated rats. METHODS: Female Long Evans rats were administered with CCl4 orally (1 ml/kg) twice a week for 2 weeks and were supplemented with freshly prepared crashed ucche (10% wt/wt of diet) with powdered chaw food. Both plasma and liver tissues were analyzed for AST, ALT and ALP activities. Oxidative stress parameters were measure by determining malondialdehyde (MDA), nitric oxide (NO), advanced protein oxidation product (APOP), and reduced glutathione (GSH) concentrations and catalase activities in plasma and liver tissues. Moreover, inflammation and tissue fibrosis were confirmed by histological staining of liver tissue sections. RESULTS: Our data suggest that ucche significantly prevented CCl4-induced hepatotoxicity, indicated by both diagnostic indicators of liver damage (serum transferases activities) and histopathological analysis. Moreover, CCl4 administration induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing lipid peroxidation level and depletion of antioxidant enzymes in liver. Fresh ucche supplementation prevented the oxidative stresses and improved antioxidant enzyme function. Furthermore, fresh ucche supplementation reduced hepatic inflammatory cell infiltration, iron deposition and fibrosis in liver of CCl4 treated rats. CONCLUSION: In conclusion, these results suggested that the inhibition of CCl4-induced inflammation by ucche is due at least in part to its anti-oxidant activity and its ability to modulate the inflammation and fibrosis in liver.

Antinociceptive and cytotoxic activities of an epiphytic medicinal orchid: Vanda tessellata Roxb.

BACKGROUND: Vanda tessellata (Orchidaceae) has been used in different sorts of ailments such as inflammations, rheumatism, dysentery, bronchitis, dyspepsia and fever in folk medicine. In this study we evaluated the antinociceptive and cytotoxic effect of methanol and aqueous extracts of V. tessellata leaf. METHODS: Oral administration of V. tessellata aqueous (VTA) and methanol (VTM) leaf extracts at 200 and 400 mg/kg body weight (bw) doses were assessed for antinociceptive activity in acetic acid-induced writhing test, hot plate test, and tail immersion test in mice. In this study we also screened for cytotoxicity of the extracts by the brine shrimp (Artemia salina) lethality assay. RESULTS: The extracts, at both doses, exhibited a significant (p < 0.05 - < 0.01) dose-dependent antinociceptive activity in hot plate and tail immersion test. The reaction time was increased to the thermal stimuli at 200 and 400 mg/kg doses up to 90 min. In acetic acid-induced writhing test, oral administration of VTA and VTM (200 and 400 mg/kg) also decreased the writhing significantly while compared to control. The dose 400 mg/kg showed maximum percentage of pain inhibition 42.37% and 45.08% for VTA and VTM respectively. Diclofenac sodium (10 mg/kg) and nalbuphine (10 mg/kg) were used as reference antinociceptive drugs. Very low cytotoxicity was observed on brine shrimps lethality assay. CONCLUSIONS: The leaf extract has potential antinociceptive activity with minimum cytotoxicity. The present study supports the use of V. tessellata in different inflammatory disorders.