Emerging Advances in Nanocarriers Approaches in the Effective Therapy of Pain Related Disorders: Recent Evidence and Futuristic Needs.

Pain disorders are the primary cause of disability nowadays. These disorders, such as rheumatoid arthritis (RA) and osteoarthritis (OA), cause loss of function, joint pain and inflammation and deteriorate the quality of life. The treatment of these inflammatory diseases includes anti-inflammatory drugs administered via intra-articular, topical or oral routes, physical rehabilitation or surgery. Owing to the various side effects these drugs could offer, the novel approaches and nanomaterials have shown potential to manage inflammatory diseases, prolonged half-life of anti-inflammatory drugs, reduced systemic toxicity, provide specific targeting, and refined their bioavailability. This review discusses in brief about the pain pathophysiology and its types. The review summarizes the conventional therapies used to treat pain disorders and the need for novel strategies to overcome the adverse effects of conventional therapies. The review describes the recent advancements in nanotherapeutics for inflammatory diseases using several lipids, polymers and other materials and their excellent efficiency in improving the treatment over conventional therapies. The results of the nanotherapeutic studies inferred that the necessity to use nanocarriers is due to their controlled release, targeting drug delivery to inflamed tissues, low toxicity and biocompatibility. Therefore, it is possible to assert that nanotechnology will emerge as a great tool for advancing the treatment of pain disorders in the near future.

Organoids: A new approach in toxicity testing of nanotherapeutics.

Nanotechnology has revolutionized diverse fields, which include agriculture, the consumer market, medicine, and other fields. Widespread use of nanotechnology-based products has led to increased prevalence of these novel formulations in the environment, which has raised concerns regarding their deleterious effects. The application of nanotechnology-based formulations into clinical use is hampered by the lack of the availability of effective in vitro systems, which could accurately assess their in vivo toxic effects. A plethora of studies has shown the hazardous effects of nanoparticle-based formulations in two-dimensional in vitro cell cultures and animal models. These have some associated disadvantages when used for the evaluation of nano-toxicity. Organoid technology fills the space between existing two-dimensional cell line culture and in vivo models. The uniqueness of organoids over other systems for evaluating toxicity caused by nano-drug formulation includes them being a co-culture of diverse cell types, dynamic flow within them that simulates the actual flow of nanoparticles within biological systems, extensive cell-cell, cell-matrix interactions, and a tissue-like morphology. Thus, it mimics the actual tissue microenvironment and, subsequently, provides an opportunity to study drug metabolism and toxico-dynamics of nanotechnology-based novel formulations. The use of organoids in the evaluation of nano-drug toxicity is in its infancy. A limited number of studies conducted so far have shown good predictive value and efficiently significant data correlation with the clinical trials. In this review, we attempt to introduce organoids of the liver, lungs, brain, kidney intestine, and potential applications to evaluate toxicity caused by nanoparticles.

Knee Arthrodesis Using Dual-Plate Construct is Following Failed Distal Femur Megaprosthesis-A Case Report.

Introduction: Knee arthrodesis following failed total knee arthroplasty is a viable limb salvage option, and this procedure is reserved for failed two-stage revision surgery in severe comorbid patients with irreparable extensor mechanism disruption, severe instability, and extensive soft tissue loss. Knee arthrodesis using a dual-plate construct has been scarcely reported. We report a case of knee arthrodesis using a dual-plate construct in a male in his 20s who presented to us with a broken distal femur megaprosthesis. Case Report: An anterior midline incision was given. The cement mantle and broken prosthetic components were removed. The bone surfaces were freshened up and fixed using two orthogonal locking plates. After 4 months, there was a solid fusion in the knee, and the patient started walking independently with a short limb gait. The patient was advised limb lengthening for a shortening of 3 cm, but he denied it and managed with a shoe raise. After 4 years, he was pain free, and radiographs revealed a solid knee fusion. The patient was fully satisfied with the procedure, and he resumed manual work. Conclusion: This case report revealed that knee arthrodesis using a dual-plate construct is an economically viable salvage option for failed distal femur megaprosthesis.

Primary Aneurysmal Bone Cyst in the Iliac Bone: A Case Report.

Introduction: Aneurysmal bone cysts (ABCs) are non-neoplastic expansile, vascular, osteolytic benign tumors in the long bone, spine, and sternum. The location in the pelvis is sparse. Case Report: A 12-year-old female presented with pain in her left pelvis for 6 months. On radiological examination, we found an expansile balloting lytic lesion involving almost the whole ilium and sparing the hip joint. There were multiple fluid levels seen on magnetic resonance imaging. The initial biopsy suggested ABC. Curettage and bone grafting were done along with electrocauterization and chemical cauterization. At 1-year follow-up, she is doing well without any complaints. Conclusion: This case report demonstrates a rare ABC of the ilium that was managed with curettage and bone grafting.

Chondroprotective Effects of a Single PRP Injection in a Spontaneous Osteoarthritis Model of Dunkin Hartley Guinea Pig: An Immunohistochemical Analysis.

Purpose of the Study: The evaluation of anti-apoptotic and chondroprotective properties of a single injection of PRP using immunohistochemistry (IHC). Methods: This was a placebo-controlled blinded experimental study. Ten healthy Dunkin Hartley guinea pigs were selected. One knee of each animal was injected with a single injection of PRP (Group A); the contralateral knee acted as a control and was injected with a single injection of normal saline (Group B). These groups were further divided into A3 and B3 based on the timeline of animal sacrifice (3 months) and A6 and B6 (6 months). The formalin-preserved articular cartilage blocks were subjected to IHC to stain Aggrecan, Caspase-3, and Collagen-2. Results: The mean IHC score was significantly low for Caspase-3 (p-0.029) in intervention group (A3) in comparison to placebo control group (B3) pointing towards decreased apoptosis. The mean IHC values were significantly higher for Collagen II (p-0.011) for intervention group (A6) in contrast to control group (B6); values were also significantly low for Caspase-3 (p-0.029) in A6 as compared to B6. The mean Caspase-3 values were significantly higher in A6 as compared to A3 (p-0.029). Conclusion: The impact of a solitary injection of PRP on upregulation of anabolic pathways inside cartilage is relatively slower as compared to its effect on downregulation of apoptotic pathways. Even a single PRP injection holds the potential to change cartilage microenvironment, but the effects are not long lasting.

Nanoengineered oxygen-releasing polymeric scaffold with sustained release of dexamethasone for bone regeneration.

Maintaining the continuous oxygen supply and proper cell growth before blood vessel ingrowth at the bone defect site are considerably significant issues in bone regeneration. Oxygen-producing scaffolds can supply oxygen and avoid hypoxia leading to expedited bone regeneration. Herein, first oxygen-producing calcium peroxide nanoparticles (CPO NPs) are synthesized, and subsequently, the various amounts of synthesized CPO NPs (0.1, 0.5, and 1 wt/v%) loaded in the scaffold composite, which is developed by simple physical blending of chitosan (CS) and polycaprolactone (PCL) polymers. To deliver the synergistic therapeutic effect, dexamethasone (DEX), known for its potential anti-inflammatory and osteogenic properties, is loaded into the nanocomposite scaffolds. The extensive physicochemical characterizations of nanocomposite scaffolds confirm the successful loading of CPO NPs, adequate porous morphology, pore size, hydrophilicity, and biodegradability.In vitro, biological studies support the antibacterial, hemocompatible, and cytocompatible (MG-63 and MC3T3-E1 cells) nature of the material when tested on respective cells. Field emission scanning electron microscopy and energy-dispersive x-ray spectroscopy confirm the successful biomineralization of the scaffolds. Scaffolds also exhibit the sustained release of DEX and efficient protein adsorption. This study revealed that a nanoengineered scaffold loaded with CPO NPs (PCL/CS/DEX/CPO 3) is a suitable candidate for bone tissue regeneration.

A comparative study of perioperative pain, blood loss, and hospital stay in an Indian population undergoing mini-open oblique lumbar interbody fusion versus open transforaminal lumbar interbody fusion.

Background: There are several approaches for lumbar fusion, although there is yet to be a consensus on which approach is the best. This study aimed to evaluate the intraoperative blood loss and acute postoperative pain in single-level mini-open oblique lumbar interbody fusion (OLIF) versus open transforaminal lumbar interbody fusion (TLIF) surgeries for the degenerative spine. Methods: Thirty-two patients were assigned by the surgeon to OLIF or TLIF groups - 16 in mini-open OLIF and 16 in open TLIF groups. The intraoperative blood loss and postoperative hemoglobin, numerical rating scale (NRS) at proposed time intervals for 24 h postoperative, and rescue analgesics used were compared among the groups. The operative duration and hospital stay in both groups were also compared. Results: The OLIF group showed significantly higher postoperative hemoglobin (11.5 vs. 10.5 g %, P = 0.04), lower 24-h postoperative pain scores on movement, (NRS 4 vs. 5.5, P = 0.0001), and shorter hospital stay (4.5 vs. 7 days, P = 0.003) than TLIF group. However, the surgery duration was significantly longer in OLIF than in TLIF (190 vs. 150 min, P = 0.005). Intraoperative hemodynamics, other postoperative pain scores at variable time points, and rescue analgesics given were comparable among groups (P > 0.05). Intraoperative blood loss was lower in OLIF than TLIF (275 vs. 500 mL) but was not statistically significant (P > 0.05). Conclusion: Mini-open OLIF has favorable perioperative outcomes compared to open TLIF. Patients have higher postoperative hemoglobin and lesser pain on movement on the first postoperative day, leading to earlier mobilization and a shorter hospital stay.

Technological Interventions Enhancing Curcumin Bioavailability in Wound-Healing Therapeutics.

Wound healing has been a challenge in the medical field. Tremendous research has been carried out to expedite wound healing by fabricating various formulations, some of which are now commercially available. However, owing to their natural source, people have been attracted to advanced formulations with herbal components. Among various herbs, curcumin has been the center of attraction from ancient times for its healing properties due to its multiple therapeutic effects, including antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, neuroprotective, and radioprotective properties. However, curcumin has a low water solubility and rapidly degrades into inactive metabolites, which limits its therapeutic efficacy. Henceforth, a carrier system is needed to carry curcumin, guard it against degradation, and keep its bioavailability and effectiveness. Different formulations with curcumin have been synthesized, and exist in the form of various synthetic and natural materials, including nanoparticles, hydrogels, scaffolds, films, fibers, and nanoemulgels, improving its bioavailability dramatically. This review discusses the advances in different types of curcumin-based formulations used in wound healing in recent times, concentrating on its mechanisms of action and discussing the updates on its application at several stages of the wound healing process. Impact statement Curcumin is a herbal compound extracted from turmeric root and has been used since time immemorial for its health benefits including wound healing. In clinical formulations, curcumin shows low bioavailability, which mainly stems from the way it is delivered in the body. Henceforth, a carrier system is needed to carry curcumin, guard it against degradation, while maintaining its bioavailability and therapeutic efficacy. This review offers an overview of the advanced technological interventions through tissue engineering approaches to efficiently utilize curcumin in different types of wound healing applications.

Multicomponent decellularized extracellular matrix of caprine small intestine submucosa based bioactive hydrogel promoting full-thickness burn wound healing in rabbits.

Effective treatment for full-thickness burn wounds has remained challenging for clinicians. Among various strategies, extracellular gel-based dressing materials have gained attention to promote effective and rapid wound healing. These gel-based materials are porous and have antioxidant, antibacterial, hydrophilic, biodegradation, and biocompatible properties and hence can be used to alleviate burn wound healing. In concurrence with these findings, the present study evaluates thermo-responsive and self-assembled decellularized extracellular matrix (ECM) of caprine small intestine submucosa (DG-SIS) gel-based dressing material for burn wound healing. To expedite healing and efficiently tackle excessive free radicals and bioburden at the burn wound site, DG-SIS gel is fortified with antibacterial components (zinc oxide nanoparticles; ZnO) and a potent antioxidant agent (Vitamin-C;Vt-C). ZnO- and Vt-C-enriched DG-SIS (DG-SIS/ZnO/Vt-C) gels significantly increased the antioxidant and antibacterial activity of the therapeutic hydrogel. Additionally, the fabricated DG-SIS/ZnO/Vt-C bioactive gel resulted in significant full-thickness burn wound contraction (97.75 % in 14 days), a lower inflammatory effect, and enhanced angiogenesis with the highest collagen synthesis (1.22 µg/mg in 14 days) at the wound site. The outcomes from this study demonstrate a synergistic effect of ZnO/Vt-C in the bioactive gel as an effective and inexpensive therapeutic approach for full-thickness burn wound treatment.

A novel technique of reconstruction of the distal tibia using allograft after resection of giant cell tumor: A case report with literature review.

Giant cell tumor (GCT) of the distal tibia can result in significant bone loss and soft tissue compromise, which can present a challenge for reconstruction. Various techniques have been described for the reconstruction of large defects, including the use of allografts. In this article, we describe a novel technique of reconstruction of a large defect in the distal tibia using two femoral head allografts after resection of GCT. The technique involves using two femoral head allografts, which are shaped to fit the defect and secured with a locking plate and screws. Using this technique, we present a case report of a patient with GCT of the distal tibia who underwent resection and reconstruction. At the 18-month follow-up, the patient had good functional outcomes and no evidence of tumor recurrence. This technique offers a viable option for reconstructing large defects in the distal tibia after GCT resection, particularly in cases where autograft is not available or not feasible. Further studies are needed to evaluate the long-term outcomes and complications associated with this technique.

Meropenem loaded 4-arm-polyethylene-succinimidyl-carboxymethyl ester and hyaluronic acid based bacterial resistant hydrogel.

Developing an ideal vitreous substitute/implant is a current challenge. Moreover, implants (e.g., heart valves and vitreous substitutes), are associated with a high risk of bacterial infection when it comes in contact with cells at implant site. Due to infection, many implants fail, and the patient requires immediate surgery and suffers from post-operative problems. To overcome these problems in vitreous implants, we developed a bacterial resistant vitreous implant, where meropenem (Mer), an antibiotic, has been incorporated in a hydrogel prepared by crosslinking HA (deacetylated sodium hyaluronate) with 4-arm-polyethylene-succinimidyl-carboxymethyl-ester (PESCE). The HA-PESCE hydrogel may serve as a suitable artificial vitreous substitute (AVS). The pre-gel solutions of HA-PESCE without drug and with the drug are injectable through a 22 G needle, and the gel formation occurred in approx. 3 min: it indicates its suitability for in-situ gelation through vitrectomy surgery. The HA-PESCE hydrogel depicted desired biocompatibility, transparency (>90 %), water content (96 %) and sufficient viscoelasticity (G' >100 Pa) calculated after 1 month in-vitro, which are suitable for vitreous substitute. The HA-Mer-PESCE hydrogel showed improved biocompatibility, suitable transparency (>90 %), high water content (96 %), and suitable viscoelasticity (G' >100 Pa) calculated after 1 month in-vitro, which are suitable for vitreous substitute. Further, hydrogel strongly inhibits the growth of bacteria E.coli and S.aureus. The drug loaded hydrogel showed sustained in-vitro drug release by the Fickian diffusion-mediated process (by Korsmeyer-Peppas and Peppas Sahlin model). Thus, the developed hydrogel may be used as a potential bacterial resistant AVS.

Gelatin/monetite electrospun scaffolds to regenerate bone tissue: Fabrication, characterization, and in-vitro evaluation.

This work is dedicated to combining nanotechnology with bone tissue engineering to prepare and characterize electrospun gelatin/monetite nanofibrous scaffold with improved physicochemical, mechanical, and biological properties. Nanofibrous scaffolds possessing fiber diameter in the range of 242-290 nm were prepared after incorporating varying content of monetite nanoparticles up to 7 wt % into the gelatin matrix using the electrospinning technique. Cross-linking of gelatin chains in the scaffold was performed using 0.25 wt% glutaraldehyde as indicated by imine (-CN-) bond formation in the FTIR analysis. With an increase in monetite addition up to 7 wt%, a decrease in swelling ratio and bio-degradability of cross-linked gelatin scaffolds was observed. Gelatin scaffold with 7 wt% monetite content registered the highest values of tensile strength and tensile modulus of 18.8 MPa and 170 MPa, as compared to 0% and 5 wt% monetite containing scaffolds respectively. Cell viability and differentiation were studied after culturing MG-63 cells onto the scaffolds from confocal microscopy of live and dead cells images, MTT assay, and alkaline phosphatase assay for a cell culture period of up to 21 days. It was observed that 7 wt % monetite containing gelatin scaffold exhibited better MG-63 cell adhesion, proliferation, higher biomineralization, and ALP activity compared to 0% and 5 wt% monetite containing electrospun scaffolds studied here.

Safety and Efficacy of Tranexamic Acid in Hip Hemiarthroplasty for Fracture Neck Femur: a Systematic Review and Meta-analysis.

Purpose: Although numerous systematic reviews and meta-analyses have established the efficacy of tranexamic acid (TXA) in hip fracture surgeries, the included studies in those reviews have included all types of surgical interventions ranging from fixation to arthroplasty. Hip hemiarthroplasty is usually indicated in the elderly patients with femoral neck fracture and these patients have associated severe comorbidities and cognitive impairment. These subsets of patients with femoral neck fracture needs appropriate perioperative care and judicious use of antifibrinolytics. There is no meta-analysis evaluating the safety and efficacy of intravenous TXA in these patients. Methods: Searches of PubMed, Embase and Cochrane Central Register of Controlled Trials databases revealed 102 studies on TXA in hip fracture surgeries. After screening, eight studies were found to be suitable for review. The primary objective of this meta-analysis was to compare blood transfusion rate between TXA vs. control in hip hemiarthroplasty. The secondary objectives were total blood loss, postoperative haemoglobin, surgical duration, length of hospital stay and side effects (VTE, readmission and 30 days mortality). Results: There were one RCT, one prospective cohort study and six retrospective studies. All studies recruited the elderly patients. Intravenous (IV) TXA administration resulted in significant reduction in requirement of blood transfusion (12.7% vs. 31.9%; OR 0.28; 95% CI 0.17-0.46; p < 00,001; I 2 = 73%). The TXA group had significantly decreased total blood loss (MD - 100.31; 95% CI - 153.79, - 46.83; p < 0.0002). The postoperative Hb in the TXA group was significantly higher than the control group (MD 0.53; 95% CI 0.35, 0.71; p < 0.00001). There was no significant difference in the incidences of VTE (0.97% vs. 0.73%, OR 1.27; p = 0.81; I 2 = 64%) and readmission rate (9.2% vs. 9.64%; OR 0.79; p = 0.54), but 30-d mortality rate was significantly lower in the TXA group (3.41% vs. 6.04%; OR 0.66; p = 0.03). Conclusions: Intravenous TXA is efficacious in the reduction of blood loss and transfusion need in hip hemiarthroplasty surgery for hip fracture, without increased risk of VTE. The blood conservation protocol led to decreased 30 days mortality in these fragile elderly patients. Level of evidence: III.

Correlation of bone mineral density using the dual energy x-ray absorptiometry and the magnetic resonance imaging of the lumbar spine in Indian patients.

Background: Dual-energy x-ray absorptiometry (DEXA) scan is extensively used to diagnose osteoporosis. But surprisingly, osteoporosis remains an underdiagnosed condition with many fragility fracture patients who have failed to undergo DEXA or received concomitant treatment for osteoporosis. Magnetic resonance imaging (MRI) of the lumbar spine is a routine radiological investigation bring done for low back pain. MRI can detect changes in the bone marrow signal intensity on the standard T1-weighted images. This correlation can be explored to measure osteoporosis in elderly and post-menopausal patients. The present study aims to find any correlation of bone mineral density using the DEXA and MRI of the lumbar spine in Indian patients. Methods: Five regions of interest (ROI) of size 130-180 mm2 were placed in the vertebral body in the mid-sagittal section and parasagittal sections on either side (four in L1-L4 and one outside body) of elderly patients who underwent MRI for back pain. They also underwent a DEXA scan for osteoporosis. Signal to Noise Ratio (SNR) was calculated by dividing the mean signal intensity obtained for each vertebra by the standard deviation of the noise. Similarly, SNR was measured for 24 controls. An MRI-based "M score" was calculated by getting the difference in SNR patients to SNR controls and then dividing it by the control's standard deviation (SD). Correlation between the T score on DEXA and M scores on MRI was found out. Results: With the M score greater than or equal to 2.82, the sensitivity was 87.5%, and the specificity was 76.5%. M scores negatively correlated with the T score. With the increase in the T score, the M score decreased. The Spearman correlation coefficient for the spine T score was -0.651, with a p-value of <0.001, and the hip T score was -0.428, with a p-value of 0.013. Conclusion: Our study indicates that MRI investigations are helpful in Osteoporosis assessments. Even though MRI may not replace DEXA, it can give insight into elderly patients who get an MRI routinely for back pain. It may also have a prognostic value.

A retrospective observational study of injury patterns associated with powered circular saw in subjects presenting to the emergency department of a tertiary care hospital.

Background: Powered circular saw-related injuries (PCSRIs) are responsible for a sizable proportion of occupational injuries presented to the emergency department (ED). The present study portrays the mechanisms, injury patterns, epidemiological parameters, and outcomes among subjects presenting with PCSRI to the ED. Methods: This retrospective observational study was conducted in the ED of a tertiary care hospital in eastern India. Clinical records of subjects with PCSRI from June 2019 to June 2022 were reviewed. Data pertaining to patients' demographic profiles and the patterns and mechanisms of injury were retrieved. The Modified Hand Injury Severity Score (MHISS) and the Injury Severity Score (ISS) were calculated. Statistical analysis was performed using R version 4.1.0. Results: A total of 175 subjects' data were analyzed. The median age was 34.5 years, and all subjects were men. The mean year of experience of the subjects was 6.2. The most common job category was carpentry (n = 63 [36%]), followed by "do it yourself work" (n = 26 [14.8%]). One hundred twenty-two (69.7%) subjects had hand injuries (HIs), and the left hand was involved in 85 (69.6%) subjects. The index finger was involved in 36 (29.5%) subjects, followed by the thumb (n = 31 [25.4%]). Laceration (n = 155 [88.5%]) was the most common injury pattern. The subjects' mean ISS and mean MHISS were 8.52 and 45, respectively. Conclusion: PCSRI is associated with moderate-to-severe HIs that are most common in occupational settings. Young male carpenters involved in wood and plywood work are more prone to injuries.

Dual cross-linked gellan gum/gelatin-based multifunctional nanocomposite hydrogel scaffold for full-thickness wound healing.

Biological macromolecules are excellent materials for wound dressing owing to their similar structure to the extracellular matrix and adjustable physicochemical properties. This research focuses on fabricating biological macromolecule-based hydrogel with desirable antibacterial, antioxidant, controlled drug release, cytocompatibility, and wound healing properties. Herein, different concentrations of nanoceria (NC) and flurbiprofen (FLU) drug-loaded gellan gum/gelatin (GG/Ge) based dual crosslinked (Ionic and EDC/NHS coupling) hydrogels were engineered. All fabricated hydrogels were hydrophilic, biodegradable, good strength, porous, antioxidant, hemocompatible and cytocompatible. Among all, hydrogel loaded with 500 µg/ml NC (GG/Ge/NC@FLU) exhibited desirable antioxidant, antibacterial (killed Staphylococcus aureus and Escherichia coli within 12 h), hemocompatible, cytocompatible, supports oxidative-stressed L929 cell growth and acted as a controlled release matrix for FLU, following Fickian diffusion, Peppas Sahlin and Korsmeyer-Peppas drug release models. Furthermore, nanocomposite hydrogel (GG/Ge/NC@FLU)-treated wounds of rats on day 14 demonstrated significantly higher collagen synthesis, nearly 100 % wound contractions, and efficiently decreased the expression of TNF-α and IL-1 while increasing the production of IL-10 and TNF-ß3, indicating antiinflammatory activity, and effectively reduced the expression of VEGF gene indicating effective angiogenesis than all other controls. In conclusion, the fabricated multifunctional GG/Ge/NC@FLU nanocomposite hydrogel shows promising potential for effectively treating full-thickness wound healing in a rat model.

Spontaneous Spinal Epidural Hematoma in a Near-term Pregnant Patient.

Introduction: Spontaneous development of spinal epidural hematoma (SEH) is rare condition with acute presentation and usually associated with some predisposing factors. Early diagnosis and management of SEH are very important because of the risk of permanent neurological deficit. Case Report: Here, we report a rare case of SEH in young pregnant female at 35 week of gestation who presented with short history of paraplegia that was diagnosed on magnetic resonance imaging (MRI) and treated successfully with delivery of the baby by caesarean section and release of cord compression by laminectomy. Conclusion: Spontaneous SEH can be rarely seen in pregnancy. MRI is the investigation of choice. Clinical suspicion is necessary for early management and better prognosis.

Development of decellularization protocol for caprine small intestine submucosa as a biomaterial.

Decellularized animal tissues have been proven to be promising biomaterials for various tissue engineering (TE) applications. Among various animal tissues, small intestine submucosa (SIS) has gained attention of many researchers due to its easy availability from the abattoir waste, excellent physicochemical and biological characteristics of a good biomaterial. In this study, Caprine SIS was decellularized to get decellularized caprine SIS (DG-SIS). For decellularization, several physical, chemical and enzymatic protocols have been described in the literature. To optimize the decellularization of caprine SIS, several decellularization protocol (DP), including an in-house developed by us, had been attempted, and effect of the different DPs on the obtained DG-SIS were assessed in terms of decellularization, physiochemical and biological properties. All the DPs differ in terms of decellularization, but three DPs where ionic detergent like sodium dodecyl sulphate (SDS) has been used, largely affect the native composition (e.g. glycosaminoglycans (GAGs)), biological properties and other physiochemical properties of the G-SIS as compared to the DP that uses hypertonic solution of potassium iodide (KI) and non-ionic detergent (TritonX-100). The obtained DG-SISs were fibrous, hemocompatible, biocompatible, hydrophilic, biodegradable and exhibited significant antibacterial activity. Therefore, the DG-SIS will be a prospective biomaterial for TE applications.

Chondroprotective effects of multiple PRP injections in osteoarthritis by apoptosis regulation and increased aggrecan synthesis- Immunohistochemistry based Guinea pig study.

OBJECTIVE: Use of Immunohistochemistry as a tool to assess anti-apoptotic effects and cartilage regeneration effects of PRP in guinea pig model of spontaneous OA. STUDY DESIGN: Controlled Laboratory Study involving Dunkin-Hartley guinea pigs. METHODS: 12 Dunkin-Hartley guinea pigs (weighing ∼600-800 g) were chosen for this study. One knee of each animal received 3 injections of allogenic PRP at weekly intervals (Group A = 12 Knees). The other knee received normal saline and acted as the control group (Group B = 12 Knees). Half of the animals from each group (subgroups A3 & B3 = 6 Knees each) were sacrificed at 3 months, and the remaining half (subgroups A6 & B6 = 6 Knees each) were sacrificed at 6 months after intervention. Immunohistochemistry (IHC) staining and evaluation were done for Collagen-II, Caspase-3 and Aggrecan. RESULTS: The mean IHC score for Caspase-3 were significantly low in PRP knees compared to placebo Knees at 3 months (P = 0.031) and 6 months (P = 0.012) suggesting its down-regulation and inhibition of apoptosis. The mean IHC score for content of collagen- II and aggrecan at 3 months were higher in PRP Knees (A3) compared to placebo (B3) (Not significant). At 6 months, the Mean IHC Score decreased in both PRP (A6) and Control Knees (B6) for Collagen, but increased for aggrecan compared to its value at 3 months; and this was better in PRP group than in the control (P = 0.024). CONCLUSION: Multiple injections of PRP has a chondroprotective role by its anti-apoptotic effect and by increasing the aggrecan content in ECM.

Dual-Plating in Distal Femur Fracture: A Systematic Review and Limited Meta-analysis.

INTRODUCTION: Although lateral locking plate has shown promising results in distal femur fracture, there are high rates of varus collapse and implant failure in comminuted metaphyseal and articular fractures. This systematic review evaluates the functional outcomes and complications of dual plating in the distal femur fracture. MATERIALS AND METHODS: Manual and electronic search of databases (PubMed, Medline Embase and Cochrane Central Register of Controlled Trials) was performed to retrieve studies on dual plate fixation in the distal femur fracture. Of the retrieved 925 articles, 12 were included after screening. RESULTS: There were one randomized-controlled, four prospective and seven retrospective studies. A total of 287 patients with 292 knees were evaluated (dual plating 213, single plating 76, lost to follow-up 3). The nonunion and delayed union rates following dual plate fixations were up to 12.5% and 33.3%, respectively. The mean healing time ranged from 11 weeks to 18 months. Good to excellent outcome was observed in 55-75% patients. There was no difference between the single plate and dual plate fixation with regards to the functional outcomes (VAS score, Neer Score and Kolmert's standard) and complications. Pooled analysis of the studies revealed a longer surgical duration (MD - 16.84, 95% CI - 25.34, - 8.35, p = 0.0001) and faster healing (MD 5.43, 95% CI 2.60, 8.26, p = 0.0002) in the double plate fixation group, but there was no difference in nonunion rate (9.2% vs. 0%, OR 4.95, p = 0.13) and blood loss (MD - 9.86, 95% CI - 44.97, 25.26, p = 0.58). CONCLUSION: Dual plating leads to a satisfactory union in the comminuted metaphyseal and articular fractures of the distal femur. There is no difference between the single plate and dual plate with regards to nonunion rate, blood loss, functional outcomes and complications. However, dual fixation leads to faster fracture healing at the cost of a longer surgical duration.