Biliary reconstruction with a pedicled gallbladder flap in patients during pancreaticoduodenectomy.

BACKGROUND: Stricture formation at the biliary-enteric anastomosis can cause serious complications after pancreaticoduodenectomy while the anastomotic size is reported to significantly affect stricture formation. In this study, we aimed to determine the effect of a pedicled gallbladder flap used as an alternative to biliary reconstruction during pancreaticoduodenectomy in patients with a nondilated extrahepatic bile duct. METHODS: Data of patients with a nondilated extrahepatic bile duct, who underwent pancreaticoduodenectomy between October 2012 and July 2015 at the Department of Hepatobiliary and Pancreaticosplenic Surgery at Beijing Chaoyang Hospital, were collected. A pedicled gallbladder flap for biliary reconstruction was consecutively performed in patients with morphologically normal gallbladder, whereas patients with abnormal gallbladder morphology accept conventional biliary reconstruction. RESULTS: A total of 29 patients were enrolled in this study with 17 patients using a pedicled gallbladder flap and 12 patients using the conventional technique. Patients of the two groups had similar preoperative and operative parameters as well as similar early complication rates. No patients in the former group experienced biliary stricture or transient episodes of cholangitis over the follow-up period. While in the latter group, one patient had biliary stricture in the 14th month which was cured by intervene treatment. Another two patients had intermittently mild-to-moderate elevations in liver enzymes level from the 11th month and the 18th month, respectively, and were treated with medication. CONCLUSIONS: Biliary reconstruction with a pedicled gallbladder graft can be used as an alternative in patients with a nondilated extrahepatic bile duct during pancreaticoduodenectomy.

Isolated hepatic tuberculosis in the caudate lobe mimicking intrahepatic carcinoma.

Although tuberculosis (TB) remains a worldwide epidemic, isolated hepatic TB is an extremely rare entity and poorly described in the literature. Isolated hepatic TB may pose a diagnostic dilemma due to the non-specific clinical symptoms and imaging features. We present a case of a 54-year-old female with an isolated caseating granulomatous lesion at the caudate lobe of liver involving the pancreatic head.

Bilioenteric anastomotic stricture in patients with benign and malignant tumors: prevalence, risk factors and treatment.

BACKGROUND: Stricture formation at the bilioenteric anastomosis is a rare but important postoperative complication. However, information on this complication is lacking in the literature. In the present study, we aimed to assess its prevalence and predictive factors, and report our experience in managing bilioenteric anastomotic strictures over a ten-year period. METHODS: A total of 420 patients who had undergone bilioenteric anastomosis due to benign or malignant tumors between February 2001 and December 2011 were retrospectively reviewed. Univariate and multivariate modalities were used to identify predictive factors for anastomotic stricture occurrence. Furthermore, the treatment of anastomotic stricture was analyzed. RESULTS: Twenty-one patients (5.0%) were diagnosed with bilioenteric anastomotic stricture. There were 12 males and 9 females with a mean age of 61.6 years. The median time after operation to anastomotic stricture was 13.6 months (range, 1 month to 5 years). Multivariate analysis identified that surgeon volume (≤30 cases) (odds ratio: -1.860; P=0.044) was associated with the anastomotic stricture while bile duct size (>6 mm) (odds ratio: 2.871; P=0.0002) had a negative association. Balloon dilation was performed in 18 patients, biliary stenting in 6 patients, and reoperation in 4 patients. Five patients died of tumor recurrence, and one of heart disease. CONCLUSIONS: Bilioenteric anastomotic stricture is an uncommon complication that can be treated primarily by interventional procedures. Bilioenteric anastomosis may be performed by a surgeon in his earlier training period under the guidance of an experienced surgeon. Bile duct size >6 mm may play a protective role.

In vitro and in vivo enhancement of osteogenic capacity in a synthetic BMP-2 derived peptide-coated mineralized collagen composite.

Enhancement of osteogenic capacity was achieved in a mineralized collagen composite, nano-hydroxyapatite/collagen (nHAC), by loading with synthetic peptides derived from BMP-2 residues 32-48 (P17-BMP-2). Rabbit marrow stromal cells (MSCs) were used in vitro to study cell biocompatibility, attachment and differentiation on the mineralized collagen composite by a cell counting kit, scanning electron microscopy (SEM) and real-time reversed transcriptase-polymerase chain reaction analysis (RT-PCR). Optimal peptide dosage (1.0 µg/mL) was obtained by RT-PCR analysis in vitro. In addition, the relative expression level of OPN and OCN was significantly upregulated on P17-BMP-2/nHAC compared with nHAC. In vitro results of P17-BMP-2 release kinetics demonstrated that nHAC released P17-BMP-2 in a controlled and sustained manner. In the rabbit mandibular box-shaped bone defect model, osteogenic capacity of three groups (nHAC, P17-BMP-2/nHAC, rhBMP-2/nHAC) was evaluated. Compared to the nHAC group, bone repair responses in both P17-BMP-2/nHAC and rhBMP-2/nHAC group implants were significantly improved based on histological analysis. The osteogenic response of the P17-BMP-2/nHAC group was similar to that of the rhBMP-2/nHAC group.

Degradability of injectable calcium sulfate/mineralized collagen-based bone repair material and its effect on bone tissue regeneration.

The nHAC/CSH composite is an injectable bone repair material with controllable injectability and self-setting properties prepared by introducing calcium sulfate hemihydrate (CSH) into mineralized collagen (nHAC). When mixed with water, the nHAC/CSH composites can be transformed into mineralized collagen/calcium sulfate dihydrate (nHAC/CSD) composites. The nHAC/CSD composites have good biocompatibility and osteogenic capability. Considering that the degradation behavior of bone repair material is another important factor for its clinical applications, the degradability of nHAC/CSD composites was studied. The results showed that the degradation ratio of the nHAC/CSD composites with lower nHAC content increased with the L/S ratio increase of injectable materials, but the variety of L/S ratio had no significant effect on the degradation ratio of the nHAC/CSD composites with higher nHAC content. Increasing nHAC content in the composites could slow down the degradation of nHAC/CSD composite. Setting accelerator had no significant effect on the degradability of nHAC/CSD composites. In vivo histological analysis suggests that the degradation rate of materials can match the growth rate of new mandibular bone tissues in the implanted site of rabbit. The regulable degradability of materials resulting from the special prescriptions of injectable nHAC/CSH composites will further improve the workability of nHAC/CSD composites.

Improved workability of injectable calcium sulfate bone cement by regulation of self-setting properties.

Calcium sulfate hemihydrate (CSH) powder as an injectable bone cement was prepared by hydrothermal synthesis of calcium sulfate dihydrate (CSD). The prepared materials showed X-ray diffraction peaks corresponding to the CSH structure without any secondary phases, implying complete conversion from CSD phase to CSH phase. Thermogravimetric (TG) analyses showed the crystal water content of CSH was about 6.0% (wt.), which is near to the theoretic crystal water value of CSH. From scanning electron microscopy (SEM) micrographs, sheet crystal structure of CSD was observed to transform into rod-like crystal structure of CSH. Most interesting and important of all, CSD as setting accelerator was also introduced into CSH powder to regulate self-setting properties of injectable CSH paste, and thus the self-setting time of CSH paste can be regulated from near 30 min to less than 5 min by adding various amounts of setting accelerator. Because CSD is not only the reactant of preparing CSH but also the final solidified product of CSH, the setting accelerator has no significant effect on the other properties of materials, such as mechanical properties. In vitro biocompatibility and in vivo histology studies have demonstrated that the materials have good biocompatibility and good efficacy in bone regeneration. All these will further improve the workability of CSH in clinic applications.

Osteogenesis of mineralized collagen bone graft modified by PLA and calcium sulfate hemihydrate: in vivo study.

In this study, the biocompatibility and bone regeneration performance of nano-hydroxyapatite/collagen/poly(L-lactide) (nHAC/PLA) and nano-hydroxyapatite/collagen/calcium sulfate hemihydrate (nHAC/CSH) as bone-filling materials were evaluated and compared in a critical box-shaped defect model in the mandible of the rabbits. In vivo results indicated that there was significant difference in early bone remodeling between two types of bone substitutes. nHAC/PLA has shown excellent biocompatibility, but no adequate handling properties. The addition of CSH to nHAC provided better manipulability compared to nHAC/PLA. Furthermore, nHAC/CSH possesses superior properties in restoring critical-sized bone defects of maxillofacial region at the early stage of remodeling over nHAC/PLA. Our results suggested that nHAC/CSH could be an alternative to the conventionally used bone tissue engineering materials.

Adipose stem cells controlled by surface chemistry.

This study investigated how human adipose stem cells (hASCs) could be influenced by surface chemistry. Self-assembled monolayers of alkanethiolates on gold were introduced as a surface chemistry model to provide a range of functional groups such as OH, COOH, NH2, Phenyl, SH, Br, and CH3 on surfaces. Initially, morphological changes of hASCs in response to different surface chemistries were observed with focal adhesion. Cell growth behaviour evaluated by Cell Counting Kit-8 (CCK8) assay (Dojindo Molecular Technologies Inc., Shanghai, China) and cytoskeletal F-actin Biochem Kit™ (Denver, CO, USA) staining revealed a descending order of growth rate on the following surfaces: NH2 > SH > COOH > Phenyl > Br > OH > CH3. The mRNA expressions of lineage specific markers including alkaline phosphatase (ALP), osteocalcin (OCN), type II collagen, aggrecan, peroxisome proliferator-activated receptor gamma (PPARγ), and fatty acid binding protein-2 (aP2), were determined using real-time reversed transcriptase-polymerase chain reaction (RT-PCR). Results revealed that NH2 favoured hASC differentiation toward osteogenic, while phenyl and SH promoted chondrogenic differentiation of hASCs with a high level up-regulation of type II collagen and aggrecan. hASCs on Br increased in PPARγ and aP2 expression, indicating adipogenic differentiation. These results highlight the vital role of surface chemistry on the modulation of hASC differentiation and suggests chemical methods for designing biomaterials for stem cell-based tissue regeneration.

Repair of calvarial defects in rabbits with platelet-rich plasma as the scaffold for carrying bone marrow stromal cells.

OBJECTIVE: Platelet-rich plasma (PRP) is becoming a new application in tissue engineering and a developing area for clinicians and researchers because it is a natural source of growth factors, many of which can accelerate and promote bone regeneration. However, few studies have reported the potentiality of using PRP as a scaffold in bone tissue engineering. The present study investigated the feasibility of using PRP as a scaffold to carry bone marrow stromal cells (BMSCs) to repair calvarial defects in a rabbit model. STUDY DESIGN: The primary cultured BMSCs were divided into 2 groups. One group was induced with dexamethasone and the other was not induced. Full-thickness bone defects of 5-mm diameter (4 defects per calvarium) were created on the calvaria of 10 New Zealand white rabbits. PRP or whole blood was used, respectively to incorporate the induced or uninduced BMSCs. Then, the composites were activated and applied to repair the defects. The samples were harvested 8 weeks later and bone regeneration was assessed grossly and analyzed by radiographic or histologic examination. RESULTS: Eight weeks after the implantation of the materials, substantial bone regeneration was observed at the calvarial defect restored with PRP incorporating the induced BMSCs. Less new bone formation was observed at the defect implanted with PRP incorporating the uninduced BMSCs. In contrast, no bone regeneration was detected at the defects implanted with the whole blood incorporating BMSCs, whether the BMSCs were induced or not. CONCLUSIONS: PRP can be used as a scaffold to carry in vitro expanded BMSCs to repair a rabbit's calvarial defect, but its inductive ability to BMSCs was limited.

Mechanical properties and in vitro bioactivity of injectable and self-setting calcium sulfate/nano-HA/collagen bone graft substitute.

Calcium sulfate hemihydrate (CSH) was introduced into the mineralized collagen (nHAC) to prepare an injectable and self-setting in situ bone graft substitute. The mechanical properties of materials, which are dependant on the L/S ratio, the content of nHAC and setting accelerator, were discussed based on the satisfying injectability and setting properties. It was found that the compressive strength and modulus of materials increased with the decrease of nHAC content and L/S ratio. CSD as setting accelerator hardly had an effect on the compressive properties of materials because it is not only the reactant of preparing CSH but also the final solidified product of CSH instead of a foreign body. Though the compressive properties of nHAC/CSD composites changed with the variety of nHAC content and L/S ratio, the compressive strength and modulus of the materials ranged from 2.0 to nearly 20.0 MPa and 100.0 to 800.0 MPa, respectively, which are similar to that of cancellous bone. In vitro cell behavior demonstrated that the composites could provide adequate environment for cell adhesion and proliferation. All these indicated that the nHAC/CSH composites were a potential scaffold for bone tissue engineering.

Injectable calcium sulfate/mineralized collagen-based bone repair materials with regulable self-setting properties.

An injectable and self-setting bone repair materials (nano-hydroxyapatite/collagen/calcium sulfate hemihydrate, nHAC/CSH) was developed in this study. The nano-hydroxyapatite/collagen (nHAC) composite, which is the mineralized fibril by self-assembly of nano-hydrocyapatite and collagen, has the same features as natural bone in both main hierarchical microstructure and composition. It is a bioactive osteoconductor due to its high level of biocompatibility and appropriate degradation rate. However, this material lacks handling characteristics because of its particle or solid-preformed block shape. Herein, calcium sulfate hemihydrate (CSH) was introduced into nHAC to prepare an injectable and self-setting in situ bone repair materials. The morphology of materials was observed using SEM. Most important and interesting of all, calcium sulfate dihydrate (CSD), which is not only the reactant of preparing CSH but also the final solidified product of CSH, was introduced into nHAC as setting accelerator to regulate self-setting properties of injectable nHAC/CSH composite, and thus the self-setting time of nHAC/CSH composite can be regulated from more than 100 min to about 30 min and even less than 20 min by adding various amount of setting accelerator. The compressive properties of bone graft substitute after final setting are similar to those of cancellous bone. CSD as an excellent setting accelerator has no significant effect on the mechanical property and degradability of bone repair materials. In vitro biocompatibility and in vivo histology studies demonstrated that the nHAC/CSH composite could provide more adequate stimulus for cell adhesion and proliferation, embodying favorable cell biocompatibility and a strong ability to accelerate bone formation. It can offer a satisfactory biological environment for growing new bone in the implants and for stimulating bone formation.

Structure and biocompatibility of an injectable bone regeneration composite.

With the development of minimally invasive techniques, injectable materials have become one of the major hotspots in the biomaterial field. We have developed an injectable bone regeneration composite (IBRC) using calcium alginate hydrogel as matrix to carry nano-hydroxyapatite/collagen particles. In this work, we evaluated the homogeneity of IBRC by dry/wet weight ratio test. The results showed that the structural homogeneity was determined by controlling the molar ratios of trisodium phosphate to calcium sulfate rather than alginate concentration in the studied ranges. Pore sizes of wet IBRC samples were characterized by thermoporometry. The pore properties of dried IBRC were tested by mercury porosimetry. Average pore size and porosity of dried IBRC declined with increasing alginate concentration. In contrast, surprisingly, pore size of wet homogeneous IBRC increased with increasing alginate concentration. Meanwhile, the swelling ratio did not increase with varying alginate concentration, but the swelling degree increased with increasing alginate concentration. In vitro cell culture showed that IBRC had no obvious cytotoxic effect on the rat bone mesenchymal stem cells. The morphology and viability of cells were also related to MR value. IBRC had good histocompatibility with a mild short-term inflammatory response in rat dorsum muscle. In addition, the excellent ability of IBRC to promote bone healing was confirmed by 5-mm-diameter cranial defects using histological analysis and bone mineral density measurement.

Injectable bone cement based on mineralized collagen.

A novel injectable bone cement based on mineralized collagen was reported in this paper. The cement was fabricated by introducing calcium sulfate hemihydrate (CaSO(4).1/2H(2)O, CSH) into nano-hydroxyapatite/collagen (nHAC). The workability, in vitro degradation, in vitro and in vivo biocompatibility of the cement (nHAC/CSH) were studied. The comparative tests via in vitro and in vivo showed that the nHAC/CSH composite cement processed better biocompatibiltiy than that of pure CSH cement. The results implied that this new injectable cement should be very promising for bone repair.

Improvement on the performance of bone regeneration of calcium sulfate hemihydrate by adding mineralized collagen.

Comparative investigations of bone regeneration performance for calcium sulfate hemihydrate (CaSO(4).(1/2)H(2)O; CSH) only and CSH with mineralized collagen are reported in this article. The mineralized collagen is the nanohydroxyapatite/collagen (nHAC). The investigations included biocompatibility in vitro and performance of bone repair in vivo. Quantitative and qualitative biocompatibility assays with bone stromal stem cells were performed. A critical box-shaped defect model in the mandible of the rabbit was used to evaluate the bone-remodeling ability of CSH and nHAC/CSH. Results in vitro indicated that the nHAC/CSH significantly improved bioactivity compared with that of CSH, especially in promoting cell adhesion. Further, a higher bone remodeling activity was observed around nHAC/CSH composite than the CSH, especially at the early stage of remodeling. This result means that nHAC/CSH could cause an earlier accelerator and better osseointegration for bone repair than CSH only.