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Wiebe A, Hagemeister K, Fayyazi A, Apitzsch J, Lamadé W. Polyurethane-based tissue adhesive for sealing pancreatic anastomosis: a pig model. Surg Endosc 2025:10.1007/s00464-025-11802-5. [PMID: 40410619 DOI: 10.1007/s00464-025-11802-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Accepted: 05/06/2025] [Indexed: 05/25/2025]
Abstract
BACKGROUND Pancreatic anastomosis is a critical step in partial pancreatoduodenectomy, as failure of the anastomosis with postoperative pancreatic fistula can lead to high morbidity and mortality. While various fibrin-based sealing agents have been tested, their effectiveness is limited due to rapid degradation by pancreatic secretions. This study aimed to evaluate the applicability and biocompatibility of a novel biodegradable, polyurethane-based adhesive (VIVO 120™) for intraoperative sealing of pancreatic anastomoses in a long-term survival pig model. METHODS An in vitro investigation of VIVO 120™ resistance to pancreatic enzymes over 21 days and an in vivo application for sealing a simplified pancreatogastrostomy were conducted. Following pancreatic tail resection, a simplified pancreatogastrostomy was performed in 12 pigs, sealing the anastomosis between the pancreatic body and the gastric wall with VIVO 120™. One pig underwent acute testing (1-day survival), and 11 pigs were included in a long-term survival study (14-day survival). Animals were divided into three groups based on adhesive application: Group 1 (intraluminal application, n = 4), Group 2 (extraluminal application, n = 3), and Group 3 (intraluminal application with pancreatic duct obstruction and superficial pressure injection into the pancreatic resection plane, n = 4). Clinical observations, laboratory diagnostics, necropsy, and histological analyses were performed. RESULTS VIVO 120™ exhibited high resistance to enzymatic degradation. Histology revealed no adhesive remnants in Group 1, whereas in Group 2, the adhesive was integrated into the surrounding connective tissue. Both groups showed signs of only very mild pancreatitis distant to the adhesive, likely resulting from surgical trauma, and no signs of pancreatic fistula, while Group 3 exhibited severe pancreatitis and extensive fibroblastic proliferation following pressure application. CONCLUSION VIVO 120™ is biocompatible and resistant to pancreatic secretions, suggesting its potential for effective sealing of pancreatic anastomoses. However, application with pressure into pancreatic tissue should be avoided to prevent severe pancreatitis and extensive fibroblastic proliferation.
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Affiliation(s)
- Anna Wiebe
- Department of Vascular Surgery, Klinikum Esslingen, Hirschlandstraße 97, 73730, Esslingen, Germany.
| | - Kerstin Hagemeister
- Universitätsklinikum Bonn, Haus für Experimentelle Therapie, Venusberg-Campus, Bonn, Germany
| | - Afshin Fayyazi
- SYNLAB Institute for Pathology and Molecular Pathology Pforzheim, Pforzheim, Germany
| | - Jonas Apitzsch
- Department of Radiology, Helios Klinikum Pforzheim, Pforzheim, Germany
| | - Wolfram Lamadé
- Department of General, Visceral and Vascular Surgery, Helios Klinikum Pforzheim, Pforzheim, Germany
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Cheng X, Zhang Z, Ren H, Zou Z, Zhang Y, Qu Y, Chen X, Zhao J, He C. A low-swelling hydrogel as a multirole sealant for efficient dural defect sealing and prevention of postoperative adhesion. Natl Sci Rev 2024; 11:nwae160. [PMID: 38867893 PMCID: PMC11168225 DOI: 10.1093/nsr/nwae160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 03/30/2024] [Accepted: 04/28/2024] [Indexed: 06/14/2024] Open
Abstract
Dural defects and subsequent complications, including cerebrospinal fluid (CSF) leakage, are common in both spine surgery and neurosurgery, and existing clinical treatments are still unsatisfactory. In this study, a tissue-adhesive and low-swelling hydrogel sealant comprising gelatin and o-phthalaldehyde (OPA)-terminated 4-armed poly(ethylene glycol) (4aPEG-OPA) is developed via the OPA/amine condensation reaction. The hydrogel shows an adhesive strength of 79.9 ± 12.0 kPa on porcine casing and a burst pressure of 208.0 ± 38.0 cmH2O. The hydrogel exhibits a low swelling ratio at physiological conditions, avoiding nerve compression in the limited spinal and intracranial spaces. In rat and rabbit models of lumbar and cerebral dural defects, the 4aPEG-OPA/gelatin hydrogel achieves excellent performance in dural defect sealing and preventing CSF leakage. Moreover, local inflammation, epidural fibrosis and postoperative adhesion in the defect areas are markedly reduced. Thus, these findings establish the strong potential of the hydrogel sealant for the effective watertight closure of dural defects.
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Affiliation(s)
- Xueliang Cheng
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- Department of Orthopedics, The Second Norman Bethune Hospital of Jilin University, Changchun 130014, China
| | - Zhen Zhang
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
| | - Hui Ren
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
| | - Zheng Zou
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
| | - Yu Zhang
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
| | - Yang Qu
- Department of Orthopedics, The Second Norman Bethune Hospital of Jilin University, Changchun 130014, China
| | - Xuesi Chen
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
| | - Jianwu Zhao
- Department of Orthopedics, The Second Norman Bethune Hospital of Jilin University, Changchun 130014, China
| | - Chaoliang He
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
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Ren H, Zhang Z, Cheng X, Zou Z, Chen X, He C. Injectable, self-healing hydrogel adhesives with firm tissue adhesion and on-demand biodegradation for sutureless wound closure. SCIENCE ADVANCES 2023; 9:eadh4327. [PMID: 37585520 PMCID: PMC10431709 DOI: 10.1126/sciadv.adh4327] [Citation(s) in RCA: 102] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 07/14/2023] [Indexed: 08/18/2023]
Abstract
Tissue adhesives have garnered extensive interest as alternatives and supplements to sutures, whereas major challenges still remain, including weak tissue adhesion, inadequate biocompatibility, and uncontrolled biodegradation. Here, injectable and biocompatible hydrogel adhesives are developed via catalyst-free o-phthalaldehyde/amine (hydrazide) cross-linking reaction. The hydrogels demonstrate rapid and firm adhesion to various tissues, and an o-phthalaldehyde-mediated tissue adhesion mechanism is established. The hydrogel adhesives show controlled degradation profiles of 6 to 22 weeks in vivo through the incorporation of disulfide bonds into hydrogel network. In liver and blood vessel injury, the hydrogels effectively seal the incisions and rapidly stop bleeding. In rat and rabbit models of full-thickness skin incision, the hydrogel adhesives quickly close the incisions and accelerate wound healing, which exhibit efficacies superior to those of commercially available fibrin glue and cyanoacrylate glue. Thus, the hydrogel adhesives show great potential for sutureless wound closure, hemostasis sealing, and prevention of leakage in surgical applications.
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Affiliation(s)
- Hui Ren
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Zhen Zhang
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
| | - Xueliang Cheng
- Department of Spinal Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130014, China
| | - Zheng Zou
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Xuesi Chen
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China
| | - Chaoliang He
- CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
- School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China
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Lake SP, Bradbury K, Gagne DH, Deeken CR, Badhwar A, Bohnen A. Efficacy of Flowable Collagen Hemostat Evaluated in Preclinical Models of Liver Injury and Spinal Cord Exposure. MEDICAL DEVICES-EVIDENCE AND RESEARCH 2023; 16:123-132. [PMID: 37304735 PMCID: PMC10257272 DOI: 10.2147/mder.s411735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 05/29/2023] [Indexed: 06/13/2023] Open
Abstract
Introduction Excessive bleeding in trauma and surgical settings leads to increased operative time, reoperation rates, and overall healthcare costs. A wide range of hemostatic agents have been developed to control bleeding that can vary considerably in type of hemostatic action, ease of application, cost, risk of infection, and dependence on patient coagulation. Microfibrillar collagen-based hemostatic materials (MCH) have yielded beneficial results in a variety of applications. Methods A new flowable collagen product, containing a modified MCH flour, but in a more convenient flowable delivery system, was evaluated for hemostatic efficacy in preclinical models of solid organ injury and spinal cord exposure. The primary objective of this study was to compare the hemostatic potential and local tissue responses to this novel, flowable collagen-based hemostatic agent to the original flour formulation to confirm that the new method of delivery did not interfere with the hemostatic properties of the MCH flour. Results When observed visually, the flowable MCH flour mixed with saline (FL) provided more precise application and uniform coverage to injured tissues compared to the dry MCH flour alone (F0). All of the treatments (FL, F0, and gauze) exhibited comparable Lewis bleed grade at all three time points evaluated in the capsular resection liver injury model (bleed grade: 1.0-1.3; p> 0.05 in all cases). FL and F0 exhibited comparable 100% acute hemostatic efficacy and similar long-term histomorphological properties (up to 120 days) in a capsular resection liver injury in pigs, while gauze resulted in significantly lower rates of acute hemostatic efficacy (8-42%, p<0.05 in all cases). In an ovine model of dorsal laminectomy and durotomy, FL and F0 again exhibited comparable results without any neurological effects. Conclusion Flowable microfibrillar collagen was shown to yield favorable short- and long-term outcomes in two representative applications where hemostatic efficacy is critical to surgical success.
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Affiliation(s)
- Spencer P Lake
- Department of Mechanical Engineering & Materials Science, Washington University in St. Louis, St. Louis, MO, USA
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Wang H, Cheng J, Sun F, Dou X, Liu J, Wang Y, Li M, Gao J, Liu X, Wang X, Yang F, Zhu Z, Shen H, Zhang L, Tang P, Wu D. A Super Tough, Rapidly Biodegradable, Ultrafast Hemostatic Bioglue. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023; 35:e2208622. [PMID: 36579739 DOI: 10.1002/adma.202208622] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/24/2022] [Indexed: 06/17/2023]
Abstract
Death happening due to massive hemorrhage has been involved in military conflicts, traffic accidents, and surgical injuries of various human disasters. Achieving rapid and effective hemostasis to save lives is crucial in urgent massive bleeding situations. Herein, a covalent cross-linked AG-PEG glue based on extracellular matrix-like amino-gelatin (AG) and PEG derivatives is developed. The AG-PEG glue gelatinizes fast and exhibits firm and indiscriminate close adhesion with various moist tissues upon being dosed. The formed glue establishes an adhesive and robust barrier to seal the arterial, hepatic, and cardiac hemorrhagic wounds, enabling it to withstand up to 380 mmHg blood pressure in comparison with normal systolic blood pressure of 60-180 mmHg. Remarkably, massive bleeding from a pig cardiac penetrating hole with 6 mm diameter is effectively stopped using the glue within 60 s. Postoperative indexes of the treated pig gradually recover and the cardiac wounds regrow significantly at 14 days. Possessing on-demand solubility, self-gelling, and rapid degradability, the AG-PEG glue may provide a fascinating stop-bleeding approach for clinical hemostasis and emergency rescue.
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Affiliation(s)
- Hufei Wang
- Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China
- School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Junyao Cheng
- Senior Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China
| | - Feifei Sun
- CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China
| | - Xueyu Dou
- Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China
| | - Jianheng Liu
- Senior Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China
| | - Yiru Wang
- Department of Ultrasound, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China
| | - Ming Li
- Senior Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China
| | - Jianpeng Gao
- Senior Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China
| | - Xiao Liu
- Senior Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China
| | - Xing Wang
- Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China
- School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Fei Yang
- Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China
- School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Ziran Zhu
- Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China
- School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Hong Shen
- Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China
- School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Licheng Zhang
- Senior Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China
| | - Peifu Tang
- Senior Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Beijing, 100853, China
| | - Decheng Wu
- Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry Chinese Academy of Sciences, Beijing, 100190, China
- Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, China
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6
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Li XF, Lu P, Jia HR, Li G, Zhu B, Wang X, Wu FG. Emerging materials for hemostasis. Coord Chem Rev 2023. [DOI: 10.1016/j.ccr.2022.214823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Dhandapani V, Ringuette V, Desrochers M, Sirois M, Vermette P. Composition, host responses and clinical applications of bioadhesives. J Biomed Mater Res B Appl Biomater 2022; 110:2779-2797. [PMID: 35748414 DOI: 10.1002/jbm.b.35113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 05/08/2022] [Accepted: 06/08/2022] [Indexed: 12/15/2022]
Abstract
Bioadhesives are medical devices used to join or seal tissues that have been injured or incised. They have been classified into tissue adhesives, sealants, and hemostatic agents. Bioadhesives such as FloSeal®, CoSeal®, BioGlue®, Evicel®, Tisseel®, Progel™ PALS, and TissuGlu® have been commercialized and used in clinical setting. They can be formulated with natural or synthetic components or a combination of both including albumin, glutaraldehyde, chitosan, cyanoacrylate, fibrin and thrombin, gelatin, polyethylene glycol (PEG), along with urethanes. Each formulation has intrinsic properties and has been developed and validated for a specific application. This review article briefs the mechanisms by which bioadhesives forms adhesion to tissues and highlights the correlation between bioadhesives composition and their potential host responses. Furthermore, clinical applications of bioadhesives and their application-driven requirements are outlined.
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Affiliation(s)
- Vignesh Dhandapani
- Department of Chemical and Biotechnological Engineering, Laboratoire de bio-ingénierie et de biophysique de l'Université de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec, Canada.,Faculté de médecine et des sciences de la santé, Centre de Recherche du CHUS, Sherbrooke, Québec, Canada
| | - Vickie Ringuette
- Department of Surgery, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada
| | - Monika Desrochers
- Department of Chemical and Biotechnological Engineering, Laboratoire de bio-ingénierie et de biophysique de l'Université de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec, Canada
| | - Marco Sirois
- Faculté de médecine et des sciences de la santé, Centre de Recherche du CHUS, Sherbrooke, Québec, Canada.,Department of Surgery, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec, Canada
| | - Patrick Vermette
- Department of Chemical and Biotechnological Engineering, Laboratoire de bio-ingénierie et de biophysique de l'Université de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec, Canada.,Faculté de médecine et des sciences de la santé, Centre de Recherche du CHUS, Sherbrooke, Québec, Canada
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Gelatin-based hemostatic agents for medical and dental application at a glance: A narrative literature review. Saudi Dent J 2022; 34:699-707. [PMID: 36570577 PMCID: PMC9767835 DOI: 10.1016/j.sdentj.2022.11.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 11/07/2022] [Accepted: 11/09/2022] [Indexed: 11/17/2022] Open
Abstract
Uncontrolled bleeding is linked to higher treatment costs, risk of post-surgical infection and increased disease and death. Hemostatic agents are used to treat excessive bleeding. A good hemostatic agent controls bleeding effectively, reduces the need for blood transfusion, removes the need for systemic drugs to control bleeding, results in shorter surgery time, and reduces the cost and length of hospital stay of the patient. Gelatin-based hemostatic agents have been widely used in medical and dental procedures, owing to their biodegradability and biocompatibility, as well as availability and low cost of raw materials. In this narrative literature review, we discuss the background and different types of gelatin-based hemostatic agents in medical and dental procedures, the comparison of gelatin-based and non-gelatin-based hemostatic agents, and the usage and development of enhanced or novel gelatin-based hemostatic agents. Gelatin-based hemostatic agents are effective and important part of bleeding control, as evidenced by its wide application in medicine and dentistry. The development of novel combination gelatin-based hemostatic agents has much potential for effective control of excessive bleeding.
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Shu H, Xia Z, Qin X, Wang X, Lu W, Luo Q, Zhang Z, Xiong X. The clinical efficacy of collagen dressing on chronic wounds: A meta-analysis of 11 randomized controlled trials. Front Surg 2022; 9:978407. [PMID: 36117827 PMCID: PMC9473315 DOI: 10.3389/fsurg.2022.978407] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 08/10/2022] [Indexed: 11/13/2022] Open
Abstract
Objective This study aims to evaluate the clinical efficacy of collagen dressing for patients with chronic wounds. Materials and methods Relevant randomized controlled trials were searched from the databases such as PubMed, EMBASE, and the Cochrane library as of January 2022. For dichotomous outcomes and continuous outcomes, risk ratio and mean difference were calculated, respectively. Subgroup analysis was performed according to the type of chronic ulcer and follow-up. In addition, trial sequential analysis (TSA) was performed to further verify the results. Jadad score was used to assess the quality of trials. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was utilized to assess the level of evidence for outcomes. Results In 11 studies, a total of 961 patients of whom 485 were in the collagen group. Compared with standard of care (SOC) alone, the group that added an extra collagen dressing achieved a higher wound healing rate (Risk Ratio = 1.53; 95% CI, 1.33–1.77). The collagen group also showed a higher healing velocity than the SOC group (Mean Difference, 2.69; 95% CI, 0.87–4.51). In addition, the adverse events related to dressing between the two groups were similar (Risk Ratio = 0.67; 95% CI, 0.44–1.01). Conclusion Collagen dressing increases the wound healing rate and may be an effective and safe treatment for chronic wound management. However, more extensive research shall be conducted to substantiate these results. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=245728, identifier: CRD42021245728.
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Affiliation(s)
- Hongxin Shu
- Department of Vascular Surgery, The First Hospital of Nanchang, Nanchang, China
- Second Clinical Medical College, Nanchang University Medical School, Nanchang, China
| | - Zhiyu Xia
- Second Clinical Medical College, Nanchang University Medical School, Nanchang, China
| | - Xuan Qin
- Department of Vascular Surgery, The First Hospital of Nanchang, Nanchang, China
| | - Xiaowei Wang
- Second Clinical Medical College, Nanchang University Medical School, Nanchang, China
| | - Weihang Lu
- Vascular and Endovascular Surgery, the PLA General Hospital, Beijing, China
| | - Qingyu Luo
- Department of Vascular Surgery, The First Hospital of Nanchang, Nanchang, China
| | - Zhenxiong Zhang
- Department of Vascular Surgery, The First Hospital of Nanchang, Nanchang, China
| | - Xiaowei Xiong
- Department of Vascular Surgery, The First Hospital of Nanchang, Nanchang, China
- Correspondence: Xiaowei Xiong
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Li C, Duan W, Zhu Y, Li G, Gao M, Weng Z, Zhu Y, Bu Y. Cohesion Design-Led Tough Sealants with Controllably Dissolvable Properties. ACS APPLIED MATERIALS & INTERFACES 2022; 14:34415-34426. [PMID: 35857427 DOI: 10.1021/acsami.2c08328] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Leakage is a common complication of surgeries and injuries, causing pain and increasing the economic burden on patients. Although there are commercially available sealants for leakage prevention, few of them are entirely satisfactory due to disease transmission, high cost, and poor biocompatibility. In addition, none of them can be controllably removed for further healthcare. In this paper, by using cohesion design, a sealant based on amino-modified gelatin (AG) and bi-polyethylene glycol N-hydroxysuccinimide active ester (Bi-PEG-SS) was fabricated. To increase the bursting pressure, the cohesion strength was enhanced by increasing the cross-linking density of the sealant. To endow the sealant with controllably dissolvable properties, the smart succinic ester units were introduced into the cohesion network. Both the in vitro and in vivo experiments showed that this sealant processed high bursting pressure with efficient hemorrhage control. Moreover, no side effects were observed after 7 days of in vivo sealing, including little inflammation and fibrogenesis. These results, together with the easy availability of the raw materials, revealed that this sealant might be a promising alternative for leakage sealing.
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Affiliation(s)
- Chaowei Li
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Wanglin Duan
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Ye Zhu
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Guanying Li
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an 710061, China
| | - Min Gao
- Institute of Molecular and Translational Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an 710061, China
| | - Zuquan Weng
- College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China
| | - Yuan Zhu
- Department of Gynecology, The Affiliated Maternal and Child Healthcare Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
- Department of Gynecology, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, China
| | - Yazhong Bu
- Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
- Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an 710061, China
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11
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Park YM, Seo HI, Kim JH, Yoon SP, Lee H, Lee MS. Clinical application of a new hemostatic material using mussel-inspired catecholamine hemostat: A pilot study. Ann Hepatobiliary Pancreat Surg 2021; 26:98-103. [PMID: 34840145 PMCID: PMC8901974 DOI: 10.14701/ahbps.21-077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/02/2021] [Accepted: 08/16/2021] [Indexed: 12/02/2022] Open
Abstract
Backgrounds/Aims This study aimed to evaluate clinical application of InnoSEAL Plus (a mussel-inspired catecholamine hemostat) as a new hemostatic material for humans. Methods Patients treated with topical hemostatic patches after liver resection were enrolled. They were divided into an experimental group (InnoSEAL Plus group) and two control groups (TachoSil® group and Surgicel Fibrillar® group) for efficacy evaluation. Results A total of 15 patients were enrolled. Each group had five patients. The 3-minute hemostasis success rate was 80.0% (4/5 patients) in the InnoSEAL Plus group, 80.0% (4/5 patients) in the TachoSil® group, and 40.0% (2/5 patients) in the Surgicel Fibrillar® group, showing no significant difference in the success rate among these groups (p > 0.05). All three groups exhibited 100% success rate for 10-minute hemostasis. Both InnoSEAL Plus and TachoSil® groups had one patient developing adverse events, which were treated easily with drug administrations. Conclusions InnoSEAL Plus is expected to be functionally not inferior to other conventional hemostatic agents. However, it is necessary to confirm this through multicenter prospective studies in the future.
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Affiliation(s)
- Young-Mok Park
- Department of Surgery, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Hyung-Il Seo
- Department of Surgery, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Jae-Hoon Kim
- Department of Trauma Surgery and Surgical Critical Care, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Sung Pil Yoon
- Department of Surgery, Gang-an Hospital, Busan, Korea
| | - Haeshin Lee
- Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea
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12
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MacDonald MH, Zhang G, Tasse L, Wang D, De Leon H, Kocharian R. Hemostatic efficacy of two topical adjunctive hemostats in a porcine spleen biopsy punch model of moderate bleeding. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2021; 32:127. [PMID: 34591193 PMCID: PMC8484166 DOI: 10.1007/s10856-021-06586-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 08/12/2021] [Indexed: 05/19/2023]
Abstract
Topical hemostatic agents have become essential tools to aid in preventing excessive bleeding in surgical or emergency settings and to mitigate the associated risks of serious complications. In the present study, we compared the hemostatic efficacy of SURGIFLO® Hemostatic Matrix Kit with Thrombin (Surgiflo-flowable gelatin matrix plus human thrombin) to HEMOBLAST™ Bellows Hemostatic Agent (Hemoblast-a combination product consisting of collagen, chondroitin sulfate, and human thrombin). Surgiflo and Hemoblast were randomly tested in experimentally induced bleeding lesions on the spleens of four pigs. Primary endpoints included hemostatic efficacy measured by absolute time to hemostasis (TTH) within 5 min. Secondary endpoints included the number of product applications and the percent of product needed from each device to achieve hemostasis. Surgiflo demonstrated significantly higher hemostatic efficacy and lower TTH (p < 0.01) than Hemoblast. Surgiflo-treated lesion sites achieved hemostasis in 77.4% of cases following a single product application vs. 3.3% of Hemoblast-treated sites. On average, Surgiflo-treated sites required 63% less product applications than Hemoblast-treated sites (1.26 ± 0.0.51 vs. 3.37 ± 1.16). Surgiflo provided more effective and faster hemostasis than Hemoblast. Since both products contain thrombin to activate endogenous fibrinogen and accelerate clot formation, the superior hemostatic efficacy of Surgiflo in the porcine spleen punch biopsy model seems to be due to Surgiflo's property as a malleable barrier able to adjust to defect topography and to provide an environment for platelets to adhere and aggregate. Surgiflo combines a flowable gelatin matrix and a delivery system well-suited for precise application to bleeding sites where other methods of hemostasis may be impractical or ineffective.
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Affiliation(s)
- Melinda H MacDonald
- Ethicon, Inc., Johnson & Johnson, US Highway 22 West, Somerville, NJ, 08876-0151, USA
| | - Gary Zhang
- Ethicon, Inc., Johnson & Johnson, US Highway 22 West, Somerville, NJ, 08876-0151, USA
| | - Laura Tasse
- NAMSA, 6750 Wales Rd, Northwood, OH, 43619, USA
| | - Daidong Wang
- Cardiovascular and Specialty Solutions (CSS), Johnson & Johnson, 29A Technology Dr, Irvine, CA, 92618, USA
| | - Hector De Leon
- Scientific Consultant, 184 Bonita Hills Rd, Athens, GA, 30605, USA.
| | - Richard Kocharian
- Ethicon, Inc., Johnson & Johnson, US Highway 22 West, Somerville, NJ, 08876-0151, USA
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13
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Chen S, Gil CJ, Ning L, Jin L, Perez L, Kabboul G, Tomov ML, Serpooshan V. Adhesive Tissue Engineered Scaffolds: Mechanisms and Applications. Front Bioeng Biotechnol 2021; 9:683079. [PMID: 34354985 PMCID: PMC8329531 DOI: 10.3389/fbioe.2021.683079] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 06/15/2021] [Indexed: 11/13/2022] Open
Abstract
A variety of suture and bioglue techniques are conventionally used to secure engineered scaffold systems onto the target tissues. These techniques, however, confront several obstacles including secondary damages, cytotoxicity, insufficient adhesion strength, improper degradation rate, and possible allergic reactions. Adhesive tissue engineering scaffolds (ATESs) can circumvent these limitations by introducing their intrinsic tissue adhesion ability. This article highlights the significance of ATESs, reviews their key characteristics and requirements, and explores various mechanisms of action to secure the scaffold onto the tissue. We discuss the current applications of advanced ATES products in various fields of tissue engineering, together with some of the key challenges for each specific field. Strategies for qualitative and quantitative assessment of adhesive properties of scaffolds are presented. Furthermore, we highlight the future prospective in the development of advanced ATES systems for regenerative medicine therapies.
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Affiliation(s)
- Shuai Chen
- Department of Biomedical Engineering, Emory University School of Medicine, Georgia Institute of Technology, Atlanta, GA, United States
| | - Carmen J. Gil
- Department of Biomedical Engineering, Emory University School of Medicine, Georgia Institute of Technology, Atlanta, GA, United States
| | - Liqun Ning
- Department of Biomedical Engineering, Emory University School of Medicine, Georgia Institute of Technology, Atlanta, GA, United States
| | - Linqi Jin
- Department of Biomedical Engineering, Emory University School of Medicine, Georgia Institute of Technology, Atlanta, GA, United States
| | - Lilanni Perez
- Department of Biomedical Engineering, Emory University School of Medicine, Georgia Institute of Technology, Atlanta, GA, United States
| | - Gabriella Kabboul
- Department of Biomedical Engineering, Emory University School of Medicine, Georgia Institute of Technology, Atlanta, GA, United States
| | - Martin L. Tomov
- Department of Biomedical Engineering, Emory University School of Medicine, Georgia Institute of Technology, Atlanta, GA, United States
| | - Vahid Serpooshan
- Department of Biomedical Engineering, Emory University School of Medicine, Georgia Institute of Technology, Atlanta, GA, United States
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States
- Children’s Healthcare of Atlanta, Atlanta, GA, United States
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14
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Bruckner BA, Spotnitz WD, Suarez E, Loebe M, Ngo U, Gillen DL, Manson RJ. Evaluation of the Safety and Efficacy of a Novel Thrombin Containing Combination Hemostatic Powder Using a Historical Control. Clin Appl Thromb Hemost 2021; 27:10760296211017238. [PMID: 34024165 PMCID: PMC8150456 DOI: 10.1177/10760296211017238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
This clinical study compares 2 hemostatic agents, a novel combination powder (CP) (HEMOBLAST™ Bellows) and an established polysaccharide starch powder (PP) (Arista™ AH) to assess the usefulness of CP. Retrospective comparative analysis of CP (July 2018 to July 2019, 68 patients) to PP (January 2011 to January 2013, 94 patients) in cardiothoracic patients was performed using linear regression models adjusting for age, sex, and procedure type for the endpoints: blood loss; protamine to skin closure time (hemostasis time); chest tube output and blood products required 48 hours postoperatively; ICU stay; postoperative comorbidities; and 30 day mortality. 162 patients (108 M: 54 F) underwent 162 cardiothoracic surgical procedures including: transplantation (n = 44), placement of ventricular assist device (n = 87), and others (n = 31). Use of CP compared to PP (Estimated Mean Difference [95% CI], P-value) produced significant reductions: blood loss (mL) (-886.51 [-1457.76, -312.26], P = 0.003); protamine to skin closure time (min) (-16.81 [-28.03, -5.59], P = 0.004); chest tube output (48 hrs, mL) (-445.76 [-669.38, -222.14], P < 0.001); packed red blood cell transfusions (units) (-0.98 [-1.56, -0.4], P = 0.001); and postoperative comorbidities (-0.31 [-0.55, -0.07], P = 0.012). There were no differences in the ICU stay (4.07 [-2.01, 10.15], P = 0.188) or 30-day mortality (0.57 [0.20, 1.63], P = 0.291). The use of CP in complex cardiothoracic operations resulted in improved hemostasis and significant clinical benefits in blood loss, transfusion requirements, morbidity, and time in operating room.
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Affiliation(s)
- Brian A Bruckner
- Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, TX, USA
| | - William D Spotnitz
- Department of Surgery, University of Virginia, Charlottesville, VA, USA.,Department of Medical Affairs, Biom'Up France SAS, Lyon, France
| | - Erik Suarez
- Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, TX, USA
| | - Matthias Loebe
- Miami Transplant Institute, University of Miami Health System, Miami, FL, USA
| | - Uy Ngo
- Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, TX, USA
| | - Daniel L Gillen
- Department of Statistics, University of California at Irvine, Irvine, CA, USA.,Department of Epidemiology, University of California at Irvine, Irvine, CA, USA
| | - Roberto J Manson
- Department of Medical Affairs, Biom'Up France SAS, Lyon, France.,Department of Surgery, Duke University, Durham, NC, USA.,Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA
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15
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Kim K, Ryu JH, Koh MY, Yun SP, Kim S, Park JP, Jung CW, Lee MS, Seo HI, Kim JH, Lee H. Coagulopathy-independent, bioinspired hemostatic materials: A full research story from preclinical models to a human clinical trial. SCIENCE ADVANCES 2021; 7:7/13/eabc9992. [PMID: 33762330 PMCID: PMC7990328 DOI: 10.1126/sciadv.abc9992] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 02/05/2021] [Indexed: 05/05/2023]
Abstract
Since the first report of underwater adhesive proteins of marine mussels in 1981, numerous studies have reported mussel-inspired synthetic adhesive polymers. However, none of them have developed up to human-level translational studies. Here, we report a sticky polysaccharide that effectively promotes hemostasis from animal bleeding models to first-in-human hepatectomy. We found that the hemostatic material instantly generates a barrier layer that seals hemorrhaging sites. The barrier is created within a few seconds by in situ interactions with abundant plasma proteins. Therefore, as long as patient blood contains proper levels of plasma proteins, hemostasis should always occur even in coagulopathic conditions. To date, insufficient tools have been developed to arrest coagulopathic bleedings originated from genetic disorders, chronic diseases, or surgical settings such as organ transplantations. Mussel-inspired adhesion chemistry described here provides a useful alternative to the use of fibrin glues up to a human-level biomedical application.
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Affiliation(s)
- Keumyeon Kim
- Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
- R&D Center, InnoTherapy Inc., Seoul, Republic of Korea
| | - Ji Hyun Ryu
- Department of Carbon Convergence Engineering, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
| | - Mi-Young Koh
- R&D Center, InnoTherapy Inc., Seoul, Republic of Korea
| | - Sung Pil Yun
- Department of Surgery, Pusan National University Hospital, Busan, Republic of Korea
| | - Soomi Kim
- R&D Center, InnoTherapy Inc., Seoul, Republic of Korea
| | - Joseph P Park
- Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
| | - Chul-Woo Jung
- Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Moon Sue Lee
- R&D Center, InnoTherapy Inc., Seoul, Republic of Korea
| | - Hyung-Il Seo
- Department of Surgery, Pusan National University Hospital, Busan, Republic of Korea.
| | - Jae Hun Kim
- Department of Surgery, Pusan National University Hospital, Busan, Republic of Korea.
| | - Haeshin Lee
- Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
- R&D Center, InnoTherapy Inc., Seoul, Republic of Korea
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16
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Paternò VA, Bisin A, Addis A. Comparison of the efficacy of five standard topical hemostats: a study in porcine liver and spleen models of surgical bleeding. BMC Surg 2020; 20:215. [PMID: 32977788 PMCID: PMC7519517 DOI: 10.1186/s12893-020-00874-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 09/20/2020] [Indexed: 11/19/2022] Open
Abstract
Background Several topical hemostats are available to help control surgical bleeding. Cutanplast is a highly absorbent and porous gelatin product that is available in Fast sponge and powder forms. This study investigated the hemostatic efficacy of Cutanplast Standard and Fast gelatin sponge and powder and Emosist oxidized regenerated cellulose (ORC) gauze in porcine liver and spleen surgical bleeding models. Methods Cutanplast Standard and Fast gelatin sponge and Emosist ORC gauze were tested in liver abrasion/incision, liver puncture and spleen incision/puncture injuries, and Cutanplast Standard and Fast gelatin powder products were tested in liver abrasion/incision injuries. There were 13 liver injury (five abrasion, five incision and three puncture) and six spleen injury (three puncture and three incision sites) sites per animal. Results Rapid hemostasis (≤ 2–5 min) was achieved in the liver abrasion and incision models with all Cutanplast gelatin sponge and powder products and Emosist ORC gauze, except in the liver incision model, time to hemostasis was > 5 min with Cutanplast Standard gelatin powder and Emosist ORC gauze. Rapid hemostasis occurred with Cutanplast Fast gelatin sponge and Emosist ORC gauze in the liver puncture and spleen puncture and incision models. In the spleen incision model, Cutanplast Standard gelatin sponge had a time to hemostasis approaching 10 min. Conclusion Cutanplast gelatin sponge and powder products and Emosist ORC gauze may be suitable for surgical applications involving parenchymal organ bleeding, but certain products may perform better than others, including Cutanplast gelatin powder in diffuse mild bleeding (such as liver abrasion), and Cutanplast Fast gelatin sponge and Emosist ORC gauze for splenic bleeding.
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17
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MacDonald MH, Tasse L, Wang D, Zhang G, De Leon H, Kocharian R. Evaluation of the Hemostatic Efficacy of Two Powdered Topical Absorbable Hemostats Using a Porcine Liver Abrasion Model of Mild to Moderate Bleeding. J INVEST SURG 2020; 34:1198-1206. [PMID: 32928005 DOI: 10.1080/08941939.2020.1792007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Topical hemostatic agents, used alone or in combination, have become common adjuncts to manage tissue and organ bleeding resulting from trauma and surgical procedures. Oxidized regenerated cellulose (ORC) is one of the most commonly used adjunctive hemostatic agents. The aim of the present study was to compare the hemostatic efficacy of a novel ORC-based product, SURGICEL® Powder Absorbable Hemostat (Surgicel-P) to that of HEMOBLAST™ Bellows (Hemoblast-B), a collagen-based combination powder. METHODS Using an established porcine liver abrasion model, we randomly tested Surgicel-P and Hemoblast-B in 60 experimental lesion sites (30 per product tested). Primary endpoints included hemostatic efficacy measured by absolute time to hemostasis (TTH) within 5 minutes. We also examined number of applications required to achieve hemostasis, and sustained hemostasis following saline irrigation of test sites that achieved hemostasis. RESULTS Surgicel-P demonstrated significantly higher hemostatic efficacy and lower TTH (p < 0.01) than Hemoblast-B. Surgicel-P-treated lesion sites achieved hemostasis in 73.3% of cases following one product application vs. 3.3% of Hemoblast-B-treated sites. Of all sites that were assessed, hemostasis was achieved and sustained following irrigation at 93.3% of Surgicel-P-treated sites vs. 50.0% of Hemoblast-B-treated sites. The average number of Surgicel-P applications per site was 51% lower than the average number of applications used for Hemoblast-B. CONCLUSION Surgicel-P provided more effective and sustained hemostasis and faster TTH than Hemoblast-B. Surgicel-P represents a novel clinical alternative to provide adjunctive control of diffuse mild and moderate bleeding. Surgicel-P combines an ORC powder formulation and a delivery system in a device that is particularly useful for application on large surfaces and difficult-to-access anatomical locations where application of other forms of topical hemostats may be impractical.
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Affiliation(s)
| | | | - Daidong Wang
- Cardiovascular and Specialty Solutions (CSS), Irvine, California, USA
| | - Gary Zhang
- Ethicon, Inc, Johnson & Johnson, Somerville, New Jersey, USA
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18
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Almeida AC, Vale AC, Reis RL, Alves NM. Bioactive and adhesive properties of multilayered coatings based on catechol-functionalized chitosan/hyaluronic acid and bioactive glass nanoparticles. Int J Biol Macromol 2020; 157:119-134. [DOI: 10.1016/j.ijbiomac.2020.04.095] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 04/07/2020] [Accepted: 04/13/2020] [Indexed: 02/09/2023]
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19
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Pallaske F, Seebauer C, Kaltofen D, Dziomber S, Rudolph H, Schwanebeck U, Grählert X, Schulze G, Pallaske A, Boese-Landgraf J, Schlömann M, Daeschlein G. Results of a randomised controlled trial between an ORC collagen hemostatic agent and a carrier-bound fibrin sealant. J Visc Surg 2020; 158:11-18. [PMID: 32747306 DOI: 10.1016/j.jviscsurg.2020.06.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Despite ongoing optimisation of surgical techniques, hemostasis continues to be a fundamental challenge in many operations today. This randomised controlled trial compared the efficacy of a new hemostatic agent made of oxidised regenerated cellulose and collagen (ORC-Coll) with that of a conventional carrier-bound fibrin sealant (CBFS). METHODS Hemostasis was investigated representatively in the case of post-thyroidectomy bleeding from the resection surface. To demonstrate that ORC-Coll (mediCipio® A) has at least the same hemostatic efficacy as CBFS (Tachosil®), the volume of drainage fluid at the time of drain removal was used as the primary endpoint in a non-inferiority test with a significance level of 5%. The secondary endpoints included number and size of hemostatic agents required, adhesion of the hemostatic agent to the bleeding surface, intraoperative hemostatic effect, duration of drainage and adverse events during a six-month follow-up period. RESULTS A total of 150 patients (ORC-Coll: 75; CBFS: 75) were included. After operation, total volume of drainage fluid was 68.20±44.56mL in the ORC group and 68.21±40.20mL in the CBFS group. The non-inferiority of ORC-Coll compared to CBFS with regard to hemostatic efficacy was shown at a significance level of 5%. The results demonstrated effectiveness in achieving hemostasis without adverse events. CONCLUSIONS ORC-Coll is an effective hemostatic agent and barrier sealant without blood components, which ensures reliable prevention of intra- and postoperative bleeding. With use of the new technique, any risks associated with the use of human blood components are a priori eliminated.
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Affiliation(s)
- F Pallaske
- Medichema GmbH, Weststraße 57, 09112 Chemnitz, Germany.
| | - C Seebauer
- Department of Oral and Maxillofacial Surgery/Plastic Surgery, University Medicine Greifswald, Walther-Rathenau Str. 42a, 17475 Greifswald, Germany.
| | - D Kaltofen
- General and Visceral Surgery, Klinikum Chemnitz gGmbH, Flemmingstraße 2, 09116 Chemnitz, Germany.
| | - S Dziomber
- General and Visceral Surgery, Klinikum Chemnitz gGmbH, Flemmingstraße 2, 09116 Chemnitz, Germany.
| | - H Rudolph
- General and Visceral Surgery, Klinikum Chemnitz gGmbH, Flemmingstraße 2, 09116 Chemnitz, Germany.
| | - U Schwanebeck
- Carl-Gustav-Carus Faculty of Medicine, Technische Universität Dresden, Coordinating Centre for Clinical Trials Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
| | - X Grählert
- Carl-Gustav-Carus Faculty of Medicine, Technische Universität Dresden, Coordinating Centre for Clinical Trials Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
| | - G Schulze
- Carl-Gustav-Carus Faculty of Medicine, Technische Universität Dresden, Coordinating Centre for Clinical Trials Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
| | - A Pallaske
- Kreiskrankenhaus Stollberg gGmbH, Hospital of Internal Medicine II, Jahnsdorfer Straße 7, 09366 Stollberg, Germany.
| | - J Boese-Landgraf
- General and Visceral Surgery, Klinikum Chemnitz gGmbH, Flemmingstraße 2, 09116 Chemnitz, Germany.
| | - M Schlömann
- Technische Universität Bergakademie Freiberg, Institute of Biosciences, 09599 Freiberg, Germany.
| | - G Daeschlein
- Department of Oral and Maxillofacial Surgery/Plastic Surgery, University Medicine Greifswald, Walther-Rathenau Str. 42a, 17475 Greifswald, Germany.
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20
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Kim MH, Lee JN, Lee J, Lee H, Park WH. Enzymatically Cross-Linked Poly(γ-glutamic acid) Hydrogel with Enhanced Tissue Adhesive Property. ACS Biomater Sci Eng 2020; 6:3103-3113. [DOI: 10.1021/acsbiomaterials.0c00411] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
- Min Hee Kim
- Department of Organic Materials Engineering, Chungnam National University, Daejeon 34134, South Korea
| | - Jee Na Lee
- Department of Organic Materials Engineering, Chungnam National University, Daejeon 34134, South Korea
| | - Jeehee Lee
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34134, South Korea
| | - Haeshin Lee
- Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon 34134, South Korea
| | - Won Ho Park
- Department of Organic Materials Engineering, Chungnam National University, Daejeon 34134, South Korea
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21
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Gillman N, Lloyd D, Bindra R, Ruan R, Zheng M. Surgical applications of intracorporal tissue adhesive agents: current evidence and future development. Expert Rev Med Devices 2020; 17:443-460. [PMID: 32176853 DOI: 10.1080/17434440.2020.1743682] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Introduction: Traditional mechanical closure techniques pose many challenges including the risk of infection, tissue reaction, and injury to both patients and clinicians. There is an urgent need to develop tissue adhesive agents to reform closure technique. This review examined a variety of tissue adhesive agents available in the market in an attempt to gain a better understanding of intracorporal tissue adhesive agents as medical devices.Areas covered: Fundamental principles and clinical determinants of the tissue adhesives were summarized. The available tissue adhesives for intracorporal use and their relevant clinical evidence were then presented. Lastly, the perspective of future development for intracorporal tissue adhesive were discussed. Clinical evidence shows current agents are efficacious as adjunctive measures to mechanical closure and these agents have been trialed outside of clinical indications with varied results.Expert opinion: Despite some advancements in the development of tissue adhesives, there is still a demand to develop novel technologies in order to address unmet clinical needs, including low tensile strength in wet conditions, non-controllable polimerization and sub-optimal biocompatibility. Research trends focus on producing novel adhesive agents to remit these challenges. Examples include the development of biomimetic adhesives, externally activated adhesives, and multiple crosslinking strategies. Economic feasibility and biosafety are limiting factors for clinical implementation.
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Affiliation(s)
- Nicholas Gillman
- School of Medicine, Griffith University School of Medicine, Gold Coast, QLD, Australia.,Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, University of Western Australia, Perth, WA, Australia
| | - David Lloyd
- Griffith Centre for Orthopaedic Research and Engineering, Menzies Health Institute, Gold Coast, QLD, Australia
| | - Randy Bindra
- School of Medicine, Griffith University School of Medicine, Gold Coast, QLD, Australia.,Department of Plastic and Reconstructive Surgery, Gold Coast University Hospital, Southport, QLD, Australia
| | - Rui Ruan
- Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, University of Western Australia, Perth, WA, Australia.,Griffith Centre for Orthopaedic Research and Engineering, Menzies Health Institute, Gold Coast, QLD, Australia
| | - Minghao Zheng
- Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, University of Western Australia, Perth, WA, Australia.,Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, 6009, Australia
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22
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Pallaske F, Pallaske A, Herklotz K, Boese-Landgraf J. The significance of collagen dressings in wound management: a review. J Wound Care 2019; 27:692-702. [PMID: 30332361 DOI: 10.12968/jowc.2018.27.10.692] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Clinical experience and research has improved our understanding of wound healing which, in turn, has enabled health professionals to aid wound healing and manufacturers to develop modern wound dressings. The significant role of collagen in wound healing has led to the development of numerous products on the basis of this biological material. The main focus of this review is to provide a critical appraisal of publications about collagen and acellular collagen dressings with a fleece-like or spongy structure. It is intended for clinicians and researchers, and aims to keep them up-to-date in the complex field of interactive, collagen-based wound dressings, including their manufacture, combination possibilities, mechanisms of action, performance in the promotion of wound healing and indications. Despite the small number of clinical studies, the importance of acellular collagen dressings with a fleece- or sponge-like structure is likely to increase in the future. As there is no ideal wound dressing, the knowledge attained is meant to support health professionals in selecting the right product, and pave the way for new applications and clinical studies.
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Affiliation(s)
- Frank Pallaske
- Developer of Wound Dressings; medichema GmbH, Weststraße 57, 09112 Chemnitz, DE
| | - Anett Pallaske
- Resident Physician; Hospital of Internal Medicine II of the Kreiskrankenhaus Stollberg gGmbH, Jahnsdorfer Straße 7, 09366 Stollberg, DE
| | - Kurt Herklotz
- Microscopy expert; Institute of Biosciences of the Technische Universität Bergakademie Freiberg, Leipziger Str. 29, 09599 Freiberg, DE
| | - Joachim Boese-Landgraf
- Prof. Dr. med., former Head of the Hospital of General and Visceral Surgery, Klinikum Chemnitz gGmbH, Flemmingstraße 2, 09116 Chemnitz, DE
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23
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Jain R, Wairkar S. Recent developments and clinical applications of surgical glues: An overview. Int J Biol Macromol 2019; 137:95-106. [DOI: 10.1016/j.ijbiomac.2019.06.208] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 06/21/2019] [Accepted: 06/26/2019] [Indexed: 01/10/2023]
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24
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Kim MJ, Kim JH, Kim JS, Choe JH. Evaluation of a Novel Collagen Hemostatic Matrix: Comparison of Two Hemostatic Matrices in a Rabbits Jejunal Artery Injury Model. J Surg Res 2019; 243:553-559. [PMID: 31382076 DOI: 10.1016/j.jss.2019.05.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 03/23/2019] [Accepted: 05/08/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND We evaluated the hemostatic efficacy and immunogenicity of CollaStat compared with FloSeal in a rabbit jejunal artery injury model. METHODS A total of 27 experimental rabbits were used in the study. For each hemostatic agent, an injury was created in one of the right angles of the jejunal arteries originating from the vascular arcs. Time to hemostasis was determined after applying manual compression to the wound for 30 s, which was repeated a maximum of three times in cases of persistent bleeding. On postoperative day 7, the concentration of serum antithrombin antibody was measured among agent-treated and nontreated control groups. RESULTS The mean time to hemostasis for CollaStat was significantly shorter than for FloSeal (64.0 ± 5.0 versus 84.0 ± 7.8 s; P = 0.040). There were no significant differences in rabbit serum mean anti-thrombin Ab concentration between CollaStat-treated, FloSeal -treated, and the control groups (8.43 ± 0.44 versus 8.18 ± 7.8 versus 9.58 ± 1.11 ng/mL; P = 0.065). CONCLUSIONS According to our study, CollaStat was more efficient in achieving hemostasis in a rabbit jejunal artery injury and exhibited nonsignificant immunogenicity compared with FloSeal. These findings suggest that CollaStat has acceptable hemostatic potential for controlling significant arterial bleeding.
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Affiliation(s)
- Min Jhi Kim
- Division of Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jung-Han Kim
- Division of Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jee Soo Kim
- Division of Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jun-Ho Choe
- Division of Endocrine Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
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Logun MT, Dowling MB, Raghavan SR, Wallace ML, Schmiedt C, Stice S, Karumbaiah L. Expanding Hydrophobically Modified Chitosan Foam for Internal Surgical Hemostasis: Safety Evaluation in a Murine Model. J Surg Res 2019; 239:269-277. [PMID: 30884383 DOI: 10.1016/j.jss.2019.01.060] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Revised: 12/19/2018] [Accepted: 01/25/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND A novel injectable expanding foam based on hydrophobically modified chitosan (HM-CS) was developed to improve hemostasis during surgeries. HM-CS is an amphiphilic derivative of the natural biopolymer chitosan (CS); HM-CS has been shown to improve the natural hemostatic characteristics of CS, but its internal safety has not been systematically evaluated. The goal of this study was to compare the long-term in vivo safety of HM-CS relative to a commonly used fibrin sealant (FS), TISSEEL (Baxter). METHODS Sixty-four Sprague-Dawley rats (275-325 g obtained from Charles River Laboratories) were randomly assigned to control (n = 16) or experimental (n = 48) groups. Samples of the test materials (HM-CS [n = 16], CS [n = 16], and FS [n = 16]) applied to a nonlethal liver excision (0.4 ± 0.3 g of the medial lobe) in rats were left inside the abdomen to degrade. Animals were observed daily for signs of morbidity and mortality. Surviving animals were sacrificed at 1 and 6 wk; the explanted injury sites were microscopically assessed. RESULTS All animals (64/64) survived both the 1- and 6-wk time points without signs of morbidity. Histological examination showed a comparable pattern of degradation for the various test materials. FS remnants and significant adhesions to neighboring tissues were observed at 6 wk. Residual CS and HM-CS were observed at the 6 wk with fatty deposits at the site of injury. Minimal adhesions were observed for CS and HM-CS. CONCLUSIONS The internal safety observed in the HM-CS test group after abdominal implantation indicates that injectable HM-CS expanding foam may be an appropriate internal use hemostatic candidate.
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Affiliation(s)
- Meghan T Logun
- Regenerative Bioscience Center, University of Georgia, Athens, Georgia
| | | | - Srinivasa R Raghavan
- Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland
| | - Mandy L Wallace
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, Georgia
| | - Chad Schmiedt
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, Georgia
| | - Steven Stice
- Regenerative Bioscience Center, University of Georgia, Athens, Georgia
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Ardehali A, Spotnitz WD, Hoffman RW, Olson SA, Bochicchio GV, Hermann MC, Lakshman S, Dang NC, Centis V, Gillen DL, Schorn IJ, Spotnitz RH. Evaluation of the safety and efficacy of a new hemostatic powder using a quantitative surface bleeding severity scale. J Card Surg 2019; 34:50-62. [PMID: 30629770 DOI: 10.1111/jocs.13982] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
AIMS OF THE STUDY The safety and efficacy of a hemostatic powder (HP) versus a control agent, absorbable gelatin sponge and thrombin (G + T), were assessed, using a validated, quantitative bleeding severity scale. METHODS Subjects were randomized to receive HP (256 subjects) or G + T (132 subjects) for treatment of minimal, mild, or moderate bleeding at 20 investigational sites. The primary efficacy endpoint was non-inferiority of HP relative to G + T for success at achieving hemostasis within 6 minutes. Secondary endpoints in rank order included: superiority of HP relative to G + T in mean preparation time; non-inferiority of HP relative to G + T for achieving hemostasis within 3 min; superiority of HP relative to G + T for achieving hemostasis within 6 min; and superiority of HP relative to G + T for success for achieving hemostasis within 3 min. RESULTS A total of 388 subjects were included in the primary efficacy analysis. At 6 min, hemostasis was achieved in 93.0% (238/256) of the HP group compared to 77.3% (102/132) of the G + T group (non-inferiority P < 0.0001, superiority P < 0.0001). All secondary endpoints were met. Complications were comparable between treatment groups. CONCLUSIONS HP had superior rates of hemostasis, shorter preparation time, and a similar safety profile compared to G + T in this prospective, randomized trial using quantitative bleeding severity criteria.
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Affiliation(s)
- Abbas Ardehali
- Department of Surgery, University of California at Los Angeles, Los Angeles, California
| | - William D Spotnitz
- Department of Surgery, University of Virginia, Charlottesville, Virginia.,Department of Medical Affairs, Biom'up, Lyon, France
| | | | - Steven A Olson
- Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, North Carolina
| | - Grant V Bochicchio
- Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
| | - Mark C Hermann
- General Orthopedics and Surgery, Spectrum Medical, Danville, Virginia
| | - Shankar Lakshman
- Department of Surgery, Huntington Hospital, Pasadena, California
| | - Nick C Dang
- Department of Surgery, Queens Hospital, Honolulu, Hawaii
| | - Valerie Centis
- Department of Research and Development, Biom'up, Lyon, France
| | - Dan L Gillen
- Department of Statistics, Department of Epidemiology, University of California at Irvine, Irvine, California
| | - Ian J Schorn
- NAMSA, Clinical and Consulting, Minneapolis, Minnesota
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- Advanced Powder Investigators Group (APIG)
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Gleason S, Mehl D, Payne W, Parry S, Stein AB. Microporous polysaccharide hemosphere efficacy and safety in primary total knee arthroplasty. J Orthop 2019; 16:19-24. [PMID: 30765929 PMCID: PMC6355655 DOI: 10.1016/j.jor.2018.11.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Accepted: 11/28/2018] [Indexed: 11/23/2022] Open
Abstract
Absorbable hemostats such as microporous polysaccharide hemospheres (MPH) are used to manage hemostasis and prevent complications in total knee arthroplasty (TKA). We aimed to determine safety and effectiveness of MPH use in TKA. Records were reviewed for blood loss, hematomas, and infections. No differences existed regarding demographics, superficial infections (P = 0.933) or hematomas (P = 0.393). Positive correlation existed between hematoma and superficial infection (P = 0.009). Blood loss was greater in the treatment group (P = 0.014). MPH demonstrated inferior bleeding control and had no effect on complications. Our results suggest application of this agent may be unnecessary.
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Affiliation(s)
- Scott Gleason
- Midwestern University/Franciscan St. James Health, 20201 South Crawford Ave, Olympia Fields, IL, 60461, USA
| | - David Mehl
- Midwestern University/Franciscan St. James Health, 20201 South Crawford Ave, Olympia Fields, IL, 60461, USA
| | - William Payne
- Midwestern University/Franciscan St. James Health, 20201 South Crawford Ave, Olympia Fields, IL, 60461, USA
| | - Steve Parry
- Midwestern University/Franciscan St. James Health, 20201 South Crawford Ave, Olympia Fields, IL, 60461, USA
| | - Amy Buros Stein
- Midwestern University, 19555 North 59th Ave, Glendale, AZ, 85308, USA
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Sun H, Lv L, Bai Y, Yang H, Zhou H, Li C, Yang L. Nanotechnology-enabled materials for hemostatic and anti-infection treatments in orthopedic surgery. Int J Nanomedicine 2018; 13:8325-8338. [PMID: 30584303 PMCID: PMC6289228 DOI: 10.2147/ijn.s173063] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The hemostatic and anti-infection treatments in the field of orthopedics are always the pivotal yet challenging topics. In the first part of this review, synthesized or naturally derived nanoscale agents and materials for hemostatic treatment in orthopedic surgery are introduced. The hemostatic mechanisms and the safety concerns of these nanotechnology-enabled materials are discussed. Beside the materials to meet hemostatic needs in orthopedic surgery, the need for antimicrobial or anti-infection strategy in orthopedic surgery also becomes urgent. Nanosilver and its derivatives have the most consistent anti-infective effect and thus high translational potential for clinical applications. In the second part, the factors affecting the antimicrobial effect of nanosilver and its application status are summarized. Finally, the status and translational potential of various nanotechnology-enabled materials and agents for hemostatic and anti-infective treatments in orthopedic surgery are discussed.
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Affiliation(s)
- Haolin Sun
- Department of Orthopaedics, Peking University First Hospital, Beijing 100034, China,
- International Research Center for Translational Orthopaedics (IRCTO), Soochow University, Suzhou 215006, China,
| | - Lu Lv
- Orthopaedic Institute and Department of Orthopaedics, Soochow University, Suzhou 215006, China,
| | - Yanjie Bai
- School of Public Health, Medical College, Soochow University, Suzhou 215000, China
| | - Huilin Yang
- International Research Center for Translational Orthopaedics (IRCTO), Soochow University, Suzhou 215006, China,
- Orthopaedic Institute and Department of Orthopaedics, Soochow University, Suzhou 215006, China,
| | - Huan Zhou
- International Research Center for Translational Orthopaedics (IRCTO), Soochow University, Suzhou 215006, China,
- School of Mechanical Engineering, Jiangsu University of Technology, Changzhou 213001, China
| | - Chunde Li
- Department of Orthopaedics, Peking University First Hospital, Beijing 100034, China,
| | - Lei Yang
- International Research Center for Translational Orthopaedics (IRCTO), Soochow University, Suzhou 215006, China,
- Orthopaedic Institute and Department of Orthopaedics, Soochow University, Suzhou 215006, China,
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First Safety and Performance Evaluation of T45K, a Self-Assembling Peptide Barrier Hemostatic Device, After Skin Lesion Excision. Dermatol Surg 2018; 44:939-948. [PMID: 29381543 PMCID: PMC6039376 DOI: 10.1097/dss.0000000000001468] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND The self-assembling peptide barrier T45K (SAPB-T45K) is an oligopeptide that rapidly forms a biocompatible hemostatic barrier when applied to wounds. OBJECTIVE Evaluate safety and performance of SAPB-T45K in cutaneous surgery. MATERIALS AND METHODS In this single-blind study, after sequential shave excision of 2 lesions, wounds were randomized (intrapatient) to SAPB-T45K or control treatment. Safety was assessed at treatment, Day 7, and Day 30. Performance was evaluated using time to hemostasis (TTH) and ASEPSIS wound scores, with a subgroup analysis for patients with or without antiplatelet therapy. RESULTS Each of 46 patients (10 [22%] with antiplatelet therapy) received randomized SAPB-T45K or control treatment for 2 wounds. Safety assessments were similar, and ASEPSIS scores reflected normal healing in both wound groups. SAPB-T45K demonstrated significantly faster median TTH (24.5 [range, 7–165] seconds) compared with control (44 [10–387] seconds), for a 41% median TTH reduction (18 [95% confidence interval, 7–35] seconds, p < .001). SAPB-T45K provided an identical median TTH of 24 seconds, regardless of antiplatelet therapy. Control median TTH was 90 and 40 seconds for patients taking or not taking antiplatelet therapy, respectively. CONCLUSIONS SAPB-T45K provided significantly faster median TTH versus control, especially with antiplatelet therapy, and safety profiles were similar.
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Zhu W, Chuah YJ, Wang DA. Bioadhesives for internal medical applications: A review. Acta Biomater 2018; 74:1-16. [PMID: 29684627 DOI: 10.1016/j.actbio.2018.04.034] [Citation(s) in RCA: 120] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Revised: 03/08/2018] [Accepted: 04/19/2018] [Indexed: 12/17/2022]
Abstract
Bioadhesives such as tissue adhesives, hemostatic agents, and tissue sealants have gained increasing popularity in different areas of clinical operations during the last three decades. Bioadhesives can be categorized into internal and external ones according to their application conditions. External bioadhesives are generally applied in topical medications such as wound closure and epidermal grafting. Internal bioadhesives are mainly used in intracorporal conditions with direct contact to internal environment including tissues, organs and body fluids, such as chronic organ leak repair and bleeding complication reduction. This review focuses on internal bioadhesives that, in contrast with external bioadhesives, emphasize much more on biocompatibility and adhesive ability to wet surfaces rather than on gluing time and intensity. The crosslinking mechanisms of present internal bioadhesives can be generally classified as follows: 1) chemical conjugation between reactive groups; 2) free radical polymerization by light or redox initiation; 3) biological or biochemical coupling with specificity; and 4) biomimetic adhesion inspired from natural phenomena. In this review, bioadhesive products of each class are summarized and discussed by comparing their designs, features, and applications as well as their prospects for future development. STATEMENT OF SIGNIFICANCE Despite the emergence of numerous novel bioadhesive formulations in recent years, thus far, the classification of internal and external bioadhesives has not been well defined and universally acknowledged. Many of the formulations have been proposed for treatment of several diseases even though they are not applicable for such conditions. This is because of the lack of a systematic standard or evaluation protocol during the development of a new adhesive product. In this review, the definition of internal and external bioadhesives is given for the first time, and with a focus on internal bioadhesives, the criteria of an ideal internal bioadhesive are adequately discussed; this is followed by the review of recently developed internal bioadhesives based on different gluing mechanisms.
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Affiliation(s)
- Wenzhen Zhu
- Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637457, Singapore
| | - Yon Jin Chuah
- School of Materials Science and Engineering, Nanyang Technological University, Singapore 637335, Singapore
| | - Dong-An Wang
- Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637457, Singapore.
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Kim M, Ondrusek BA, Lee C, Douglas WG, Chung H. Synthesis of lightly crosslinked zwitterionic polymer-based bioinspired adhesives for intestinal tissue sealing. ACTA ACUST UNITED AC 2018. [DOI: 10.1002/pola.29041] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- Minkyu Kim
- Department of Chemical and Biomedical Engineering; Florida State University, 2525 Pottsdamer Street, Building A, Suite A131; Tallahassee Florida 32310
| | - Brian A. Ondrusek
- Department of Chemical and Biomedical Engineering; Florida State University, 2525 Pottsdamer Street, Building A, Suite A131; Tallahassee Florida 32310
| | - Choogon Lee
- Department of Biomedical Sciences; Florida State University; Tallahassee Florida 32306
| | - Wade G. Douglas
- General Surgery Residency Program at Tallahassee Memorial Healthcare, College of Medicine, Florida State University, 1401 Centerville Road, Suite 107; Tallahassee Florida 32308
| | - Hoyong Chung
- Department of Chemical and Biomedical Engineering; Florida State University, 2525 Pottsdamer Street, Building A, Suite A131; Tallahassee Florida 32310
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Srinivasan PK, Sperber V, Afify M, Tanaka H, Fukushima K, Kögel B, Gremse F, Tolba R. Novel synthetic adhesive as an effective alternative to Fibrin based adhesives. World J Hepatol 2017; 9:1030-1039. [PMID: 28932349 PMCID: PMC5583535 DOI: 10.4254/wjh.v9.i24.1030] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 06/06/2017] [Accepted: 07/10/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To compare a novel, fully synthetic, polyurethane based glue (MAR-1) to fibrin sealant in a partial liver resection rat model.
METHODS After 50% resection of the lateral left liver lobe in male Wistar rats (n = 7/group/time point), MAR-1, Fibrin or NaCl was applied. After 14, 21 and 90 postoperative days, sealant degradation, intra-abdominal adhesions were scored, and histological examination of liver tissue was performed.
RESULTS (Mean ± SEM) (MAR-1 vs Fibrin vs NaCl). Bleeding mass was significantly higher in NaCl (3.36 ± 0.51 g) compared to MAR-1 (1.44 ± 0.40 g) and Fibrin (1.16 ± 0.32 g). At 14 and 90 d, bleeding time was significantly lower in MAR-1 (6.00 ± 0.9 s; 13.57 ± 3.22 s) and Fibrin (3.00 ± 0.44 s; 22.2 ± 9.75 s) compared to NaCl (158.16 ± 11.36 s; 127.5 ± 23.3 s). ALT levels were significantly higher in MAR-1 (27.66 ± 1 U/L) compared to Fibrin (24.16 ± 0.98 U/L) and NaCl (23.85 ± 0.80 U/L). Intrabdominal adhesions were significantly lower in MAR-1 (11.22% ± 5.5%) compared to NaCl (58.57% ± 11.83%). Degradation of the glue was observed and MAR-1 showed almost no traces of glue in the abdominal cavity as compared to the Fibrin (10% ± 5% 14 d; 7% ± 3% 21 d). Survival showed no significant differences between the groups.
CONCLUSION Compared to Fibrin, MAR-1 showed similar hemostatic properties, no adverse effects, and is biocompatible. Further studies on adhesion strength and biodegradability of synthetic sealants are warranted.
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Affiliation(s)
- Pramod Kadaba Srinivasan
- Institute for Laboratory Animal Science and Experimental Surgery, University Hospital, RWTH Aachen, 52074 Aachen, Germany
| | - Vera Sperber
- Institute for Laboratory Animal Science and Experimental Surgery, University Hospital, RWTH Aachen, 52074 Aachen, Germany
| | - Mamdouh Afify
- Institute for Laboratory Animal Science and Experimental Surgery, University Hospital, RWTH Aachen, 52074 Aachen, Germany
| | - Hirokazu Tanaka
- Institute for Laboratory Animal Science and Experimental Surgery, University Hospital, RWTH Aachen, 52074 Aachen, Germany
| | - Kenji Fukushima
- Institute for Laboratory Animal Science and Experimental Surgery, University Hospital, RWTH Aachen, 52074 Aachen, Germany
| | - Babette Kögel
- Institute for Laboratory Animal Science and Experimental Surgery, University Hospital, RWTH Aachen, 52074 Aachen, Germany
| | - Felix Gremse
- Experimental Molecular Imaging, University Hospital, RWTH Aachen, 52074 Aachen, Germany
| | - René Tolba
- Institute for Laboratory Animal Science and Experimental Surgery, University Hospital, RWTH Aachen, 52074 Aachen, Germany
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Guo J, Kim GB, Shan D, Kim JP, Hu J, Wang W, Hamad FG, Qian G, Rizk EB, Yang J. Click chemistry improved wet adhesion strength of mussel-inspired citrate-based antimicrobial bioadhesives. Biomaterials 2017; 112:275-286. [PMID: 27770631 PMCID: PMC5121090 DOI: 10.1016/j.biomaterials.2016.10.010] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Revised: 10/03/2016] [Accepted: 10/08/2016] [Indexed: 11/29/2022]
Abstract
For the first time, a convenient copper-catalyzed azide-alkyne cycloaddition (CuAAC, click chemistry) was successfully introduced into injectable citrate-based mussel-inspired bioadhesives (iCMBAs, iCs) to improve both cohesive and wet adhesive strengths and elongate the degradation time, providing numerous advantages in surgical applications. The major challenge in developing such adhesives was the mutual inhibition effect between the oxidant used for crosslinking catechol groups and the Cu(II) reductant used for CuAAC, which was successfully minimized by adding a biocompatible buffering agent typically used in cell culture, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), as a copper chelating agent. Among the investigated formulations, the highest adhesion strength achieved (223.11 ± 15.94 kPa) was around 13 times higher than that of a commercially available fibrin glue (15.4 ± 2.8 kPa). In addition, dual-crosslinked (i.e. click crosslinking and mussel-inspired crosslinking) iCMBAs still preserved considerable antibacterial and antifungal capabilities that are beneficial for the bioadhesives used as hemostatic adhesives or sealants for wound management.
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Affiliation(s)
- Jinshan Guo
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA
| | - Gloria B Kim
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA
| | - Dingying Shan
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA
| | - Jimin P Kim
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA
| | - Jianqing Hu
- School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, China
| | - Wei Wang
- Zhejiang Provincial Top Key Discipline of Bioengineering, College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, 315100, China
| | - Fawzi G Hamad
- Department of Materials Science and Engineering, The Pennsylvania State University, University Park, PA, 16802, USA
| | - Guoying Qian
- Zhejiang Provincial Top Key Discipline of Bioengineering, College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, 315100, China
| | - Elias B Rizk
- Department of Neurosurgery, College of Medicine, The Pennsylvania State University, Hershey, 17033, USA
| | - Jian Yang
- Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
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Tan P, Siah W, Malhotra R. Methods for prevention of complications during eyelid and peri-orbital surgery. EXPERT REVIEW OF OPHTHALMOLOGY 2016. [DOI: 10.1080/17469899.2016.1207529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Ke Z, Huang Q. Haem-assisted dityrosine-cross-linking of fibrinogen under non-thermal plasma exposure: one important mechanism of facilitated blood coagulation. Sci Rep 2016; 6:26982. [PMID: 27229173 PMCID: PMC4882584 DOI: 10.1038/srep26982] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Accepted: 05/12/2016] [Indexed: 12/14/2022] Open
Abstract
Although blood coagulation facilitated by non-thermal plasma has been reported several years ago, the insight to the involved mechanisms is still rather limited. In this work, we report our discovery of a new mechanism for the haem-promoted blood-coagulation caused by non-thermal plasma treatment. The reason for the haem role is due to that its oxidized form, namely, hematin, can promote the dityrosine cross-linking of fibrinogen, the most important coagulation protein, to form a membrane-like layer on the surface of the treated blood with plasma exposure. Both haem and non-thermal-plasma generated hydrogen peroxide are requisite for the cross-linking process. We confirmed that fibrinogen can coordinate with the haem iron to form a protein-haem complex which shows pseudo-peroxidase activity, and in the presence of hydrogen peroxide, the complex can induce the dityrosine formation between fibrinogen molecules, leading to the fibrin network necessary for the blood coagulation. Understanding of such an underlying mechanism can be useful to guide more efficient application of non-thermal plasma in the management of hemostasis, thrombosis and etc.
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Affiliation(s)
- Zhigang Ke
- Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China
| | - Qing Huang
- Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.,National Synchrotron Radiation Laboratory, University of Science &Technology of China, Hefei 230026, China
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Csukas D, Urbanics R, Moritz A, Ellis-Behnke R. AC5 Surgical Hemostat™ as an effective hemostatic agent in an anticoagulated rat liver punch biopsy model. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2015; 11:2025-31. [DOI: 10.1016/j.nano.2015.01.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2014] [Revised: 12/17/2014] [Accepted: 01/04/2015] [Indexed: 10/24/2022]
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Optimizing Intraoperative Bleeding Management. AORN J 2014; 100:123-4. [DOI: 10.1016/j.aorn.2014.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Accepted: 06/23/2014] [Indexed: 11/22/2022]
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How Hemostatic Agents Interact With the Coagulation Cascade. AORN J 2014; 100:148-59. [DOI: 10.1016/j.aorn.2013.12.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2013] [Revised: 11/30/2013] [Accepted: 12/07/2013] [Indexed: 11/21/2022]
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