Autologous peripheral blood-derived orthobiologics:Different types and their effectiveness in managing knee osteoarthritis

Knees are the most commonly impacted weight-bearing joints in osteoarthritis(OA),affecting millions of people worldwide.With increasing life spans and obesity rates,the incidence of knee OA will further increase,leading to a significant increase in the economic burden.Conventional treatment modalities utilized to manage knee OA have limitations.Over the last decade,the role of various autologous peripheral blood-derived orthobiologics(APBOs)for the treatment of knee OA has been extensively investigated.This editorial provided an overview and focused on defining and shedding light on the current state of evidence based on the most recent published clinical studies concerning the use of APBO for the management of knee OA.While numerous studies have demonstrated promising results for these preparations,a notable gap exists in the comparative analysis of these diverse formulations.This absence of head-to-head studies poses a considerable challenge for physicians/surgeons in determining the optimal preparation for managing knee OA and achieving sustained longterm results.Thus,more adequately powered,multicenter,prospective,doubleblind,randomized controlled trials with longer follow-ups are needed to establish the long-term efficacy and to aid physicians/surgeons in determining the optimal APBO for the management of knee OA.

Rescuing“hopeless”avulsed teeth using autologous platelet-rich fibrin following delayed reimplantation:Two case reports

BACKGROUND Tooth avulsion is one of the most severe types of dental trauma.Most avulsed teeth undergo long-term ankylosis and replacement resorption after delayed reimplantation and exhibit a poor prognosis.The aim of this work was to improve the success rate of avulsed teeth after delayed reimplantation using autologous platelet-rich fibrin(PRF).CASE SUMMARY Case 1 was a 14-year-old boy who fell and knocked out his left upper central incisor 18 h prior to his arrival at the department.The diagnoses were avulsion of tooth 21,lateral luxation of tooth 11 and alveolar fracture of teeth 11 and 21.In case 2,a 17-year-old boy fell 2 h prior to his presentation to the hospital,and his left upper lateral incisor was completely knocked out of the alveolar socket.The diagnoses included avulsion of tooth 22,complicated crown fracture of tooth 11and complicated crown-root fracture of tooth 21.The avulsed teeth were reimplanted along with autologous PRF granules and splinted using a semiflexible titanium preshaped labial arch.The root canals of the avulsed teeth were filled with calcium hydroxide paste,and root canal filling was performed 4 wk after reimplantation.The reimplanted teeth showed no symptoms of inflammatory root resorption or ankylosis at the 3-,6-,and 12-mo follow-up examinations after reimplantation with autologous PRF.In addition to the avulsed teeth,the other injured teeth were treated using corresponding conventional treatment methods.CONCLUSION These cases provide examples of the successful use of PRF to reduce pathological root resorption of the avulsed teeth,and the application of PRF may provide new healing opportunities for traditionally“hopeless”avulsed teeth.

Platelet rich fibrin is not a barrier membrane!Or is it?

Platelet-rich fibrin(PRF)is widely used in dentistry and other fields of medicine,and its use has become popular in dental implantology.In several published studies,PRF has been used as a barrier membrane.A barrier membrane is a sheet of a certain material that acts as a biological and mechanical barrier against the invasion of cells that are not involved in bone formation,such as epithelial cells.Among the basic requirements of a'barrier membrane,occlusivity,stiffness,and space maintenance are the criteria that PRF primarily lacks;therefore,it does not fall under the category of barrier membranes.However,there is evidence that PRF membranes are useful in significantly improving wound healing.Does the PRF membrane act as a barrier?Should we think of adding or subtracting some points from the ideal requirements of a barrier membrane,or should we coin a new term or concept for PRF that will incorporate some features of a barrier membrane and be a combination of tissue engineering and biotechnology?This review is aimed at answering the basic question of whether the PRF membrane should be considered a barrier membrane or whether it is something more beyond the boundaries of a barrier membrane.

Chitosan conduits enriched with fibrin-collagen hydrogel with or without adipose-derived mesenchymal stem cells for the repair of 15-mm-long sciatic nerve defect

Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair.Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance.In this study,we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model.Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks.Nevertheless,the molecular assessment in the early regeneration phase(7,14,and 28 days)has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones.Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1,a growth factor that plays an important role in Schwann cell transdifferentiation.The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2,VEGF-A,BDNF,c-Jun,and ATF3.

Treatment of corneal dermoid with lenticules from small incision lenticule extraction surgery:a surgery assisted by fibrin glue

AIM:To observe the clinical efficacy of the combined use of small incision lenticule extraction(SMILE)-derived lenticule patches in corneal dermoid excision,with fixation of the lenticule patches assisted by fibrin glue.METHODS:Seventeen eyes of 17 patients with corneal dermoid were treated with dermoid removal combined with SMILE-derived lenticule transplantation.All lenticule patches were fixed by fibrin glue.Ocular changes were assessed using slit lamp microscopy and anterior-segmental optical coherence tomography.The best-corrected visual acuity(BCVA)and ocular dioptric variations were examined preoperatively and postoperatively.Intraocular pressure(IOP)was also monitored in all visited time.RESULTS:Totally,18 lenticule patches were used on 17 eyes of 17 cornea dermoid patients.The mean follow-up time was 11.47±5.28mo.All lenticule patches we resuccessfullyg lued,kept on its location and maintained transparent during the follow-up time,with a consecutive epithelial cover for 1wk.Nine of the patients could coordinate visual and optometry exam well.Their preoperative BCVA is 0.60±0.35 in decimal,significantly improved to 0.80±0.26 in decimal at 6mo postoperatively(Z=-2.392,P=0.017),but the changes of their corneal astigmatism diopters showed no significance,with 2.22±1.91 D preoperatively,and 2.28±1.31 D at 6mo postoperatively(Z=-0.135,P=0.893).Limbal pannus formation occurred in 4(23.52%)cases and decreased with the application of tacrolimus eyedrops.IOP increased in 2(11.76%)cases,but well decreased by timolol maleate eyedrops.All the adult patients or guardians of minor patients were satisfied with the cosmetic improvement.CONCLUSION:Dermoid excision combined with transplantation of SMILE-derived lenticule patches using fibrin glue is a safe and effective novel tectonic keratoplasty procedure for corneal dermoid.

Hypoxic pre-conditioned adipose-derived stem/progenitor cells embedded in fibrin conduits promote peripheral nerve regeneration in a sciatic nerve graft model

Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells(ADSPCs)in peripheral nerve recovery.Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs.This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned(2%oxygen for 72 hours)autologous ADSPCs(n=9).This treatment mode was compared with three others:fibrin conduit seeded with ADSPCs cultivated under normoxic conditions(n=9);non-cell-carrying conduit(n=9);and nerve autograft only(n=9).A 16-week follow-up included functional testing(sciatic functional index and static sciatic index)as well as postmortem muscle mass analyses and morphometric nerve evaluations(histology,g-ratio,axon density,and diameter).At 8 weeks,the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups,indicating faster functional regeneration.Furthermore,histologic evaluation showed significantly increased axon outgrowth/branching,axon density,remyelination,and a reduced relative connective tissue area.Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts.Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice.

直接免疫荧光Fibrin线性阳性的扁平苔藓样类天疱疮1例

扁平苔藓样类天疱疮是一种自身免疫性表皮下疱性疾病,仅累计口腔黏膜病损的病例较为少见,病程漫长,且反复迁延。本文报道了1例直接免疫荧光纤维蛋白Fibrin线性阳性的扁平苔藓样类天疱疮的诊疗过程。

Clinical association between coagulation indicators and bone metastasis in patients with gastric cancer

BACKGROUND Bones are one of the most common target organs for cancer metastasis.Early evaluation of bone metastasis(BM)status is clinically significant.Cancer patients often experience a hypercoagulable state.AIM To evaluate the correlation between coagulation indicators and the burden of BM in gastric cancer(GC).METHODS We conducted a single-center retrospective study and enrolled 454 patients.Clinical information including routine blood examination and coagulation markers were collected before any treatment.Patients were grouped according to the status of BM.Receiver operating characteristic curves were used to assess diagnostic performance and determine the optimal cutoff values of the above indicators.Cutoff values,sensitivity and specificity were based on the maximum Youden index.Univariate and multivariate logistic regression analyses were used to evaluate the relationships between biomarkers and BM.RESULTS Of the 454 enrolled patients,191 patients were diagnosed with BM.The receiver operating characteristic curve analysis suggested that prothrombin time(PT)Wang X et al.Coagulation indicators predict bone metastasis WJGO https://www.wjgnet.com 1254 July 15,2023 Volume 15 Issue 7[cutoff:13.25;sensitivity:0.651;specificity:0.709;area under receiver operating characteristic curve(AUC)=0.738],activated partial thromboplastin time(aPTT)(cutoff:35.15;sensitivity:0.640;specificity:0.640;AUC=0.678)and fibrin degradation products(FDP)(cutoff:2.75;sensitivity:0.668;specificity:0.801;AUC=0.768)act as novel predictors for BM.Based on multivariate logistic regression analysis,the results showed the independent correlation between PT[odds ratio(OR):3.16;95%confidence interval(CI):1.612-6.194;P=0.001],aPTT(OR:2.234;95%CI:1.157-4.313;P=0.017)and FDP(OR:3.17;95%CI:1.637-6.139;P=0.001)and BM in patients with GC.Moreover,age,carcinoembryonic antigen,erythrocyte and globulin were found to be significantly associated with BM.CONCLUSION Coagulation markers,namely PT,aPTT and FDP,might be potential predictors for screening BM in patients with GC.

Application of advanced platelet-rich fibrin for through-and-through bony defect during endodontic surgery:Three case reports and review of the literature

BACKGROUND The use of advanced platelet-rich fibrin(A-PRF)membranes for guided bone and tissue regeneration in through-and-through defects after endodontic surgery was explored in three cases.CASE SUMMARY Herein,three patients presented to the endodontic clinic suffering from apical periodontitis,associated with large bone resorption and related to previously endodontically treated teeth.Periapical surgery was indicated in these cases and the osteotomy site was covered by A-PRF membrane.Cone-beam computed tomography(CBCT)was used to assess the cases before and after the surgery.CONCLUSION Four months post-surgery,the recall CBCT scan showed complete obliteration of the osteotomy with newly formed bone.A-PRF membrane showed promising results and was an advantageous addition to surgical endodontic treatment.

Evaluating the Benefits of Platelet Rich-Fibrin in Periodontal Regeneration: A Literature Review

Introduction: Platelet Rich-Fibrin (PRF) is a biological matrix derived from a patient’s own blood, rich in growth factors and platelets. Its use in various periodontal and non-periodontal procedures is gaining recognition due to its potential in promoting tissue regeneration. The purpose of this review was to evaluate the benefits of using PRF in intra-bony defect regeneration, guided-bone regeneration, and sinus floor elevation. Methods: The study searched PubMed for manuscripts published between 2017 and 2022 to better understand the clinical and radiological effects of PRF. The manuscripts were divided into the following sections: intra-bony defect regeneration, guided-bone regeneration, and sinus floor elevation. Results: In intra-bony defects, PRF improved clinical and radiological parameters when compared with OFD alone, with a significant difference in wound healing at 7 days. In GBR, a CBCT evaluation shows no statistical difference between the PRF-autogenous bone complex group and the bovine bone-collagen membrane complex regarding volume change of the augmented bone with a 16% rate of bone loss following a 6-month healing period. Also, a slight increase in bone thickness has been seen when liquid PRF is used. In sinus floor elevation, results revealed no differences in graft volume between PRF group and control group at any of the evaluated time points. Although higher implant stability immediately postoperatively, higher new bone formation, the lesser amount of residual graft and earlier implant placement. Conclusion: Platelet Rich-Fibrin is widely accepted for use in periodontal surgery and dentistry due to its minimally invasive nature and low risk of adverse effects, with positive results in tissue regeneration. There is evidence that PRF leads to improved and faster healing, as well as cost-effective regenerative procedures compared to other treatments.

The Role of Leukocyte and Platelet-Rich Fibrin in Enhancing the Healing of Extraction Sockets: An Overview of the Literature

Introduction: Leukocyte and platelet-rich fibrin (L-PRF) is an emerging material in dentistry, however, there are controversies surrounding its effectiveness. Despite the amount of literature available, debates regarding its effect continue. This review aims to summarize and clarify the data surrounding the use of L-PRF in promoting the healing of extraction sockets, which may offer a better outcome for future treatments. Purpose: The purpose of this review is to evaluate the current literature on the use of L-PRF in promoting the healing of extraction sockets, and to provide a comprehensive overview of the available evidence. Methods: A comprehensive computer-based search of databases such as PubMed, Medline, and Cochrane Library was conducted. Results: The results of this review suggest that L-PRF has shown promise in promoting early healing of extraction sockets, but the evidence for its effectiveness over a longer period is limited. Conclusion: Although L-PRF has shown promising results in the early healing periods, its effectiveness over a longer healing period cannot be confirmed based on the available data. More clinical trials with standardized protocols and consistent measurement methods are needed to establish the role of L-PRF in enhancing the healing of extraction sockets.

独活寄生汤含药血清对PLGA/Fibrin复合支架培养兔髓核细胞代谢影响的研究

目的探讨独活寄生汤含药血清对兔髓核细胞在PLGA/Fibrin复合支架培养代谢的影响。方法应用冻干法制备PLGA/Fibrin支架培养兔髓核细胞,按照不同浓度独活寄生汤含药血清分为A组(100μg/ml)、B组(200μg/ml)、C组(500μg/ml)及D组(空白对照)。通过MTT分析细胞增殖分化,DMMB法检测硫酸糖胺多糖(GAG),qRT-PCR检测COLⅡ、aggrecan差异,组织学观察髓核细胞在PLGA/Fibrin复合支架微孔环境生长形态学改变。结果培养1、7及14d后A、B、C3组髓核细胞活性、GAG水平、COLⅡ及Aggrecan mRNA表达均高于D组,且随着独活寄生汤含药血清浓度递增,细胞活性及基质表达有显著增加。培养2周后HE染色显示A、B、C3组较D组微孔支架吸附、积聚更多髓核细胞生长。结论PLGA/Fibrin复合支架能满足兔髓核细胞的黏附、伸展及繁殖要求,并为维持细胞的体外增殖和代谢活动提供适宜的微环境。独活寄生汤能够更好提高髓核细胞分化增殖能力,促进细胞基质分泌,从而减缓了椎间盘的退变。

PRF植入兔拔牙创内的实验研究

目的探讨PRF对拔牙窝的促进骨再生作用及牙槽嵴保存的影响。方法①实验动物模型:将24只新西兰大白兔随机分为4组(A、B、C、D组),每组6只,拔除一侧下颌切牙。抽取大白兔自体外周血液,离心后制成PRF。A组拔牙窝内植入PRF/nano-HA混合物;B组拔牙窝内植入PRF;C组拔牙窝内植入nano-HA;D组拔牙窝作为空白对照。分别于术后4周、12周处死动物,取材。②观察:将标本脱钙脱水石蜡包埋行组织学切片,显微镜下观察骨愈合情况。结果术后4周,拔牙窝内新生骨组织数量质量A组>B组>C组>D组(空白组)。术后12周,A组成骨质量最好,B、C组骨改建情况类似,均优于D组。结论①PRF能够促进骨组织的修复。②PRF联合nano-HA具有保存拔牙窝牙槽嵴高度的功能,可作为牙槽骨保存的移植材料。

PREPARATION AND CHARACTERIZATION OF TWO MONOCLONAL ANTIBODIES AGAINST A_α CHAIN'S C TERMINUS OF FIBRINOGEN

Two monoclonal antibodies (McAbs) against Aα chain's C terminus offibrinogen (Fg) have been prepared and designated SZ-78 and SZ-79. Both theantigens in binding assay and immunoblot analysis showed that the two McAbs recognized the epitopes located in residues 549-560 of the Aαchain. The two McAbs couldaccelerate rate of fibrin polymer assembly both in the purified system and in the humanplasma. From the pictures of transmission electronmicroscope, the average diametersof the fibers increase significantly to an average diameters of 375 nm after incubationwith the McAbs, while it was only 75nm without addition of the McAbs. There were al-so more branchings of fibers with addition of McAbs. These observations demonstratethat the amino acid sequences ofα 549-560 in the COOH terminus of the Aα chain mayplay an important role in the assembly of a fibrin clot, presumably being involved in lat-eral aggregation of protofibrils. The preparation of the McAbs supplies a usuful probe for the investigation of the

Evolution,current status and advances in application of platelet concentrate in periodontics and implantology

Platelet concentrates(PC) [platelet-rich plasma(PRP) and platelet-rich fibrin(PRF)] are frequently used for surgical procedures in medical and dental fields,particularly in oral and maxillofacial surgery,plastic surgery and sports medicine.The objective of all these technologies is to extract all the elements from a blood sample that could be used to improve healing and promote tissue regeneration.Although leukocyte rich and leukocyte poor PRP's have their own place in literature,the importance of non-platelet components in a platelet concentrate remains a mystery.PC have come a long way since its first appearance in 1954 to the T-PRF,A-PRF and i-PRF introduced recently.These PC find varied applications successfully in periodontics and implant dentistry as well.However,the technique of preparation,standing time,transfer process,temperature of centrifuge,vibration,etc.,are the various factors for the mixed results reported in the literature.Until the introduction of a proper classification of terminologies,the PC were known by different names in different countries and by different commercial companies which also created a lot of confusion.This review intends to clarify all these confusion by briefing the exact evolution of PC,their preparation techniques,recent advances and their various clinical and technical aspects and applications.

Antibacterial effects of platelet-rich fibrin produced by horizontal centrifugation

Platelet-rich fibrin(PRF)has been widely used owing to its ability to stimulate tissue regeneration.To date,few studies have described the antibacterial properties of PRF.Previously,PRF prepared by horizontal centrifugation(H-PRF)was shown to contain more immune cells than leukocyte-and platelet-rich fibrin(L-PRF).This study aimed to compare the antimicrobial effects of PRFs against Staphylococcus aureus and Escherichia coli in vitro and to determine whether the antibacterial effects correlated with the number of immune cells.Blood samples were obtained from eight healthy donors to prepare L-PRF and H-PRF.The sizes and weights of L-PRF and H-PRF were first evaluated,and their antibacterial effects against S.aureus and E.coli were then tested in vitro using the inhibition ring and plate-counting test methods.Flow-cytometric analysis of the cell components of L-PRF and H-PRF was also performed.No significant differences in size or weight were observed between the L-PRF and H-PRF groups.The H-PRF group contained more leukocytes than the L-PRF group.While both PRFs had notable antimicrobial activity against S.aureus and E.coli,H-PRF demonstrated a significantly better antibacterial effect than L-PRF.Furthermore,the antimicrobial ability of the PRF solid was less efficient than that of wet PRF.In conclusion,H-PRF exhibited better antibacterial activity than L-PRF,which might have been attributed to having more immune cells.

Platelet-rich plasma gel in combination with Schwann cells for repair of sciatic nerve injury

Bone marrow mesenchymal stem cells were isolated from New Zealand white rabbits, culture-expanded and differentiated into Schwann cell-like cells. Autologous platelet-dch plasma and Schwann cell-like cells were mixed in suspension at a density of 1 x 106 cells/mL, prior to introduction into a poly （lactic-co-glycolic acid） conduit. Fabricated tissue-engineered nerves were implanted into rabbits to bridge 10 mm sciatic nerve defects （platelet-rich plasma group）. Controls were established using fibrin as the seeding matrix for Schwann cell-like cells at identical density to construct tissue-engineered nerves （fibrin group）. Twelve weeks after implantation, toluidine blue staining and scanning electron microscopy were used to demonstrate an increase in the number of regenerating nerve fibers and thickness of the myelin sheath in the platelet-rich plasma group compared with the fibrin group. Fluoro-gold retrograde labeling revealed that the number of Fluoro-gold-positive neurons in the dorsal root ganglion and the spinal cord anterior horn was greater in the platelet-rich plasma group than in the fibrin group. Electrophysiological examination confirmed that compound muscle action potential and nerve conduction velocity were superior in the platelet-rich plasma group compared with the fibrin group. These results indicate that autologous platelet-rich plasma gel can effectively serve as a seeding matrix for Schwann cell-like cells to construct tissue-engineered nerves to promote perJpheral nerve regeneration.

Platelet-rich fibrin-induced bone marrow mesenchymal stem cell differentiation into osteoblast-like cells and neural cells

Bone marrow mesenchymal stem cells were allowed to develop for 14 days in a platelet-rich fibrin environment.Results demonstrated that platelet-rich fibrin significantly promoted bone marrow mesenchymal stem cell proliferation.In addition,there was a dose-dependent increase in Runt-related transcription factor-2 and bone morphogenetic protein-2 mRNA expression,as well as neuron-specific enolase and glial acidic protein.Results showed that platelet-rich fibrin promoted bone marrow mesenchymal stem cell proliferation and differentiation of osteoblast-like cells and neural cells in a dose-dependent manner.

Use of a combination strategy to improve neuroprotection and neuroregeneration in a rat model of acute spinal cord injury

Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied in clinical practice. In this study, we analyzed the combination of different strategies as a potential therapy for spinal cord injury. Immunization with neural derived peptides(INDP), inhibition of glial scar formation(dipyridyl: DPY), as well as the use of biocompatible matrix(fibrin glue: FG) impregnated with bone marrow mesenchymal stem cells(MSCs) were combined and then its beneficial effects were evaluated in the induction of neuroprotection and neuroregeneration after acute SCI. Sprague-Dawley female rats were subjected to a moderate spinal cord injury and then randomly allocated into five groups: 1) phosphate buffered saline; 2) DPY; 3) INDP + DPY; 4) DPY+ FG; 5) INDP + DPY + FG + MSCs. In all rats, intervention was performed 72 hours after spinal cord injury. Locomotor and sensibility recovery was assessed in all rats. At 60 days after treatment, histological examinations of the spinal cord(hematoxylin-eosin and Bielschowsky staining) were performed. Our results showed that the combination therapy(DPY+ INDP + FG+ MSCs) was the best strategy to promote motor and sensibility recovery. In addition, significant increases in tissue preservation and axonal density were observed in the combination therapy group. Findings from this study suggest that the combination theapy(DPY+ INDP + FG + MSCs) exhibits potential effects on the protection and regeneration of neural tissue after acute spinal cord injury. All procedures were approved by the Animal Bioethics and Welfare Committee(approval No. 178544; CSNBTBIBAJ 090812960)on August 15, 2016.

Reduction of the closure time of postoperative enterocutaneous fistulas with fibrin sealant

AIM: To assess whether the use of fibrin sealantshortens the closure time of postoperative enterocutaneous fistulas (ECFs). METHODS: The prospective case-control study included 70 patients with postoperative ECFs with an output of < 500 mL/d, a fistulous tract of > 2 cm and without any local complication. They were divided into study (n = 23) and control groups (n = 47). Esophageal, gastric and colocutaneous fistulas were monitored under endoscopic visualization, which also allowed fibrin glue application directly through the external hole. Outcome variables included closure time, time to resume oral feeding and morbidity related to nutritional support. RESULTS: There were no differences in mean age, fistula output, and follow-up. Closure-time for all patients of the study group was 12.5 ± 14.2 d and 32.5 ± 17.9 d for the control group (P < 0.001), and morbidity related to nutritional support was 8.6% and 42.5%, respectively (P < 0.01). In patients with colonic fistulas, complete closure occurred 23.5 ± 19.5 d after the first application of fibrin glue, and spontaneous closure was observed after 36.2 ± 22.8 d in the control group (P = 0.36). Recurrences were observed in 2 patients because of residual disease. One patient of each group died during follow-up as a consequence of septic complications related to parenteral nutrition. CONCLUSION: Closure time was significantly reduced with the use of fibrin sealant, and oral feeding was resumed faster. We suggest the use of fibrin sealant for the management of stable enterocutaneous fistulas.