Prognostic Impact of Visceral Adipose Tissue Imaging Parameters in Patients with Cholangiocarcinoma after Surgical Resection.

Visceral adiposity is known to be related to poor prognosis in patients with cholangiocarcinoma; however, the prognostic significance of the qualitative features of adipose tissue in cholangiocarcinoma has yet to be well defined. This study investigated the prognostic impact of adipose tissue imaging parameters reflecting the quantity and qualitative characteristics of subcutaneous (SAT) and visceral (VAT) adipose tissue on recurrence-free survival (RFS) and overall survival (OS) in 94 patients undergoing resection of cholangiocarcinoma. The area, mean computed tomography (CT) attenuation, and mean 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake of SAT and VAT on positron emission tomography (PET)/CT for staging work-up were measured, and the relationship of these adipose tissue imaging parameters with clinicopathological factors and survival was assessed. TNM stage, histologic grade, lymphovascular invasion, and the size of cholangiocarcinoma showed positive correlations with adipose tissue imaging parameters. Multivariate survival analysis demonstrated that the visceral-to-subcutaneous adipose tissue area ratio (VSR) (p = 0.024; hazard ratio, 1.718) and mean FDG uptake of VAT (p = 0.033; hazard ratio, 9.781) were significant predictors for RFS, but all of the adipose tissue imaging parameters failed to show statistical significance for predicting OS. In addition to visceral adiposity, FDG uptake of VAT might be a promising prognostic parameter for predicting RFS in patients with cholangiocarcinoma.

Small-diameter vascular graft composing of core-shell structured micro-nanofibers loaded with heparin and VEGF for endothelialization and prevention of neointimal hyperplasia.

Despite the significant progress made in recent years, clinical issues with small-diameter vascular grafts related to low mechanical strength, thrombosis, intimal hyperplasia, and insufficient endothelialization remain unresolved. This study aims to design and fabricate a core-shell fibrous small-diameter vascular graft by co-axial electrospinning process, which will mechanically and biologically meet the benchmarks for blood vessel replacement. The presented graft (PGHV) comprised polycaprolactone/gelatin (shell) loaded with heparin-VEGF and polycaprolactone (core). This study hypothesized that the shell structure of the fibers would allow rapid degradation to release heparin-VEGF, and the core would provide mechanical strength for long-term application. Physico-mechanical evaluation, in vitro biocompatibility, and hemocompatibility assays were performed to ensure safe in vivo applications. After 25 days, the PGHV group released 79.47 ± 1.54% of heparin and 86.25 ± 1.19% of VEGF, and degradation of the shell was observed but the core remained pristine. Both the control (PG) and PGHV groups demonstrated robust mechanical properties. The PGHV group showed excellent biocompatibility and hemocompatibility compared to the PG group. After four months of rat aorta implantation, PGHV exhibited smooth muscle cell regeneration and complete endothelialization with a patency rate of 100%. The novel core-shell structured graft could be pivotal in vascular tissue regeneration application.

Multi-functional dual-layer nanofibrous membrane for prevention of postoperative pancreatic leakage.

Postoperative pancreatic leakage due to pancreatitis in patients is a life-threatening surgical complication. The majority of commercial barriers are unable to meet the demands for pancreatic leakage due to poor adhesiveness, toxicity, and inability to degrade. In this study, we fabricated mitomycin-c and thrombin-loaded multifunctional dual-layer nanofibrous membrane with a combination of alginate, PCL, and gelatin to resolve the leakage due to suture line disruption, promote hemostasis, wound healing, and prevent postoperative tissue adhesion. Electrospinning was used to fabricate the dual-layer system. The study results demonstrated that high gelatin and alginate content in the inner layer decreased the fiber diameter and water contact angle, and crosslinking allowed the membrane to be more hydrophilic, making it highly biodegradable, and adhering firmly to the tissue surfaces. The results of in vitro biocompatibility and hemostatic assay revealed that the dual-layer had a higher cell proliferation and showed effective hemostatic properties. Moreover, the in vivo studies and in silico molecular simulation indicated that the dual layer was covered at the wound site, prevented suture disruption and leakage, inhibited hemorrhage, and reduced postoperative tissue adhesion. Finally, the study results proved that dual-layer multifunctional nanofibrous membrane has a promising therapeutic potential in preventing postoperative pancreatic leakage.

An agarose-based TOCN-ECM bilayer lyophilized-hydrogel with hemostatic and regenerative properties for post-operative adhesion management.

This study used a unique approach by developing a bilayer system that can simultaneously accomplish non-adhesion, hemostatic, and tissue regenerative properties. In this system, agarose was used as a carrier material, with an agarose-TEMPO-oxidized cellulose nanofiber (TOCN), (AT) layer acting as a non-adhesion layer and an Agarose-Extracellular matrix, (AE) layer acting as a tissue regenerative layer. Thrombin was loaded on the AE layer as an initiator of the healing process, by hemostasis. AT 1:4 showed 79.3 % and AE 1:4 showed 84.66 % cell viability initially confirming the biocompatible nature of the layers. The AE layer showed cell attachment and proliferation on its surface whereas on the AT layer, cells are visible but no attachment was observed. Furthermore, in vivo analysis was conducted. The non-adhesive layer was grafted between the cecum and peritoneal wall which showed that (AT 1:4) displayed remarkable non-adhesion properties as compared to a commercial product and the non-treated group. Hemostasis and tissue regeneration ability were evaluated using rat liver models. The bleeding time of AE 1:4TH was recorded as 160 s and the blood loss was 5.6 g. The results showed that (AE 1:4) displayed effective regeneration ability in the liver model after two weeks.

Prognostic Significance of the Bone Marrow-to-Aorta Uptake Ratio on 2-Deoxy-2-[18F]fluoro-d-glucose Positron Emission Tomography/Computed Tomography in Patients with Cholangiocarcinoma.

2-Deoxy-2-[18F]fluoro-d-glucose (FDG) uptake of the reticuloendothelial system on positron emission tomography/computed tomography (PET/CT) is known to be related to systemic inflammatory response to cancer cells in patients with diverse malignancies. This retrospective study aimed to investigate whether FDG uptake by the reticuloendothelial system had a prognostic value in predicting progression-free survival (PFS) and overall survival (OS) in 138 cholangiocarcinoma patients. Quantifying FDG uptake of the aorta, bone marrow (BM), liver, and spleen from staging FDG PET/CT images, we found significant correlations between the BM-to-aorta uptake ratio (BAR), spleen-to-aorta uptake ratio, and BM-to-liver uptake ratio with tumor stage and serum inflammatory markers. In the multivariate survival analysis, BAR was an independent predictor of PFS (p = 0.016; hazard ratio, 2.308) and OS (p = 0.030; hazard ratio, 2.645). Patients with stages III-IV of the disease and a high BAR exhibited low 1-year PFS (35.8%) and OS (60.2%) rates, while those with stages I-II of the disease and low BAR showed robust rates of 90.0% and 96.7%, respectively. BAR measured on staging FDG PET/CT might be a potential imaging biomarker offering insights into the systemic inflammatory response and predicting prognosis in cholangiocarcinoma. This study highlights BAR as a promising, independent predictor with potential for personalized prognostication and treatment strategies.

In Vivo and In Vitro Investigation of a Novel Gelatin/Sodium Polyacrylate Composite Hemostatic Sponge for Topical Bleeding.

Designing a functional and efficient blood-clotting agent is a major challenge. In this research, hemostatic scaffolds (GSp) were prepared from the superabsorbent, inter-crosslinked polymer sodium polyacrylate (Sp) bound to a natural protein gelatin (G) loaded with thrombin (Th) by a cost-effective freeze-drying method. Five compositions were grafted (GSp0.0, Gsp0.1, GSp0.2, GSp0.3, GSp0.3-Th) where the concentration of Sp varied but the ratios of G remained the same. The fundamental physical characteristics that increased the amounts of Sp with G gave synergistic effects after interacting with thrombin. Due to the presence of superabsorbent polymer (SAP) swelling capacities in GSp0.3 and GSp0.3-Th surge forward 6265% and 6948%, respectively. Pore sizes became uniform and larger (ranging ≤ 300 µm) and well-interconnected. The water-contact angle declined in GSp0.3 and GSp0.3-Th to 75.73 ± 1.097 and 75.33 ± 0.8342 degrees, respectively, thus increasing hydrophilicity. The pH difference was found to be insignificant as well. In addition, an evaluation of the scaffold in in vitro biocompatibility with the L929 cell line showed cell viability >80%, so the samples were nontoxic and produced a favorable environment for cell proliferation. The composite GSp0.3-Th revealed the lowest HR (%) (2.601%), and the in vivo blood-clotting time (s) and blood loss (gm) supported hemostasis. Overall, the results showed that a novel GSp0.3-Th scaffold can be a potential candidate as a hemostatic agent.

Decellularized liver extracellular matrix and thrombin loaded biodegradable TOCN/Chitosan nanocomposite for hemostasis and wound healing in rat liver hemorrhage model.

During deep noncompressible wound management, surgery, transplantation or post-surgical hemorrhage, rapid blood absorption and hemostasis are the key factors to be taken into consideration to reduce unexpected deaths from severe trauma. In this study, a novel hemostatic biodegradable nanocomposite was fabricated where decellularized liver extracellular matrix (L-ECM) was loaded with two natural polymers (oxidized cellulose and chitosan) in association with thrombin. Plant-derived oxidized cellulose nanofiber (TOCN) and Chitosan (CS) from deacylated chitin were self-assembled with each other by electrostatic interactions. ECM was prepared by the whole tissue decellularization process and incorporated into the composite as a source of collagen and other integrated growth factors to promote wound healing. Thrombin was also anchored with the polymers by freeze drying for enhanced hemostatic efficiency of the composite. This study is the first of its kind to report non-solubilized L-ECM and thrombin loaded TOCN and CS composite, CN/CS/EM-Th for faster hemostasis effect in a rat tail amputation (~71 s) and liver avulsion model (~41 s). Furthermore, excellent liver wound regeneration efficacy was observed in-vivo in comparison to the commercially available oxidized regenerated cellulose product SURGICEL gauge.

Curative resection of leiomyosarcoma of the descending colon with metachronous liver metastasis: A case report.

BACKGROUND: Leiomyosarcoma (LMS) has a poor prognosis and rarely originates from the colon. If resection is possible, surgery is the first treatment most commonly considered. Unfortunately, no standard treatment exists for hepatic metastasis of LMS; although, several treatments, such as chemotherapy, radiotherapy, and surgery, have been used. Subsequently, the management of liver metastases remains controversial. CASE SUMMARY: We present a rare case of metachronous liver metastasis in a patient with LMS originating from the descending colon. A 38-year-old man initially reported abdominal pain and diarrhea over the previous two months. Colonoscopy revealed a 4-cm diameter mass in the descending colon, 40 cm from the anal verge. Computed tomography revealed intussusception of the descending colon due to the 4-cm mass. The patient underwent a left hemicolectomy. Immunohistochemical analysis of the tumor revealed that it was positive for smooth muscle actin and desmin, and negative for cluster of differentiation 34 (CD34), CD117, and discovered on gastrointestinal stromal tumor (GIST)-1, which are characteristic of gastrointestinal LMS. A single liver metastasis developed 11 mo post-operatively; the patient subsequently underwent curative resection thereof. The patient remained disease-free after six cycles of adjuvant chemotherapy (doxorubicin and ifosfamide), and 40 and 52 mo after liver resection and primary surgery, respectively. Similar cases were obtained from a search of Embase, PubMed, MEDLINE, and Google Scholar. CONCLUSION: Early diagnosis and surgical resection may be the only potential curative options for liver metastasis of gastrointestinal LMS.

Prognostic significance of programmed cell death-ligand 1 expression on immune cells and epithelial-mesenchymal transition expression in patients with hepatocellular carcinoma.

Purpose: Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers. However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumor-infiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role. Methods: Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis. Results: The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269-0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019-2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT- showed a significantly better prognosis than those who were TIL-/EMT+ (P = 0.049). Conclusion: This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti-PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.

In-vitro and in-vivo biocompatibility of dECM-alginate as a promising candidate in cell delivery for kidney regeneration.

In this study, kidney decellularized extracellular matrix (dECM) and alginate (ALG) hybrid injectable hydrogel, with the purpose of delivering progenitor cells for tissue engineering, were prepared by using a physical crosslinking method in a CaCl2 solution with high porosity for the exchange of nutrition and waste. In addition, the physical appearance and surface morphology of the hydrogel were investigated using optical and scanning electron microscopy, respectively. The functional groups of the dECM/ALG xerogels was examined via Fourier transform infrared spectroscopy. The biocompatibility of dECM/ALG xerogels was examined in-vitro using renal progenitor cells obtained from adult rat kidney. Enhanced biocompatibility and significant hemostatic behavior was noticed. Furthermore, the in-vivo biocompatibility of dECM/ALG hydrogel with progenitor cells was determined in the deep renal cortex for 7 and 21 days, in order to assess the foreign body reaction and inflammatory response. Early-stage glomerulus-like structure and dense linear cell network-like phenomenon were noticed. Loading of progenitor cells together with hydrogel enhances the cell density obviously due to cell migration from host and form a pattern. The desired early stage in-vivo response to progenitor cell-laden dECM/ALG hydrogel plays a potential role in kidney regeneration long term.

In-vitro and in-vivo hemostat evaluation of decellularized liver extra cellular matrix loaded chitosan/gelatin spongy scaffolds for liver injury.

Individually, Chitosan (C) and Gelatin (G) are increasingly being used for the simulation and testing of surgical procedures. In the present study, at combination of chitosan/gelatin (CG) was optimized and later enriched by the loading decellularized liver extracellular matrix powder (dLECM) prepared from porcine liver, we hypothesized CG-dLECM combination would enhance wound healing and reduce postoperative complications after liver surgery. Varying concentration of dLECM (1, 4, and 8 mg/ml) were loaded into CG, and evaluation was done to get the optimized composition. Preliminary analysis on the microstructure, in-vitro degradation, and blood clot kinetics and in-vitro cytocompatibility showed that the CG with 4 mg/ml dLECM (CG-E4) was the most suitable composition for further consideration. The prepared CG-E4 spongy scaffold enhances fast post-operative recovery with a higher blood absorption and fast clotting time (~50 s). In addition, CG-E4 spongy scaffold implanted at rat liver wound showed desired biocompatibility as evidenced by reduced wound size, earlier bioabsorption and accelerated liver regeneration. In the present study, we demonstrated that, CG with dLECM spongy scaffold as a potential hemostatic material in the prevention of excessive hemorrhage during surgeries.

Physico-mechanical and biological evaluation of an injectable m-TG cross-linked thrombin loaded amended gelatin hemostat to heal liver trauma.

Free flow hemostatic agents are dominating over non-flowable hemostats due to their ability to cover asymmetrical wound surfaces of any depth and easily remove excess materials with irrigation. The objective of this study was to evaluate the activation of a coagulation system both in vitro and in vivo. We assessed detailed physical characteristics of a microbial transglutaminase (m-TG) crosslinked thrombin (TB) laden Gelatin (Gel) hemostat sealant in vitro and its hemostatic efficacy for controlling bleeding caused by liver trauma in rats as well as its efficacy for organ regeneration after making a critical defect. The prepared hemostat gel showed almost seven times higher absorbance behavior than a negative control. Thrombogenicity of the prepared gel was determined based on platelet adhesion, whole blood clotting time, and total blood absorption behavior. In vivo blood absorption and hematological parameters were determined in an animal model after implantation. The prepared gel was able to lead to a fast post-operative recovery with a blood absorption at wound defect. High speed of homeostasis was achieved by a fast clotting time in about 1 min.

Polycaprolactone-gelatin membrane as a sealant biomaterial efficiently prevents postoperative anastomotic leakage with promoting tissue repair.

Anastomotic leakage due to post-surgical suture line disruption is one of the crucial factors affecting patient's survival and quality of life. To resolve the poor healing of surgical anastomosis and protect suture sites leakage, fibrous membrane sealing patch was developed using a synthetic polymer (polycaprolactone (PCL)) and biopolymer (gelatin). Electrospinning was used to develop fibrous architecture of membranes fabricated in different ratios (15% (w/v) PCL: 15% (w/v) gelatin mixing ratio of 1:1, 1:2, 1:3 and 1:4). Experimental findings suggested that, higher gelatin content in the membranes reduced the fiber diameter and contact angle, leading to a more hydrophilic scaffold facilitating attachment to the defect site. The degradation rate of various PCL-gelatin membranes (P1G1, P1G2, P1G3 and P1G4) was proportional to the gelatin content. Cytocompatibility was assessed using L929 cells while the P1G4 (PCL: gelatin 1:4 ratio) scaffold exhibited optimum outcome. From in vivo study, the wound site healed significantly without any leakage when the sutured area of rat caecum was covered with P1G4 membrane whereas rats in the control group (suture only) showed leakage after two weeks of surgery. In summary, the P1G4 membrane has potential to be applied as a post-surgical leakage-preventing tissue repair biomaterial.

Enlarged lymph nodes diagnosed with Langerhans cell histiocytosis found in a direct inguinal hernia: a case report.

It is unusual that an unexpected mass is encountered within a hernia sac. This report describes a patient diagnosed with Langerhans cell histiocytosis (LCH) after surgery for an inguinal hernia. A 64-year-old male patient presented with inguinal mass over a 1-year period. Direct inguinal hernias were found in both sides, and enlarged lymph nodes were found in both hernia sacs. Laparoscopic totally extraperitoneal repair was done, and one enlarged lymph node within inguinal hernia sac was excised for diagnostic purposes. Microscopic findings showed the distinctive cytologic features of Langerhans cells and immunohistochemical staining are positive for CD1a and S-100. LCH is a rare disorder, and the involvement of the lymph nodes with no other sites of disease is uncommon. To the best of our knowledge, this is the first report of LCH within an inguinal hernia sac. Multidisciplinary approach should be considered to provide better detection and treatment.

Spontaneous rupture of pyogenic liver abscess with subcapsular hemorrhage mimicking ruptured hepatocellular carcinoma: A case report.

RATIONALE: Spontaneous rupture of PLA (pyogenic liver abscess) is an extremely rare and life-threatening event. Ruptured PLA is very difficult to distinguish from malignant HCC (hepatocellular cancer) rupture or cholangiocarcinoma rupture on CT (computed tomography) scan. PATIENT CONCERNS: We describe the case of a 71-year-old man with fever, right upper abdominal pain, nausea with intermittent vomiting, and general fatigue. He had no medical or surgical history. DIAGNOSIS: CT scan showed a hypodense mass in right hepatic lobe and MRI (magnetic resonance imaging) revealed a heterogenous mass of ∼6 cm in segment VI of the liver and heterogenous fluid in the subcapsular region. We made a tentative diagnosis of HCC rupture with subcapsular hemorrhage based on these findings. INTERVENTION: After improving the patient's condition by administering empirical therapy consisting of intravenous antibiotics and fluids, we performed surgical exploration. Gross examination of the abdomen showed that almost the entire right hepatic lobe was hemorrhagic and affected by peritonitis. Therefore, we performed right hepatectomy. The intraoperative frozen biopsy revealed suspicious PLA with marked necrosis, neutrophil infiltration, and hemorrhagic rupture, although no malignant tissue or fungus was observed. The postoperative secondary pathology report confirmed the diagnosis of PLA with hemorrhagic rupture. OUTCOMES: The patient was discharged 13 days after the operation. Follow-up CT was performed 5 months after discharge and revealed no abnormal findings. LESSONS: A high index of suspicion is key to preventing misdiagnosis of ruptured PLA and improving prognosis. Furthermore, even if rupture of the PLA is initially localized, delayed peritonitis may occur during medical treatment. Therefore, vigilant monitoring is essential.

Synthesis and characterization of biphasic calcium phosphate laden thiolated hyaluronic acid hydrogel based scaffold: physical and in-vitro biocompatibility evaluations.

The present study focused on the combination of biphasic calcium phosphate (BCP) nanoparticles into the modified hyaluronic acid based injectable hydrogels for bone tissue engineering. Self-cross-linked thiolated hyaluronic acid (HA-HS) injectable hydrogels loaded with biphasic calcium phosphate (BCP) nanoparticles were prepared by disulfide cross-linking to mimic the extracellular matrix as a potential material for bone treatment. Varying concentration of HA-HS ranging between 1 and 5w/v% was tested to optimize the optimum concentration and were further modified with varying BCP concentrations for final optimization. Physico-chemical characterizations of the prepared hydrogel such as SEM, EDS, FT-IR, and XRD confirmed that the BCP has effectively loaded and distributed homogeneously in the HA-HS hydrogel. The results showed that the 3% (w/v) HA-HS hydrogel exhibits the appropriate properties for injectable hydrogel system such as gelation times, swelling rate and in vitro degradation behavior among all tested concentrations. Cell viability and cell proliferation using osteoblast cells (MC3T3-E1) demonstrated that the BCP laden modified hydrogel are biocompatible in vitro. In light of the encouraging results obtained, BCP laden HA-HS hydrogels might offer the potential to be used as injectable hydrogel in bone tissue engineering.

Laparoscopic drainage as a minimally invasive treatment for a psoas abscess: A single-center case series and literature review.

A psoas abscess is a rare but potentially devastating condition that is associated with risks of neurological deficits, septic shock, and even death. The current first-line treatment is percutaneous catheter drainage (PCD) under imaging guidance, combined with broad-spectrum antibiotics. Surgical drainage should be considered if PCD fails or is impossible.Although many studies on PCD and open surgical drainage have appeared, the outcomes of laparoscopic drainage have rarely been reported. Thus, we laparoscopically drained the psoas abscesses of 6 patients; drainage was complete and we encountered no recurrence or complication. All patients were evaluated by plain radiography, contrast-enhanced computed tomography, and laboratory tests; all were followed-up for 1 year. Laparoscopic drainage is a good treatment option when PCD fails, affording all the advantages of open surgery (complete drainage, resection of infected tissue, and contermporaneous treatment of concomitant lesions). Also, laparoscopic drainage is minimally invasive, requires a smaller incision, and allows rapid recovery.

Preoperative neutrophil-lymphocyte ratio and CEA is associated with poor prognosis in patients with synchronous colorectal cancer liver metastasis.

PURPOSE: Recently, the neutrophil-to-lymphocyte ratio (NLR), an inflammatory response marker, has been reported to be associated with the prognosis in patients with various type of cancer. However, there have been no studies until now that have explored the prognostic role of combined detection of NLR and CEA in patients with synchronous liver-limited colorectal metastases (sCRLM). METHODS: Eighty-three patients who histologically diagnosed as sCRLM were selected. Their laboratory and clinical data were collected retrospectively. Using receiver operating characteristic curve analysis, the cutoff value of NLR was calculated based on which patients were assigned to a high NLR (more than 1.94) group and low NLR (less than 1.94) group. A cutoff value of 100 ng/mL for serum CEA level was used in light of the previous literature. RESULTS: CEA level and Poorly differentiated histology of colon cancer was significantly correlated with high NLR (P = 0.005 and P = 0.048, respectively). The multivariate analysis identified the high NLR as independent prognostic factors for OS and DFS in all patients (P = 0.010 and P = 0.006, respectively). Patients with both low levels of NLR and CEA had a significantly longer OS and DFS (P = 0.026 and P = 0.009, respectively). CONCLUSION: In conclusion, elevated preoperative NLR is strongly correlated with both survival and recurrence in patients who have been diagnosed with resectable sCRLM. The combination of NLR and CEA level could be a more powerful prognostic marker than NLR alone.

Bone regeneration strategy by different sized multichanneled biphasic calcium phosphate granules: In vivo evaluation in rabbit model.

A variety of synthetic materials are currently in use as bone substitutes, among them a new calcium phosphate-based multichannel, cylindrical, granular bone substitute that is showing satisfactory biocompatibility and osteoconductivity in clinical applications. These cylindrical granules differ in their mechanical and morphological characteristics such as size, diameter, surface area, pore size, and porosity. The aim of this study is to investigate whether the sizes of these synthetic granules and the resultant inter-granular spaces formed by their filling critical-sized bone defects affect new bone formation characteristics and to determine the best formulations from these individual types by combining the granules in different proportions to optimize the bone tissue regeneration. We evaluated two types of multichanneled cylindrical granules, 1 mm and 3 mm in diameter, combined the granules in two different proportions (wt%), and compared their different mechanical, morphological, and in vitro and in vivo biocompatibility characteristics. We assessed in vitro biocompatibility and cytotoxicity using MC3T3-E1 osteoblast-like cells using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and confocal imaging. In vivo investigation in a rabbit model indicated that all four samples formed significantly better bone than the control after four weeks and eight weeks of implantation. Micro-computed tomography analysis showed more bone formation by the 1 mm cylindrical granules with 160 ± 10 µm channeled pore and 50% porosity than the other three samples ( p<.05), which we confirmed by histological analysis.

In vivo evaluation of injectable calcium phosphate cement composed of Zn- and Si-incorporated ß-tricalcium phosphate and monocalcium phosphate monohydrate for a critical sized defect of the rabbit femoral condyle.

Zinc (Zn) enhances bone formation with mineralization and is an essential element of osteoblastic proliferation. Silicon (Si) is important in apatite formation coupled with the promotion of osteogenesis. The primary focus of this work was the assessment of the bone healing capacity of calcium phosphate cements (CPC) composed of Zn- and Si-incorporated ß-tri calcium phosphate (TCP) and mono calcium phosphate mono hydrate (MCPM). Zn- and Si-incorporated ß-TCP was synthesized through a sol gel process with varying amounts of Zn: (3, 6, or 9% w/w) and 15% w/w Si. Fabricated CPC samples were characterized by scanning electron microscopy, setting time, injectability, compressive strength and initial pH change with time. Compositional analysis and the effects of Zn and Si on cellular interaction were evaluated by energy dispersive X-ray spectroscopy mapping, viability determination and F-actin assay. The data were used to optimize the CPC formulation. The efficacy of bone healing was investigated via implantation into critical sized rabbit femoral condyle defects for 4 and 8 weeks. CPC cement with 6% (w/w) Zn content was the best candidate for faster bone healing (bone to tibial volume ratio in 8 weeks: 22.78% ± 0.02). Significantly faster degradation was also revealed. Bone healing was significantly delayed when CPC cement with 9% (w/w) Zn was used. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 260-271, 2017.