Colonization of Klebsiella pneumoniae inside fistula tracts: a possible risk factor for failure of fibrin glue-assisted closure.

GOALS: This study was designed to investigate the risk factors affecting glue-assisted closure (GAC) in the enterocutaneous fistula (ECF) patients receiving glue application. BACKGROUND: ECF is a challenging problem in surgical practice, and it is difficult to resolve by spontaneous closure. Currently, GAC is popular when treating fistulas, but data related to risk factors are limited. METHODS: We retrospectively analyzed 82 patients with 93 ECFs, who had autologous glue sealing from 2010 to 2012 in a referral center. Their demographic data, clinical records, and fistula characteristics were collected. Both univariate analysis and multivariate Cox proportional hazards model were used to determine the prognostic factors affecting closure. RESULTS: During the 14-day treatment period, 78.5% (73/93) of the fistulas achieved GAC. We excluded 3 reopened fistulas and investigated 90 ECFs from 79 patients. Univariate analysis demonstrated that patients with high levels of CRP, high CRP:prealbumin ratio, elevated blood glucose, and specific pathogen colonization, together with lower GI location, greater output volume, and shorter tract length, had a poor outcome (P<0.05). Using multivariate analysis, monomicrobial and polymicrobial colonization with Klebsiella pneumoniae inside the fistula tracts (hazard ratio, 0.191; 95% confidence interval, 0.045-0.810; P=0.025) was a statistically significant risk factor for failure of fistula closure. CONCLUSIONS: The presence of monomicrobial and polymicrobial colonization with K. pneumoniae in fistulous tracts was an independent risk factor for failure of GAC in patients receiving glue application. Better debridement of the tracts should be performed before the glue sealing.

Establishment and evaluation of an improved rat model of open abdomen.

INTRODUCTION: This study aimed to establish an animal model of open abdomen (OA) through temporary abdominal closure via different techniques. METHODS: Adult male Sprague-Dawley rats were randomly divided into three groups: group A (OA with polypropylene mesh alone); group B (OA with polypropylene mesh combined with a patch); and group C (OA with polypropylene mesh and a sutured patch). Vital signs, pathophysiological changes, and survival rates were closely monitored in the rats for 7 days after surgery. Abdominal X-rays and histopathological examinations were performed to assess abdominal organ changes and wound healing. RESULTS: The results showed no significant difference in mortality rates among the three groups (p > 0.05). However, rats in group B exhibited superior overall condition, cleaner wounds, and a higher rate of wound healing compared to the other groups (p < 0.05). Abdominal X-rays indicated that varying degrees of distal intestinal obstruction in all groups. Histopathological examinations revealed fibrous hyperplasia, inflammatory cell infiltration, neovascularization, and collagen deposition in all groups. Group B demonstrated enhanced granulation tissue generation, neovascularization, and collagen deposition compared to the other groups (p < 0.05). CONCLUSIONS: Polypropylene mesh combined with patches is the most suitable method for establishing an animal model of OA. This model successfully replicated the pathological and physiological changes in postoperative patients with OA, specifically the progress of abdominal skin wound healing. It provides a practical and reliable animal model for OA research.

Hybrid Double-Sided Tape with Asymmetrical Adhesion and Burst Pressure Tolerance for Abdominal Injury Treatment.

Patients with open abdominal (OA) wounds have a mortality risk of up to 30%, and the resulting disabilities would have profound effects on patients. Here, we present a novel double-sided adhesive tape developed for the management of OA wounds. The tape features an asymmetrical structure and employs an acellular dermal matrix (ADM) with asymmetric wettability as a scaffold. It is constructed by integrating a tissue-adhesive hydrogel composed of polydopamine (pDA), quaternary ammonium chitosan (QCS), and acrylic acid cross-linking onto the bottom side of the ADM. Following surface modification with pDA, the ADM would exhibit characteristics resistant to bacterial adhesion. Furthermore, the presence of a developed hydrogel ensures that the tape not only possesses tissue adhesiveness and noninvasive peelability but also effectively mitigates damage caused by oxidative stress. Besides, the ADM inherits the strength of the skin, imparting high burst pressure tolerance to the tape. Based on these remarkable attributes, we demonstrate that this double-sided (D-S) tape facilitates the repair of OA wounds, mitigates damage to exposed intestinal tubes, and reduces the risk of intestinal fistulae and complications. Additionally, the D-S tape is equally applicable to treating other abdominal injuries, such as gastric perforations. It effectively seals the perforation, promotes injury repair, and prevents the formation of postoperative adhesions. These notable features indicate that the presented double-sided tape holds significant potential value in the biomedical field.

Whole Model Path Planning-Guided Multi-Axis and Multi-Material Printing of High-Performance Intestinal Implantable Stent.

The problems of step effects, supporting material waste, and conflict between flexibility and toughness for 3D printed intestinal fistula stents are not yet resolved. Herein, the fabrication of a support-free segmental stent with two types of thermoplastic polyurethane (TPU) using a homemade multi-axis and multi-material conformal printer guided with advanced whole model path planning is demonstrated. One type of TPU segment is soft to increase elasticity, and the other is used to achieve toughness. Owing to advancements in stent design and printing, the obtained stents present three unprecedented properties compared to previous three-axis printed stents: i) Overcoming step effects; ii) Presenting comparable axial flexibility to a stent made of a single soft TPU 87A material, thus increasing the feasibility of implantation; and iii) Showing equivalent radial toughness to a stent made of a single hard TPU 95A material. Hence, the stent can resist the intestinal contractive force and maintain intestinal continuity and patency. Through implanting such stents to the rabbit intestinal fistula models, therapeutic mechanisms of reducing fistula output and improving nutritional states and intestinal flora abundance are revealed. Overall, this study develops a creative and versatile method to improve the poor quality and mechanical properties of medical stents.

Multifunctional Electrospun Textiles for Wound Healing.

The novel multifunctional electrospun textiles were fabricated by incorporating sheet-like kaolinite and silver nanoparticles (AgNps) into a polyurethane (PU) textile by using electrostatic spinning to promote wound-healing process. Threedimensional network of PU electrospun textiles offered an appropriate framework for loading kaolinite nanosheets and AgNps. Moreover, the kaolinite nanosheets healed bleeding wounds by accelerating plasma absorption, increasing blood cell concentrations, and stimulating coagulation factors. Furthermore, the AgNps killed microbes by destroying the cell membrane, while the deleterious effects were controlled by incorporation into the electrospun textile. The therapeutic effects of multifunctional electrospun textile in treating full-thickness abdominal wall defect were explored. The wound healing process could be accelerated via the textile by restoring the abdominal physiological environment, reducing the inflammatory response, and promoting collagen deposition, angiogenesis, and epithelization.

The effect of different temporary abdominal closure materials on the growth of granulation tissue after the open abdomen.

BACKGROUND: Temporary abdominal closure (TAC) is often performed after an open abdomen to prevent postoperative complications. Reducing the time of TAC and performing a skin grafting as early as possible would improve the outcome of open abdomen. This study was designed to evaluate the effects of different TAC materials and topically applied exogenous growth factors on the growth of granulation tissue covered on the wound areas after the open abdomen. METHODS: Healthy Sprague-Dawley rats were randomly assigned to four groups of six animals each. Twenty-four hours after induction of peritonitis and intra-abdominal hypertension by intraperitoneal injection of nitrogen, relaparotomies were done. The abdomen was then closed with polyethylene sheet or polypropylene mesh plus growth factor (or not). On the seventh day after TAC surgery, TAC materials were removed, and granulation tissue on the wound surface was assessed microscopically. Microvascular densities, thickness of granulation tissue, and fibroblast counts were also measured. RESULTS: Microvascular densities, thickness of granulation tissue, and fibroblast counts were the highest for polypropylene mesh closure plus recombinant bovine basic fibroblast growth factor (rbFGF) followed by polypropylene mesh plus recombinant human growth hormone (rhGH) and polypropylene mesh alone, with polyethylene sheet alone being the least. CONCLUSIONS: Polypropylene mesh could promote the growth of granulation tissue after the open abdomen. Topical application of rhGH or rbFGF further hastens the process, with the effect of rbFGF being the greatest.

Fabrication of gelatin-based printable inks with improved stiffness as well as antibacterial and UV-shielding properties.

Gelatin-based inks have a broad range of applications in bioprinting for tissue engineering and regenerative medicine due to their biocompatibility, ease of modification, degradability, and rapid gelation induced by low temperature. However, gelatin-derived inks prepared through low-temperature treatment have poor mechanical properties that limit their applications. To solve this problem, we designed polyacrylamide/gelatin/silver nanoparticle (PAAm-GelatinAgNPs) ink to improve gelatin-based hydrogels. The ink is based on double networks, in which the physically cross-linked gelatin as the first network and covalently cross-linked PAAm as the second network. It was found that the presence of PAAm increased the tensile and compression strength of the gelatin-based ink. Moreover, silver nanoparticles endowed the antibacterial properties to the gelatin-based ink and were able to shield the UV irradiation and damages to rat skin. In addition, this ink showed the shear thinning property; Consequently it succeeded in printing complex 3D scaffolds such as the cube, five-pointed star, flower, and university logo of "SEU". In summary, this ink presents a new strategy for the modification of gelatin and offers new potential applications for customized therapy of antimicrobial and anti-UV damage to tissues.

Biomaterials and biosensors in intestinal organoid culture, a progress review.

As an emerging technology, intestinal organoids are promising new tools for basic and translational research in gastroenterology. Currently, culture of intestinal organoids relies mostly on a type of tumor-derived scaffolds, namely Matrigel, which may pose tumorigenic risks to organoid implantation. Apart from the traditional detection methods, such as tissue slicing and fluorescence staining, the monitoring of intestinal organoids requires real-time biosensors that can adapt to their three-dimensional dynamic growth patterns. In this review, we summarized the recent advances in developing definite hydrogel scaffolds for intestinal organoid culture and identified key parameters for scaffold design. In addition, classified by different substrate compositions like pH, electrolytes, and functional proteins, we concluded the existing live-imaging biosensors and elucidated their underlying mechanisms. We hope this review enhances the understanding of intestinal organoid culture and provides more practical approaches to investigate them.

Engineering an adhesive based on photosensitive polymer hydrogels and silver nanoparticles for wound healing.

Hemostasis, wound closure and prevention of infection are critical to wound healing after an injury. Skin adhesives have been used to seal incisions, thus aiding primary wound healing, as well as creating a barrier to microbes. We constructed a skin adhesive with antibacterial and hemostatic activities (AHAs) for wound management. The adhesive was made by using methacrylated hyaluronan-polyacrylamide (MHA-PAAm) hydrogels, integrated with silver nanoparticles (AgNPs) and bonded to gelatin. Because of the three-dimensional network structure of the hydrogels, nanoscale particles can be encapsulated into their voids; the AgNPs, through sustained delivery of silver ions, endow the adhesives with sustained broad-spectrum antibacterial activity. Furthermore, due to the introduction of MHA which can be crosslinked by visible light, the polyacrylamide hydrogel matrix can be formed through photo crosslinking. In addition, gelatin can be bonded to both the hydrogel matrix and host tissues because of the interaction between carboxyl and amino-moieties. Our animal studies demonstrated that the AHAs which possess tissue adhesive and antibacterial properties were easy to stretch, and were able to stop bleeding in rat tail amputation and liver injury models. AHAs enhance wound granulation tissue formation, vascular tissue formation, and collagen formation, as well as alleviate inflammation. These properties promoted wound closure in rat wound infection models, promising great potential for applying AHAs in clinical uses.

Application of a 3D-printed "fistula stent" in plugging enteroatmospheric fistula with open abdomen: A case report.

BACKGROUND: Open abdomen (OA) has been generally accepted for its magnificent superiority and effectiveness in patients with severe trauma, severe intra-abdominal infection, and abdominal compartment syndrome. In the meantime, OA calls for a mass of nursing and the subsequent enteroatomospheric fistula (EAF), which is one of the most common complications of OA therapy, remains a thorny challenge. CASE SUMMARY: Our team applied thermoplastic polyurethane as a befitting material for producing a 3D-printed "fistula stent" in the management of an EAF patient, who was initially admitted to local hospital because of abdominal pain and distension and diagnosed with bowel obstruction. After a series of operations and OA therapy, the patient developed an EAF. CONCLUSION: Application of this novel "fistula stent" resulted in a drastic reduction in the amount of lost enteric effluent and greatly accelerated rehabilitation processes.

AuNPs-PCL nanocomposite accelerated abdominal wound healing through photothermal effect and improving cell adhesion.

Accelerating wound healing with modified biomaterial has been an attracting field in both material science and medicine. Enhanced cell adhesion could be acquired by improving surface hydrophilicity, which contributes to accelerating wound healing. Chemical reaction has been used for surface modification, but this study used a simple and nontoxic method to improve the hydrophilicity. Polycaprolactone (PCL) scaffold has been regarded as promising material for wound healing while its surface is hydrophobic. Our study demonstrated enhanced hydrophilicity of PCL with AuNPs coating. AuNPs has good biocompatibility and excellent photothermal effect. The coating of AuNPs not only improved the cell adhesion, but also gave PCL the ability to inhibit the growth of bacteria. Animal study showed that the nanocomposites decreased lymphocytes and neutrophils, increased neovascularization and accelerated the abdominal wound healing, which was attributed to improved hydrophilicity and the antibacterial ability. In conclusion, we demonstrated that the nanocomposite could be used as a potential scaffold for cell adhesion and wound healing, and the role of AuNPs was highlighted as a kind of outstanding supplement.

Novel in situ forming hydrogel based on xanthan and chitosan re-gelifying in liquids for local drug delivery.

Injectable hydrogels have been an attractive topic in biomaterials. However, during gelation in vivo, they are easy to disperse due to tissue exudates, thus leading to failure of controlled drug release. To solve this problem, we present a novel polysaccharide-based injectable hydrogel via self-crosslinking of aldehyde-modified xanthan (Xan-CHO) and carboxymethyl-modified chitosan (NOCC). The physical properties were optimized by adjusting the mass ratio of Xan-CHO and NOCC. Experiments revealed that this material exhibited the characteristics of self-healing, anti-enzymatic hydrolysis, biocompatibility and biodegradability. The releasing curve demonstrated stable release of BSA-FITC within 10 h after injection in liquids. After incorporation with a vascular endothelial growth factor, there was an interaction between this biomaterial and the host, which accelerated the reconstruction of the abdominal wall in rats. Therefore, this injectable hydrogel, as a drug delivery system, can prevent drug outburst in a variety of settings and function as a tissue scaffold.

Tunable sequential drug delivery system based on chitosan/hyaluronic acid hydrogels and PLGA microspheres for management of non-healing infected wounds.

Treatment of non-healing infected wounds is an arduous task in clinical practice. Early antibacterial strategy and subsequent promotion of granulation tissue growth facilitate to cure the wounds. For this purpose, we fabricated a sequential drug delivery system by incorporation of an injectable hydrogel with porous PLGA microspheres. Vancomycin was linked to the injectable hydrogel via the reversible Schiff's base reaction, and VEGF were encapsulated into PLGA microspheres. After adding vancomycin, the strength and elasticity of the hydrogel were improved, and the gelation time was shortened. The results also demonstrated that the releasing profile of vancomycin was pH-dependent and the VEGF's profile was adjustable by changing the pore sizes of PLGA microspheres. The duration of VEGF release was longer than vancomycin. This hybrid system was valid to inhibit bacteria growth and accelerate vein endothelial cell proliferation in vitro. In rat models, it was effective to manage non-healing infected wounds by reducing inflammation and promoting angiogenesis. In conclusion, this sequential delivery system is promoting to manage non-healing infected wounds, and also provides a new thought to realize the staged drug release.

Fibrin sealant prevents gastrointestinal anastomosis dehiscence in intra-abdominal sepsis.

We observed the potential use of fibrin sealant as a therapeutic modality for successful resolution of gastrointestinal anastomosis dehiscence in intra-abdominal sepsis. Forty-eight patients (33 men and 15 women) suffering from intra-abdominal sepsis were subjected to prophylactic appliance of fibrin sealant during immediate primary anastomosis during the laparotomy. The perioperative management invariably involved fluid resuscitation, active suction drainage of the abdominal liquor puris, nutritional supplementation, and growth hormone. The total surgical-related success ratio was 91.7% (44/48) for primary anastomosis with fibrin sealant in intra-abdominal sepsis. Anastomotic leakage occurred in the other four patients, two of which died because of leakage complications in our hospital. The hospital stay after the operation was 30.2 +/- 12.0 days. There has been no sign of recurrence over a follow-up period of 1-15 months. It is concluded that fibrin sealant may be useful in preventing gastrointestinal anastomosis dehiscence in intra-abdominal sepsis.

Tannin-based adhesive for protection of colonic anastomosis in the open abdomen.

This study was aimed to evaluate the effect of tannin acid- polyethylene glycol (TP) adhesive on the wound healing process of primary colonic anastomosis in the open abdomen (OA). Adhesion strength test, degradation and hemostatic ability of TP were investigated. In a rat model, after standard colonic anastomoses, rats were divided into three groups: OA group; OA + FG (fibrin glue) group; OA + TP group. Five days after surgery, body weight, anastomotic bursting pressure (ABP), and histology of anastomotic tissue were evaluated. Performance of adhesion strength and hemostatic ability of TP was better than that of FG. The weight of TP decreased by over 50% after 11-day incubation. All rats survived well after surgery. Compared to OA group and OA + FG group, OA + TP group showed a significant improvement in body weight, ABP and healing state. Application of TP adhesive, used as an auxiliary treatment of colonic anastomosis operation, improved the wound strength and promoted the anastomotic healing after OA.

Injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for abdominal tissue regeneration.

Abdominal wall defect caused by open abdomen (OA) or abdominal trauma is a serious issue since it induces several clinical problems. Although a variety of prosthetic materials are commonly employed, complications occur including host soft tissue response, fistula formation and chronic patient discomfort. Recently, abundant natural polymers have been used for injectable hydrogel synthesis in tissue regeneration. In this study, we produced the chitosan - hyaluronic acid (CS/HA) hydrogel and investigated its effects on abdominal tissue regeneration. The physical and biological properties of the hydrogel were demonstrated to be suitable for application in abdominal wounds. In a rat model simulating open abdomen and large abdominal wall defect, rapid cellular response, sufficient ECM deposition and marked neovascularization were found after the application of the hydrogel, compared to the control group and fibrin gel group. Further, the possible mechanism of these findings was studied. Cytokines involved in angiogenesis and cellular response were increased and the skew toward M2 macrophages credited with the functions of anti-inflammation and tissue repair was showed in CS/HA hydrogel group. These findings suggested that CS/HA hydrogel could prevent the complications and was promising for abdominal tissue regeneration.

An Injectable, Wound-Adapting, Self-Healing Hydrogel for Fibroblast Growth Factor 2 Delivery System in Tissue Repair Applications.

Rapid wound healing is a fundamental health concern and poses a critical challenge for healthcare systems worldwide. Here, we developed an injectable, dynamic, self-healing hydrogel serving as a fibroblast growth factor 2 (FGF2) delivery system for tissue repair applications. Benzaldehyde-terminated polyethylene glycol (BAPEG) was synthesized and cross-linked with N-Succinyl-chitosan (SCS) through reversible Schiff-base reaction to form a dynamic self-healing hydrogel. Because it can be injected after gelation and self-heal into an integral part, the hydrogel could not only auto-adapt to the irregular wound surface to provide better protection but also encapsulate drugs homogeneously and implant into tissue with a less invasive strategy. As a result, the FGF2-loaded SCS/BAPEG hydrogel is able to significantly promote the process of angiogenesis, collagen deposition, and granulation tissue formation, as well as reduce inflammation. This study opens the door to self-healing hydrogels serving as a drug delivery system for tissue repair applications.

Evaluation of polypropylene mesh coated with biological hydrogels for temporary closure of open abdomen.

Polypropylene mesh, as a temporary abdominal closure device, may cause mechanical intestine injury and inflammatory response. Chitosan/gelatin hydrogel has excellent biocompatibility, soft and elastic properties. This work is to assess the effects of the chitosan/gelatin hydrogel coated polypropylene mesh on open abdomen wounds. Histological analysis and detection of healing-related factors were conducted to evaluate the inflammation and wound healing process. After 1-day implantation in a murine model of open abdomen, the coated polypropylene mesh, compared with simple polypropylene mesh, demonstrated well protection of the intestine serosa. After 14-day implantation, it reduced the inflammation response by down-regulating the cytokines interleukin-6 and tumor necrosis factor-α, and up-regulating the anti-inflammatory factor interleukin-10. Meanwhile, the composite stimulated granulation tissue growth, and promoted matrix deposition and angiogenesis after 7 and 14 days. In conclusion, the modified temporary abdominal closure composite could significantly protect the intestines from mechanical damage and accelerate wound healing.

Evaluating the use of fibrin glue for sealing low-output enterocutaneous fistulas: study protocol for a randomized controlled trial.

BACKGROUND: The management of an enterocutaneous fistula poses a significant challenge to surgeons and is often associated with a costly hospital stay and long-term discomfort. The use of fibrin glue in the fistula tract has been shown to promote closure of low output enterocutaneous fistulas. Our previous nonrandomized study demonstrated that autologous platelet-rich fibrin glue treatment significantly decreased time to fistula closure and promoted closure rates. However, there are several limitations in the study, which may lead to bias in our conclusion. Thus, a multicenter, randomized, controlled clinical trial is required. METHODS/DESIGN: The study is designed as a randomized, open-label, three-arm, multicenter study in nine Chinese academic hospitals for evaluating the efficacy and safety of fibrin glue for sealing low-output fistulas. An established number of 171 fistula patients will undergo prospective random assignment to autologous fibrin glue, commercial porcine fibrin sealants or drainage cessation (1:1:1). The primary endpoint is fistula closure time (defined as the interval between the day of enrollment and day of fistula closure) during the 14-day treatment period. DISCUSSION: To our knowledge, this is the first study to evaluate the safety and efficacy of both autologous and commercial fibrin glue sealing for patients with low-output volume fistulas. TRIAL REGISTRATION: NCT01828892 . Registration date: April 2013.

Protection of colonic anastomosis with platelet-rich plasma gel in the open abdomen.

BACKGROUND: Although evidence for colonic anastomosis in the damage control abdomen continues to accumulate, anastomotic leak is common and associated with greater morbidity. The purposes of our study was to evaluate the effect of platelet-rich plasma (PRP) gel on the healing of colon anastomosis and anastomotic strength in the open abdomen. METHODS: PRP was prepared by enriching whole blood platelet concentration from healthy rat. In the rodent model, standard colonic anastomoses followed by closure of abdomen (Control; n=10) and anastomoses followed by open abdomen (OA; n=10) were compared to PRP-sealed anastomoses in open abdomen (OA+PRP; n=10). One week after surgery, body weight, anastomotic bursting pressure, hydroxyproline concentration, and histology of anastomotic tissue were evaluated. RESULTS: All rats survived surgery and had no signs of anastomotic leakage. Compared with the control and PRP group, OA group exhibited a significant decrease in body weight, anastomotic bursting pressure, hydroxyproline concentration, and collagen deposition. No significant difference was detected in these variables between the PRP group and the control group. CONCLUSION: PRP gel application prevented delayed anastomotic wound healing after open abdomen, which suggested that anastomotic sealing with PRP gel might improve outcome of colonic injuries in the setting of open abdomen.