Ibuprofen-loaded bilayer electrospun mesh modulates host response toward promoting full-thickness abdominal wall defect repair.

Pro-inflammatory response impairs the constructive repair of abdominal wall defects after mesh implantation. Electrospinning-aid functionalization has the potential to improve the highly orchestrated response by attenuating the over-activation of foreign body reactions. Herein, we combined poly(L-lactic acid-co-caprolactone) (PLLA-CL) with gelatin proportionally via electrospinning, with Ibuprofen (IBU) incorporation to fabricate a bilayer mesh for the repair improvement. The PLLA-CL/gelatin/IBU (PGI) mesh was characterized in vitro and implanted into the rat model with a full-thickness defect for a comprehensive evaluation in comparison to the PLLA-CL/gelatin (PG) and off-the-shelf small intestinal submucosa (SIS) meshes. The bilayer PGI mesh presented a sustained release of IBU over 21 days with degradation in vitro and developed less-intensive intraperitoneal adhesion along with a histologically weaker inflammatory response than the PG mesh after 28 days. It elicited an M2 macrophage-dominant foreign body reaction within the process, leading to a pro-remodeling response similar to the biological SIS mesh, which was superior to the PG mesh. The PGI mesh provided preponderant mechanical supports over the SIS mesh and the native abdominal wall with similar compliance. Collectively, the newly developed mesh advances the intraperitoneal applicability of electrospun meshes by guiding a pro-remodeling response and offers a feasible functionalization approach upon immunomodulation.

Development of a Silk Fibroin-Small Intestinal Submucosa Small-Diameter Vascular Graft with Sequential VEGF and TGF-ß1 Inhibitor Delivery for In Situ Tissue Engineering.

Proper endothelialization and limited collagen deposition on the luminal surface after graft implantation plays a crucial role to prevent the occurrence of stenosis. To achieve these conditions, a biodegradable graft with adequate mechanical properties and the ability to sequentially deliver therapeutic agents isfabricated. In this study, a dual-release system is constructed through coaxial electrospinning by incorporating recombinant human vascular endothelial growth factor (VEGF) and transforming growth factor ß1 (TGF-ß1) inhibitor into silk fibroin (SF) nanofibers to form a bioactive membrane. The functionalized SF membrane as the inner layer of the graft is characterized by the release profile, cell proliferation and protein expression. It presents excellent biocompatibility and biodegradation, facilitating cell attachment, proliferation, and infiltration. The core-shell structure enables rapid VEGF release within 10 days and sustained plasmid delivery for 21 days. A 2.0-mm-diameter vascular graft is fabricated by integrating the SF membrane with decellularized porcine small intestinal submucosa (SIS), aiming to facilitate the integration process under a stable extracellular matrix structure. The bioengineered graft is functionalized with the sequential administration of VEGF and TGF-ß1, and with the reinforced and compatible mechanical properties, thereby offers an orchestrated solution for stenosis with potential for in situ vascular tissue engineering applications.

Comparison of open and laparoscopic inguinal-hernia repair in octogenarians.

INTRODUCTION: Although the advantages of laparoscopic inguinal hernia repair in the general population have been reported, its role in octogenarians has yet to be elucidated. This retrospective study was designed to compare the outcomes of open and laparoscopic inguinal hernia repairs in octogenarians. MATERIALS AND METHODS: The data of octogenarians who underwent laparoscopic (n = 81) or open (n = 121) inguinal hernia repair were collected from January 2017 to December 2019. Statistical analysis variables included basic epidemiological data of patients, surgical procedures, comorbidities, postoperative pain, complications, recurrence, and other data. RESULTS: There were no significant differences between the two groups in terms of sex, body mass index, recurrent hernias, comorbidities, postoperative complications, and recurrence. The American Society of Anesthesiologists (ASA) class and the proportion of scrotal hernias in the open group were higher than those of the laparoscopic group, whereas the proportion of bilateral hernias in the laparoscopic group was higher than that in the open group. The postoperative pain scores of the laparoscopic group were lower than those of the open group. CONCLUSIONS: In octogenarians, both laparoscopic and open inguinal hernia repairs are safe and feasible, but an appropriate surgical plan is crucial for obtaining better treatment effect.

Development of a decellularized human amniotic membrane-based electrospun vascular graft capable of rapid remodeling for small-diameter vascular applications.

The performance of small-diameter vascular grafts adapted to vascular replacement is commonly hindered by stenosis. To address this issue, a graft featuring rapid remodeling with degradation is warranted. In this work, a 1.8-mm-diameter graft was constructed by fabricating a decellularized human amniotic membrane (HAM) with polycaprolactone (PCL)/silk fibroin (SF) around it through electrospinning, namely, an HPS graft, and applied in a rat aortic grafting model for comparison to a decellularized porcine small intestinal submucosa (SIS)-integrated PCL/SF (SPS) graft and an autologous aorta. In vitro studies demonstrated that HAM provided a bioactive milieu for rapid endothelial cell proliferation and resisting fibroblast-induced collagen secretion. PCL/SF provides a biocompatible microenvironment for cellular infiltration with mechanical properties resembling those of the rat aorta. In vivo studies showed that the HPS graft induced functional endothelialization more rapidly, along with less intensive ECM deposition than the SPS graft upon the histologically weaker inflammatory response and foreign body reaction 4 weeks after implantation, and maintained patency by progressively stabilizing the remodeling structure approximating the native counterparts over 24 weeks. The bioengineered graft expands the applicability of allogeneic matrices with degradable electrospun polymers for long-term in situ vascular applications. STATEMENT OF SIGNIFICANCE: An orchestrated remodeling of the vascular graft, featuring rapid endothelialization and resisting extracellular matrix (ECM) deposition on the luminal surface, with a mechanically stable structure, is requisite for long-term vascular patency. Nevertheless, off-the-shelf grafts might not fulfil the criteria under abdominal aortic pressure. Herein, we fabricated a 1.8-mm-diameter vascular graft through the integration of a decellularized human amniotic membrane (HAM) with electrospun polycaprolactone (PCL)/silk fibroin (SF). In a rat aortic grafting model, the graft is capable of rapid endothelialization and resisting collagen deposition and provides a native-like mechanical structure for stabilizing the remodeling process towards that of the native aorta. This bioengineered graft has potential for small-diameter vascular regeneration, and provides advanced strategies to facilitate full-remodeling tissue applications.

Incorporation of magnesium oxide nanoparticles into electrospun membranes improves pro-angiogenic activity and promotes diabetic wound healing.

Deficient angiogenesis is the major abnormality impairing the healing process of diabetic wounds. Electrospun nanofiber membranes have shown promise for wound dressing. A prerequisite for electrospun membranes to treating diabetic wounds is the capacity to promote angiogenesis of wounds. Current approaches are mainly focused on the use of pro-angiogenic growth factors to enhance the angiogenic properties of electrospun membranes. Despite improved angiogenesis, both the incorporation of growth factors into electrospun nanofibers and maintenance of its activity in the long term is of technical difficulty. We herein report an electrospun membrane made of polycaprolactone (PCL)/gelatin/magnesium oxide (MgO) nanoparticles (PCL/gelatin/MgO), which releases magnesium ions (Mg2+) to enhance angiogenesis. MgO-incorporated membranes promote the proliferation of human umbilical vein endothelial cells and upregulate vascular endothelial growth factor (VEGF) production in vitro. Subcutaneous implantation study in a rat model demonstrates that the MgO-incorporated membrane shows a faster degradation profile and elicits moderate immune responses that gradually resolve. Upon subcutaneous implantation, PCL/gelatin/MgO membranes allow robust blood vessel formation as early as one week after surgery, and the newly formed capillary networks enrich within the degrading membrane over time. PCL/gelatin/MgO membranes significantly accelerated diabetic wound healing by suppressing inflammatory responses, promoting angiogenesis, and boosting granulation formation. Taken together, these results are implicative to rationally designing magnesium-incorporated electrospun membranes with improved pro-angiogenic activity for treating diabetic wounds.

A study of the "Swiss-roll" folding method for placement of self-gripping mesh in TAPP.

BACKGROUND: Using self-gripping mesh eliminates the need for additional mechanical fixation in laparoscopic groin hernia repair when surgeons plan to fix it. However, the mesh's 'self-gripping' characteristic makes it much more difficult to unfold and place. Here, the novel "Swiss-roll" placement method of folding self-gripping mesh is introduced and compared to the common folding placement method. MATERIAL AND METHODS: The cohort of this prospective randomized controlled study included 100 patients who underwent transabdominal preperitoneal (TAPP) groin hernia repair in the Department of Hernia and Abdominal Wall Surgery of Shanghai East Hospital between January and December 2018. The patients were randomly assigned to the "Swiss-roll" folding group or the common folding group. The time required for mesh placement, total surgical duration, and the incidences of postoperative pain and complications were compared. RESULTS: The times required for mesh placement in the "Swiss-roll" and common folding groups were 155.10 ± 48.66 and 202.80 ± 61.05 sec, respectively. The "Swiss-roll" folding method significantly shortened the time required for mesh placement (p = 0.000). There were no significant differences in total surgical duration and the incidences of postoperative pain and complications between the two groups. CONCLUSIONS: The "Swiss-roll" folding method facilitates self-gripping mesh placement without increasing the incidence of complications and recurrences in TAPP.

Nanofiber configuration affects biological performance of decellularized meniscus extracellular matrix incorporated electrospun scaffolds.

Electrospinning represents the simplest approach to fabricate nanofiber scaffolds that approximate the heterogeneous fibrous structure of the meniscus. More effort is needed to understand the relationship between scaffold properties and cell responses to determine the appropriate scaffolds supporting meniscus tissue repair and regeneration. In this study, we investigate the influence of nanofiber configuration of electrospun scaffolds on phenotype and matrix production of meniscus cells, as well as on scaffold degradation behaviors and biocompatibility. Twisting electrospun nanofibers into yarns not only recapitulates the major collagen bundles of the meniscus but also increases the pore size and porosity of resultant scaffolds. The yarn scaffold significantly regulated expression levels of meniscus-associated genes and promoted extracellular matrix production compared with conventional electrospun scaffolds with random or aligned nanofiber orientation. Additionally, the yarn scaffold allowed considerable cell infiltration and experienced faster degradation and tissue remodeling upon subcutaneous implantation in a rat model. These results suggest that nanofiber configuration dictates cell interactions, scaffold degradation and integration with host tissue, providing design parameters of porosity and pore size of electrospun scaffolds toward meniscus repair.

The evaluation of functional small intestinal submucosa for abdominal wall defect repair in a rat model: Potent effect of sequential release of VEGF and TGF-ß1 on host integration.

Ineffective vessel penetration and extracellular matrix (ECM) remodeling are responsible for the failure of porcine small intestinal submucosa (SIS)-repaired abdominal wall defects. Combined growth factors could be used as directing signals in a nature-mimicking strategy to improve this repair through mesh functionalization. In this work, vascular endothelial growth factor (VEGF) and transforming growth factor ß1 (TGF-ß1) were incorporated into a silk fibroin membrane via coaxial aqueous electrospinning to exploit their benefits of biological interactions. The membrane was sandwiched into the SIS bilayer as a functional mesh to repair partial-thickness defects in a rat model. Membrane characterization demonstrated that the core-shell structure ensured the independent distribution and sequential release of two regulators and protection of their bioactivities, which were confirmed by cell viability and protein expression. The mesh was further assessed to facilitate vasculature formation and collagen secretion in vitro, and exhibited better host integration than VEGF- or TGF-ß1-containing mesh and developed reinforced mechanical properties compared with the VEGF-containing mesh after 28 days in vivo. Determination of the underlying biological interactions revealed that rapid VEGF release promotes angiogenesis and collagen secretion but initially potentiates the inflammatory response. Sustained TGF-ß1 release at relatively low concentrations promoted VEGF for vessel permeation and maturation and steadily induced ECM remodeling under milder foreign body reactions. The functionalization of SIS improves repair by sufficient integration with timely remodeling and helps elucidate the related regulatory interactions.

Tailoring electrospun mesh for a compliant remodeling in the repair of full-thickness abdominal wall defect - The role of decellularized human amniotic membrane and silk fibroin.

Tailored electrospun meshes have been increasingly explored for abdominal wall defect repair in preclinical and clinical studies. However, the fabrication of a bioengineered mesh adapts to the intraperitoneal repair for a compliant remodeling remains a great challenge. In this study, we fabricated a functional mesh by combining polycaprolactone (PCL) with silk fibroin (SF) and decellularized human amniotic membrane (HAM) proportionally via electrospinning. SF was integrated with PCL (40:60 w/w) to regulate the structural flexibility. Micronized HAM was incorporated to PCL/SF (10:90 w/w) to provide a biocompatible milieu with functions being conferred to facilitate intraperitoneal repair. After the blend electrospinning, the PCL/SF/HAM mesh was characterized in vitro and implanted into the rat model with a full-thickness defect for a comprehensive evaluation in comparison to the PCL and PCL/SF meshes. The results demonstrated that electrospinning fabricated PCL stabilized the mechanical elongation toward approximating the native counterparts after integrating with SF. After integrating with HAM, which is coupled with diverse biomolecular compositions, the developed PCL/SF/HAM mesh provided a better microenvironment for cell proliferation and vasculogenic network over other meshes without HAM addition and possessed the functions capable of inhibiting transforming growth factor ß1 (TGF-ß1) expression and collagen secretion under inflammatory conditions. Moreover, the functional mesh developed less-intensive adhesion along with histologically weaker inflammatory response and foreign body reaction than the PCL and PCL/SF meshes after 90 days in vivo. During the remodeling process, the bioactive structure induced more pronounced neovascularization and remarkable incorporation of collagen and elastin fibers and contractile filaments for a mechanically sufficient and physiologically stiffness-matched healing. This tailor-made mesh expands the intraperitoneal applicability of conventional electrospun meshes for a compliant remodeling in the repair of abdominal wall defects.

Functionalized Strategies and Mechanisms of the Emerging Mesh for Abdominal Wall Repair and Regeneration.

Meshes have been the overwhelmingly popular choice for the repair of abdominal wall defects to retrieve the bodily integrity of musculofascial layer. Broadly, they are classified into synthetic, biological and composite mesh based on their mechanical and biocompatible features. With the development of anatomical repair techniques and the increasing requirements of constructive remodeling, however, none of these options satisfactorily manages the conditional repair. In both preclinical and clinical studies, materials/agents equipped with distinct functions have been characterized and applied to improve mesh-aided repair, with the importance of mesh functionalization being highlighted. However, limited information exists on systemic comparisons of the underlying mechanisms with respect to functionalized strategies, which are fundamental throughout repair and regeneration. Herein, we address this topic and summarize the current literature by subdividing common functions of the mesh into biomechanics-matched, macrophage-mediated, integration-enhanced, anti-infective and antiadhesive characteristics for a comprehensive overview. In particular, we elaborate their effects separately with respect to host response and integration and discuss their respective advances, challenges and future directions toward a clinical alternative. From the vastly different approaches, we provide insight into the mechanisms involved and offer suggestions for personalized modifications of these emerging meshes.

Magnesium oxide-incorporated electrospun membranes inhibit bacterial infections and promote the healing process of infected wounds.

Bacterial infections cause severe secondary damage to wounds and hinder wound healing processes. We prepared magnesium oxide (MgO) nanoparticle-incorporated nanofibrous membranes by electrospinning and investigated their potential for wound dressing and fighting bacterial infection. MgO-Incorporated membranes possessed good elasticity and flexibility similar to native skin tissue and were hydrophilic, ensuring comfortable contact with wound beds. The cytocompatibility of membranes was dependent on the amounts of incorporated MgO nanoparticles: lower amounts promoted while higher amounts suppressed the proliferation of fibroblasts, endothelial cells, and macrophages. The antibacterial capacity of membranes was proportional to the amounts of incorporated MgO nanoparticles and they inhibited more than 98% E. coli, 90% S. aureus, and 94% S. epidermidis. MgO nanoparticle-incorporated membranes effectively suppressed bacterial infection and significantly promoted the healing processes of infected full-thickness wounds in a rat model. Subcutaneous implantation demonstrated that the incorporation of MgO nanoparticles into electrospun membranes elevated their bioactivity as evidenced by considerable cell infiltration into their dense nanofiber configuration and enhanced the remodeling of implanted membranes. This study highlights the potential of MgO-incorporated electrospun membranes in preventing bacterial infections of wounds.

Electrospun Scaffold with Sustained Antibacterial and Tissue-Matched Mechanical Properties for Potential Application as Functional Mesh.

INTRODUCTION: Various materials and approaches have been used to reduce the mesh-induced inflammatory response and modify the mesh with tissue-matched mechanical properties, aiming to improve the repair of abdominal wall defects. MATERIALS AND METHODS: In this study, we fabricated a polycaprolactone (PCL)/silk fibroin (SF) mesh integrated with amoxicillin (AMX)-incorporating multiwalled carbon nanotubes (MWCNTs) via electrospinning, grafting and crosslinking, developing a sustainable antibiotic and flexible mesh. AMX was loaded into the hollow tubular MWCNTs by physical adsorption, and a nanofibrous structure was constructed by electrospinning PCL and SF (40:60 w/w). The AMX@MWCNTs were then chemically grafted onto the surfaces of the PCL/SF nanofibers by treating with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) solution for simultaneous crosslinking and coating. The incorporation of AMX into the MWCNTs (AMX@MWCNTs) and the integration of the AMX@MWCNTs with the PCL/SF nanofibers were characterized. Then, the functional mesh was fabricated and fully evaluated in terms of antibacterial activity, mechanical properties and host response. RESULTS: Our results demonstrated that the PCL/SF nanofibrous structure was fabricated successfully by electrospinning. After integrating with AMX@MWCNT by grafting and crosslinking, the functional mesh showed undeformed structure, modified surface hydrophilicity and biocompatible interfaces, abdominal wall-matched mechanical properties, and a sustained-release antibiotic profile in E. coli growth inhibition compared to those of PCL/SF mesh in vitro. In a rat model with subcutaneous implantation, the functional mesh incited less mesh-induced inflammatory and foreign body responses than PCL/SF mesh within 14 days. The histological analysis revealed less infiltration of granulocytes and macrophages during this period, resulting in the loosely packed collagen deposition on the functional mesh and prominent collagen incorporation. DISCUSSION: Therefore, this designed PCL/SF-AMX@MWCNT nanofibrous mesh, functionalized with antibacterial and tissue-matched mechanical properties, provides a promising alternative for the repair of abdominal wall defects.

Evaluation of a Biocomposite Mesh Modified with Decellularized Human Amniotic Membrane for Intraperitoneal Onlay Mesh Repair.

Various materials and approaches have been used to optimize the biocompatibility of mesh to reduce the implant-induced host response in intraperitoneal onlay mesh (IPOM) repair. Ineffective host integration, limited resistance to contamination, and untargeted administration hinder the wider application of the currently available clinical options. In this study, human amniotic membrane (HAM) was decellularized, fully characterized, and compared with porcine small intestinal submucosa (SIS) in terms of its structure, components, and bioactivity. In an in vivo study, HAM was reinforced with silk fibroin (SF) membrane, which was fabricated as a biodegradable submicroscale template by electrospinning, to construct a bilayer composite mesh. The independent SF membrane, associated with HAM and SIS, was evaluated for tissue remodeling in vitro. The HAM-SF and SIS meshes were then characterized morphologically and implanted intraperitoneally into Sprague-Dawley rats for 28 days for macroscopic investigation of their integration into the host via interactions of regulatory factors. After decellularization, HAM formed a bioagent-rich collagen-based acellular structure. HAM was superior to SIS in concurrently suppressing the expression of transforming growth factor ß1 (TGF-ß1) and proangiogenic proliferation. When HAM, SF, and SIS were used as regenerative scaffolds, they showed qualified biocompatibility, cell infiltration, and degradation in vitro. Comparatively, macroscopic observation after implantation indicated that HAM-SF induced less-intensive intraperitoneal adhesion and weaker inflammatory responses at the interface but greater angiogenesis in the explant than SIS. Analysis of the expression of regulatory factors showed a greater quantity of hepatocyte growth factor (HGF) in HAM, which partly inhibited the expression of TGF-ß1 and promoted vascular endothelial growth factor (VEGF)-induced angiogenesis. This bioactive interaction appeared to be responsible for the better host integration, making HAM more biocompatible than SIS in IPOM repair. When combined with SF, HAM displayed similar mechanical properties to SIS. In conclusion, HAM displayed better bioactivity and biocompatibility than SIS. After its reinforcement with SF, HAM-SF is a promising biocomposite mesh for IPOM repair.

Triangle Trocar Configuration in Laparoscopic Totally Extraperitoneal Inguinal Hernia Repair: A Prospective Randomized Controlled Study.

BACKGROUND: In totally extraperitoneal (TEP) operation, when trocars are arranged with midline configuration, operative instruments can easily interfere with each other because of the small operative angle. The triangle trocar configuration, which creates a large operative angle, may minimize interference. Therefore, we evaluated the use of triangle trocar configuration in TEP inguinal hernia repair. METHODS: A prospective randomized controlled study was conducted in 113 patients of laparoscopic TEP inguinal hernia repair in the Department of Hernia and Abdominal Wall Surgery, Shanghai East Hospital, between July 2016 and June 2017. Patients were randomly assigned to TEP laparoscopic inguinal hernioplasty with triangle trocar configuration (study group, n = 59) or midline trocar configuration (control group, n = 54). Perioperative outcomes (operative time, operative complications, postoperative pain, hospital stay, and costs), early postoperative complications (seroma/hematoma and uroschesis), and mid-term outcomes (late postoperative complications and recurrence) were observed and compared. RESULTS: After a mean follow-up of 10.21 ± 2.32 mo, there was no significant difference in operative time, operative complications, postoperative pain, postoperative hospital stay, costs, postoperative complications, and recurrence rate between the two groups. The indirect hernia sac dissection time was shorter in the study group than in the control group. CONCLUSIONS: Triangle trocar configuration in TEP laparoscopic hernia repair is safe and reliable and is an option for hernia surgeons. The technique creates a large operative angle and avoids interference between endo-instruments, which facilitates TEP and decreases the indirect hernia sac dissection time.

Promoting early neovascularization of SIS-repaired abdominal wall by controlled release of bioactive VEGF.

Insufficient early neovascularization post-operation is thought to be the main reason of surgical recurrence of porcine small intestinal submucosa (SIS)-repaired abdominal wall defects. The controlled release of exogenous angiogenic growth factors (GFs) from biocompatible carriers is a possible way to solve this problem. In the present study, dextran nanoparticles (DNPs) loaded with vascular endothelial growth factor 165 (VEGF165) were pre-formulated by dual-aqueous phase separation method and then electrospun into the poly(lactic-co-glycolic acid) (PLGA) polymer fibers. The aim of this material is to release VEGF in a sustained manner with the degradation of PLGA and maintain its bioactivity concurrently. The prepared VEGF/DNPs-PLGA membrane was sandwiched by dual-layer SIS to construct a SIS-DNPs/VEGF-PLGA-SIS (SVDPS) composite scaffold. The in vitro study showed that the VEGF/DNPs-PLGA obtained higher VEGF encapsulation efficiency as well as better release property and bioactivity than the emulsion electrospun VEGF-PLGA and PLGA fibrous membranes by ELISA and HUVEC proliferation. The in vivo study showed that the SVDPS composite scaffold promoted significantly higher early therapeutic neovascularization within 2 weeks post-surgery than SIS-VEGF-PLGA-SIS (SVPS) and SIS-PLGA-SIS (SPS) by immunohistochemical and immunoblotting examination.

Hepatectomy for patients with alveolar echinococcosis: Long-term follow-up observations of 144 cases.

BACKGROUND: Western China is a region in which alveolar echinococcosis (AE) is endemic. Few studies and comparisons have evaluated the outcomes of AE patients after hepatectomy, and no strategy has been defined for the treatment of AE patients with unresectable tumors. This study sought to assess the outcomes of AE patients after hepatectomy at a tertiary referral center. PATIENTS AND METHODS: We retrospectively analyzed data from 144 patients with hepatic AE who were treated via hepatectomy at our center between January 2004 and December 2015. Patients' overall survival (OS), progression-free survival (PFS), and risk factors were analyzed, and Kaplan-Meier survival curves were constructed. Patient age, year of initial treatment, PNM stage, and risk factors were entered as co-variates in a Cox regression modle that was used for analysis. RESULTS: Hepatectomy was performed in 144 patients diagnosed with hepatic AE (84 complete resections and 60 reduction surgeries). In the complete resection group, the 5- and 10-year OS rates were both 97.6%, and the 5- and 10-year PFS rates were both 97.9%. In the reduction surgery group, the 5-, and 10-year OS rates were 89.7% and 73.4%, respectively, and the 5-, and 10-year PFS rates were 78.1% and 69.5%, respectively. Patients in the complete group had better OS prognoses and PFS than patients in the reduction surgery group (P = 0.018 and P = 0.001). Multivariate analysis indicated that curability and portal vein invasion are independent factors associated with PFS (P = 0.028 and P = 0.006). CONCLUSIONS: The most effective therapy for AE is complete resection. Reduction surgery does not appear to offer obvious advantages over benzimidazole therapy alone in the treatment of AE. Curability and portal vein invasion are independent prognostic factors for PFS in a multivariate analysis.

Hepatocellular carcinoma cases with high levels of c-Raf-1 expression may benefit from postoperative adjuvant sorafenib after hepatic resection even with high risk of recurrence.

BACKGROUND AND AIMS: Liver resection combined with postoperative sorafenib to prevent recurrence remains a controversial approach for cases of hepatocellular carcinoma (HCC), especially cases with a high risk of recurrence. This study aimed to investigate the efficacy and safety of liver resection combined with sorafenib for HCC with a high risk of recurrence. RESULTS: Most of the cases of HCC were caused by hepatitis B virus (HBV) infection (23 cases, 92%). Most of these tumors (21 cases, 84%) were stage III according to the TNM staging system (12 cases with IIIa, 9 cases with IIIb). In the months after hepatic resection, 19 of the 25 cases (76%) were diagnosed with HCC recurrence or metastasis. Based on the tumor histological biomarker grading system, the group with higher expression levels of c-Raf-1 showed significantly longer overall survival than the group with lower expression of c-Raf-1 (P = 0.012). However, the long-term tumor-free survival advantage disappeared (P = 0.061). Univariate and multivariate analyses indicated that higher expression of c-Raf-1 was significantly associated with better overall survival (hazard ratio [HR]: 1.842; 95% confidence interval [CI]: 1.211-2.542; P = 0.031) and tumor-free survival (HR: 1.319; 95% CI: 1.017-1.543; P = 0.046) in HCC patients who underwent radical hepatic resection. PATIENTS AND METHODS: We retrospectively collected 25 HCC cases with a high risk of recurrence who underwent radical liver resection and who took sorafenib postoperatively from Jan 2010 to Dec 2012. Factors that might contribute to tumor recurrence and treatment failure such as clinical factors, tumor features, and molecular biomarkers were included in our analysis. CONCLUSIONS: HCC patients with a high risk of post-hepatic resection recurrence may benefit from postoperative sorafenib administered as an adjuvant therapy, especially in cases with high levels of c-Raf-1 expression on histological examination.

Host tissue integration process in abdominal wall defect repair: a comparison of two porcine-derived grafts in a long-term study.

BACKGROUND: The aim of this study was to compare the host tissue integration process and biomechanical behaviour after implantation of porcine small intestine submucosa (PSIS) and porcine acellular dermal matrix (PADM) grafts in a rat abdominal wall defect model during a long-term follow-up of 360 days. OBJECTIVES: Full-thickness abdominal wall defects were created in 40 Sprague-Dawley rats and repaired with either PSIS or PADM grafts. Rats were sacrificed at 14, 30, 90 and 360 days to evaluate the presence of herniation, infection, adhesions and changes in thickness and strength properties of the regenerated tissue at the defect site. Histopathology and immunohistochemistry were performed to evaluate the host tissue integration process assessed by the level of collagen deposition, vascularization and inflammatory host sub-chronic and chronic responses. RESULTS: PADM grafts had greater strength in vitro (p < 0.01). Moreover, the strength of the PADM grafts integrated with the surrounding host tissues was greater than that of the PSIS grafts at 360 days postimplantation (p < 0.05). A stronger integration into the host tissue was observed for the PADM grafts, which showed oriented bands of collagen deposition intermixed with similar newly formed blood vessels compared to that of PSIS grafts after 360 days. The PADM grafts showed slower infiltration of macrophages but developed into a more heavily infiltrated tissue compared to the PSIS grafts (p < 0.05). The level of leukocyte infiltration after implantation was similar in both grafts (p > 0.05). CONCLUSION: PADM grafts exhibit more delayed but also more effective host integration than PSIS grafts during the 360 days following implantation, supporting the development of more robust abdominal wall strength.

Carbon nanotubes as VEGF carriers to improve the early vascularization of porcine small intestinal submucosa in abdominal wall defect repair.

Insufficient early vascularization in biological meshes, resulting in limited host tissue incorporation, is thought to be the primary cause for the failure of abdominal wall defect repair after implantation. The sustained release of exogenous angiogenic factors from a biocompatible nanomaterial might be a way to overcome this limitation. In the study reported here, multiwalled carbon nanotubes (MWNT) were functionalized by plasma polymerization to deliver vascular endothelial growth factor165 (VEGF165). The novel VEGF165-controlled released system was incorporated into porcine small intestinal submucosa (PSIS) to construct a composite scaffold. Scaffolds incorporating varying amounts of VEGF165-loaded functionalized MWNT were characterized in vitro. At 5 weight percent MWNT, the scaffolds exhibited optimal properties and were implanted in rats to repair abdominal wall defects. PSIS scaffolds incorporating VEGF165-loaded MWNT (VEGF-MWNT-PSIS) contributed to early vascularization from 2-12 weeks postimplantation and obtained more effective collagen deposition and exhibited improved tensile strength at 24 weeks postimplantation compared to PSIS or PSIS scaffolds, incorporating MWNT without VEGF165 loading (MWNT-PSIS).

Repair of abdominal wall defects in vitro and in vivo using VEGF sustained-release multi-walled carbon nanotubes (MWNT) composite scaffolds.

OBJECTIVE: Porcine acellular dermal matrices (ADM) have been widely used in experimental and clinical research for abdominal wall repair. Compared to porcine small intestinal submucosa (SIS), the effect of these matrices on the regenerative capacity of blood vessels is still not ideal. Multi-walled carbon nanotubes (MWNTs) can more effectively transport VEGF to cells or tissues because of their large specific surface area and interior cavity. In this study, we explored the safety and efficacy of implanted VEGF-loaded MWNT composite scaffolds in vitro and vivo to repair abdominal wall defects. MATERIALS AND METHODS: VEGF-loaded MWNTs were prepared by a modified plasma polymerization treatment. Four composite scaffolds were evaluated for cytotoxicity, proliferation, and release dynamics. We created 3 cm×4 cm abdominal wall defects in 43 Sprague-Dawley rats. After implantation times of 2, 4, 8, and 12 weeks, the scaffolds and the surrounding tissues were collected and examined by gross inspection, biomechanical testing, and histological examination. RESULTS: A 5-10 nm poly(lactic-co-glycolic acid) (PLGA) film was evenly distributed on MWNTs. The 3% MWNT composite group showed lower cytotoxicity and appropriate release performance, and it was thus tested in vivo. In rats with the 3% composite implanted, host cells were prevented from migrating to the ADM at 2 weeks, vascularization was established more rapidly at 12 weeks, and the values for both the maximum load and the elastic modulus were significantly lower than in the ADM-alone group (p<0.01). Histological staining revealed that the MWNT was still not completely eliminated 12 weeks after implantation. CONCLUSION: MWNTs were able to carry VEGF to cells or tissues, and the 3% MWNT composite material showed lower cytotoxicity and had an appropriate release performance, which prompted faster vascularization of the ADM than other scaffolds. Nevertheless, the MWNTs induced harmful effects that should be carefully considered in biomedical studies.