A Universal Gelfoam 3-D Histoculture Method to Establish Patient-derived Cancer Cells (3D-PDCC) Without Fibroblasts from Patient-derived Xenografts.

BACKGROUND/AIM: The direct placement of patient tumors in 2-D culture on plastic or glass surfaces has inhibited the establishment of patient-derived cancer cells (PDCCs). The aim of the present study was to develop universal and efficient methods to prepare PDCCs. MATERIALS AND METHODS: Fragments of patient-derived xenograft (PDX) tumors established form colon cancer liver metastasis (1 mm3) were placed on Gelfoam and cultured in DMEM. RESULTS: PDX tumor fragments were cultured on Gelfoam. Cancer cells migrated from the explant and formed distinct 3-D structures in the Gelfoam. Each of the three PDCCs showed a distinct morphology. The cultures were essentially all cancer cells without fibroblasts, the opposite of what usually occurs in 2-D culture on plastic or glass. Gelfoam cultures could be readily passaged from one Gelfoam cube to anothers suggesting indefinite culture potential. CONCLUSION: A potentially universal method to establish PDCC using PDX tumors and 3-D Gelfoam histoculture was developed.

Comparing Gelfoam vs fat as a sealing material in stapedotomy: A prospective double-blind randomised clinical trial.

OBJECTIVES: One research aspect of stapes surgery is various materials that are used to seal the oval window. Several materials are used to seal the oval window, for example adipose tissue, perichondrium, vein graft, gelatin sponge (Gelfoam), blood clot and soft connective tissue. Up to now, there has been no randomised clinical trial that has evaluated the effects of different types of sealing material on hearing outcomes after stapedotomy. Hence, the present study aimed to find out which of these materials; fat or Gelfoam was associated with better hearing outcome, when used as a sealing material. DESIGN: This prospective, double-blind, randomised clinical trial was carried out on ears that had undergone stapedotomy. SETTING: Dastgheib Hospital affiliated to Shiraz University of Medical Sciences, a referral otology centre in southern Iran. PARTICIPANTS: A total of 176 primary stapedotomies were analysed. Fat harvested from the ear lobule was used in 86 ears and Gelfoam in 90 ears. MAIN OUTCOME MEASURES: Preoperative and postoperative pure tone audiometric data and incidence of sensorineural hearing loss were evaluated. RESULTS: Total of 90.7% of all ears in the fat group and 87.8% of ears in Gelfoam group achieved postoperative air-bone gap (ABG) within 20 dB, and this difference was not significant. There was no case of sensorineural hearing loss (defined as 10 dB or more reduction in BC threshold) in both groups in mean frequencies of 0.5-3 kHz. There were 9 cases of sensorineural hearing loss at 4 kHz in the fat group vs 4 in the Gelfoam group. The occurrence of sensorineural hearing loss in different frequencies was not significant between the two groups (P > 0.05). In addition, there was no case of dead ear in either group. CONCLUSIONS: We found similarity between hearing outcome in the Gelfoam and fat as sealing materials in stapedotomy. We believe that the first limitation of this study was the short-term follow-up in stapedotomy. The other issue is that one has to be cautious when using our result, which might not be applicable in larger fenestra stapedectomy.

The effects of different packing materials on healing and hearing after trauma to middle ear mucosa, an experimental study in rats.

PURPOSE: To compare the performance of Spongostan, Otopore, Spongostan soaked with dexamethasone and Spongostan soaked with Hyaluronic acid (HA) as middle ear packing material after mucosal trauma. METHODS: Twenty rats were divided into 4 groups. In control group (group 1), the middle ear cavities of animals were bilaterally packed with Spongostan; in group 2, with Otopore; in group 3, with Spongostan soaked with dexamethasone; and in group 4, with Spongostan soaked with HA. Auditory brainstem responses (ABRs) were performed preoperatively and 1 and 6 weeks postoperatively. Histological analyses were performed to evaluate the inflammatory reaction and wound healing in the middle ear cavity. RESULTS: ABR recordings demonstrate that threshold level changes from baseline were minor in Otopore and Spongostan soaked with dexamethasone packed ears. Threshold levels were higher in the Spongostan and Spongostan soaked with HA packed ears compared with both Otopore and Spongostan soaked with dexamethasone packed ears. Histological analyses showed that Spongostan caused inflammation more intense than Otopore and Spongostan soaked with dexamethasone. Residual material at postoperative week 6, new bone formation and adhesion were common in the Spongostan group compared with other groups. Fibrosis was more common in Spongostan group compared with other groups but the difference was not significant. CONCLUSION: Otopore appears to be safe and effective for use in otologic surgery. The inflammation, adhesion and new bone formation decreased when Spongostan was used with steroid or HA, when compared to Spongostan alone.

Evaluation of the safety and efficacy of a new hemostatic powder using a quantitative surface bleeding severity scale.

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.

Comparison between different isoelectric points of biodegradable gelatin sponges incorporating ß-tricalcium phosphate and recombinant human fibroblast growth factor-2 for ridge augmentation: A preclinical study of saddle-type defects in dogs.

BACKGROUND AND OBJECTIVE: It is well known that recombinant human fibroblast growth factor-2 (rhFGF-2) signaling plays an important role in tissue repair and regeneration. rhFGF-2 strongly binds to acidic gelatin via ionic linkages and is gradually released upon gelatin decomposition. On the other hand, the linkage between rhFGF-2 and basic gelatin is so weak that most rhFGF-2 is rapidly released from basic gelatin by simple desorption. Gelatin/ß-tricalcium phosphate (ß-TCP) sponges, which comprise 50 wt% gelatin and 50 wt% ß-TCP in a cross-linked structure, can release rhFGF-2 gradually owing to their electrical features. In a previous study, we reported that new bone height in the test group using rhFGF-2 with acidic gelatin/ß-TCP sponges was significantly greater than that in the control group using acidic gelatin/ß-TCP sponges alone in a ridge augmentation model in dogs. However, whether these results depend on controlled release by the gelatin/ß-TCP sponges remains controversial. In this study, we evaluated the effects of controlled release by comparing acidic and basic gelatin/ß-TCP sponges with different isoelectric points (IEP) on ridge augmentation in dogs. MATERIALS AND METHODS: Twelve weeks after extraction of the maxillary second and third incisors of six dogs, critically sized saddle-type defects (8 mm length × 4 mm depth) were surgically created bilaterally 2 mm from the mesial side of the canine. Acidic gelatin/ß-TCP sponges (IEP 5.0) soaked with 0.3% rhFGF-2 were applied to the defect in the acidic group, whereas basic gelatin/ß-TCP sponges (IEP 9.0) soaked with 0.3% rhFGF-2 were applied to the defect in the basic group. Twelve weeks after surgery, biopsy specimens were obtained and subjected to microcomputed tomography (micro-CT) and histological analyses. RESULTS: New bone area detected by micro-CT analysis was significantly smaller in the basic group than in the acidic group. New bone height calculated by histologic sections was significantly lower in the basic group than in the acidic group. The total tissue height was lower in the basic group than in the acidic group. However, the differences between both sites were not significant. CONCLUSIONS: These findings suggest that in ridge augmentation of saddle-type defects, controlled release of rhFGF-2 induces notably more alveolar bone formation than does short-term application of rhFGF-2.

Gelfoam haemostatic agent with or without autologous bone marrow-derived stem cells for the regeneration of critical-size mandibular defects in the rabbit.

This study evaluated the effect of Gelfoam sponge with and without autologous bone marrow-derived stem cells (BMSCs) on bone regeneration in critical-size mandibular defects. The study involved 56 New Zealand rabbits assigned to four groups (14 in each). The osseous defects in group I were irrigated with normal saline, those in group II were grafted with autogenous tibial bone, and those in group III were filled with Gelfoam sponge. Group IV defects were treated as for group III, but the interface between the Gelfoam sponge and bone surface was injected with BMSCs. At the end of 4weeks, seven rabbits in each group were euthanized; the remaining animals were euthanized at the end of the experiment, at 8 weeks postoperative. The percentage area of newly formed bone was significantly higher in group IV at week 4 (0.030±0.01%) and week 8 (0.060±0.03%) than in group I (0.01±0.00% and 0.02±0.00%, respectively) and group III (0.08±0.01% and 0.015±0.02%, respectively), but was lower than that in group II (0.038±0.02% and 0.082±0.01%, respectively). Thus, the combination of Gelfoam and autologous BMSCs promoted the regeneration of mandibular critical-size defects better than the use of Gelfoam alone. However, the amount of newly generated bone was lower than in defects grafted with autogenous bone.

Use of a flowable haemostat versus an oxidised regenerated cellulose agent in primary elective cardiac surgery: economic impact from a UK healthcare perspective.

BACKGROUND: Flowable haemostatic agents have been shown to be superior to non-flowable agents in terms of haemostatic control and need for transfusion products in patients undergoing cardiac surgery. We investigated the economic impact of the use of a flowable haemostatic agent (Floseal) compared with non-flowable oxidised regenerated cellulose (ORC) agent in primary elective cardiac surgery from the perspective of the UK National Health Service (NHS). METHODS: A cost-consequence framework based upon clinical data from a prospective trial and an observational trial and NHS-specific actual reference costs (2016) was developed to compare the economic impact of Floseal with that of ORC. The individual domains of care investigated comprised complications (major and minor) avoided, operating room time savings, surgical revisions for bleeding avoided and transfusions avoided. The cost impact of Floseal versus ORC on ICU days and extended bed days avoided was modelled separately. RESULTS: Compared with ORC, the use of Floseal would be associated with overall net savings to the NHS of £178,283 per 100 cardiac surgery patients who experience intraoperative bleeding requiring haemostatic therapy. Cost savings were apparent in all individual domains of care (complications avoided: £83,536; operating room time saved: £63,969; surgical revisions avoided: £34,038; and blood transfusions avoided: £22,317). Cost savings per 100 patients with Floseal over ORC in terms of ICU days avoided (n = 30) and extended bed days avoided (n = 51.7) were £57,960 and £21,965, respectively. A sensitivity analysis indicated that these findings remained robust when the model parameters representing the clinical benefit of Floseal over ORC were reduced by up to 20%. CONCLUSIONS: Despite higher initial acquisition costs, the use of flowable haemostatic agents achieves substantial cost savings over non-flowable agents in cardiac surgery. These cost savings commence during the operating theatre and appear to continue to be realised throughout the postoperative period.

Is the use of hemostatic matrix (Floseal) and alkylene oxide copolymer (Ostene) safe in spinal laminectomies? Peridural fibrosis assessment.

OBJECTIVE: Failed Back Syndrome (FBS) is unacceptable relief of pain or recurrence of symptoms in patients after spinal surgery, such as laminectomy. One possible cause of FBS is peridural fibrosis (PF). PF is the overproduction of scar tissue adjacent to the dura mater. Bleeding can cause PF after laminectomy. Ostene is an alkylene oxide copolymer material used to stop bleeding from bony surfaces. Floseal is a gelatin thrombin matrix sealant used to assist fibrin formation and to promote coagulation. METHODS: Total of 32 female Sprague-Dawley rats were evenly allotted to 4 experimental groups: laminectomy only, laminectomy + Ostene (Baxter International, Inc., Deerfield, IL, USA), laminectomy + Floseal (Baxter International, Inc., Deerfield, IL, USA), and laminectomy + Adcon-L (aap Implantate AG, Berlin, Germany). After performing total laminectomy, agents were placed over dura mater. Spinal column of test subjects was harvested 6 weeks after laminectomy. Histopathological examination of samples was based on Masson's trichrome and hematoxylin and eosin staining. PF observed in the groups was graded using system previously described by He et al. Statistically significant p value was defined as p < 0.005. RESULTS: Present study revealed that Adcon-L, Ostene, and Floseal groups had reduced PF compared with laminectomy only group (p = 0.001). Comparison of Ostene and Floseal groups with Adcon-L group yielded no significant difference. CONCLUSION: Reoperation as result of FBS has greater risk and often has poor outcome; surgeons must take precautions to avoid FBS, such as careful selection of appropriate patient and operation technique. Ostene and Floseal may be applied and left in the operation field safely during laminectomy to reduce occurrence of PF after procedure.

Repair of bone defects using adipose-derived stem cells combined with alpha-tricalcium phosphate and gelatin sponge scaffolds in a rat model.

OBJECTIVES: This study aimed to evaluate the potential of adipose-derived stem cells (ASCs) combined with a modified α-tricalcium phosphate (α-TCP) or gelatin sponge (GS) scaffolds for bone healing in a rat model. MATERIAL AND METHODS: Bone defects were surgically created in the femur of adult SHR rats and filled with the scaffolds, empty or combined with ASCs. The results were analyzed by histology and histomorphometry on days seven, 14, 30, and 60. RESULTS: Significantly increased bone repair was observed on days seven and 60 in animals treated with α-TCP/ASCs, and on day 14 in the group treated with GS/ASCs, when compared with the groups treated with the biomaterials alone. Intense fibroplasia was observed in the group treated with GS alone, on days 14 and 30. CONCLUSIONS: Our results showed that the use of ASCs combined with α-TCP or GS scaffolds resulted in increased bone repair. The higher efficacy of the α-TCP scaffold suggests osteoconductive property that results in a biological support to the cells, whereas the GS scaffold functions just as a carrier. These results confirm the potential of ASCs in accelerating bone repair in in vivo experimental rat models. These results suggest a new alternative for treating bone defects.

Repair of bone defects using adipose-derived stem cells combined with alpha-tricalcium phosphate and gelatin sponge scaffolds in a rat model

Abstract Objectives This study aimed to evaluate the potential of adipose-derived stem cells (ASCs) combined with a modified α-tricalcium phosphate (α-TCP) or gelatin sponge (GS) scaffolds for bone healing in a rat model. Material and Methods Bone defects were surgically created in the femur of adult SHR rats and filled with the scaffolds, empty or combined with ASCs. The results were analyzed by histology and histomorphometry on days seven, 14, 30, and 60. Results Significantly increased bone repair was observed on days seven and 60 in animals treated with α-TCP/ASCs, and on day 14 in the group treated with GS/ASCs, when compared with the groups treated with the biomaterials alone. Intense fibroplasia was observed in the group treated with GS alone, on days 14 and 30. Conclusions Our results showed that the use of ASCs combined with α-TCP or GS scaffolds resulted in increased bone repair. The higher efficacy of the α-TCP scaffold suggests osteoconductive property that results in a biological support to the cells, whereas the GS scaffold functions just as a carrier. These results confirm the potential of ASCs in accelerating bone repair in in vivo experimental rat models. These results suggest a new alternative for treating bone defects.

The Effect of PRP-enriched Gelfoam on Chronic Tympanic Membrane Perforation: A Double-blind Randomized Clinical Trial.

OBJECTIVE: To evaluate the effect of PRP-enriched gelfoam on the healing of chronic TM perforation in comparison with gelfoam alone. METHODS: In this double-blind randomized clinical trial Patients with chronic tympanic membrane were randomly allocated to two groups; intervention group underwent tympanoplasty with platelet rich plasma (PRP)- enriched gel foams and control group underwent operation with conventional gel foams alone. Patients information was recorded 4 and 12 months after surgery. RESULTS: Eventually 24 patients (12 males and 12 females) with a mean age of 43.33 ± 12.34 years in intervention and 41.33 ± 10.02 years in control group underwent analysis (p = 0.667). Complete TM healing was seen in 8 (66.67%) patients in intervention group and 3 (25%) patients in control group three months after intervention (p = 0.031, OR = 5.98). CONCLUSION: Addition of PRP to conventional gelfoams used in TM perforation repair increases the complete healing rate of TM perforation with less morbidity and complications.

Safety and Efficacy of Chitosan-Dextran Hydrogel in the Middle Ear in an Animal Model.

OBJECTIVES: To investigate the efficacy of chitosan-dextran hydrogel (CDH) in preventing postoperative adhesions between the tympanic membrane (TM) and intratympanic structures, and to evaluate its ototoxicity in an animal study. METHODS: In the first step, ototoxicity was evaluated with 7 male albino guinea pigs (GPs) via auditory brainstem responses (ABR) before and 4 weeks after unilateral intratympanic injection of CDH and saline solution contralaterally. In the second step, 12 GPs underwent bilateral ear surgery. The middle ear (ME) mucosa was abraded, and the cavity was filled with CDH on one side and packed with Gelfoam on the contralateral side. A control group of 6 GPs underwent the same procedure except that no material was applied in the ME. The animals were euthanized at the end of the 7th week, and otomicroscopic findings were noted and the temporal bones harvested for the histologic examination. The findings were scored and compared. RESULTS: There was no statistically significant difference between the pre- and postoperative ABR thresholds. In the otomicroscopic findings, the most prominent difference between the two groups was the presence of retraction of the TM in the Gelfoam group. The histopathologic findings revealed a higher degree of inflammation in the Gelfoam group compared with the CDH group. CONCLUSION: This study demonstrated that CDH has no ototoxic effects in GPs. Its use as an ME packing material revealed significantly less TM retraction and inflammatory reaction compared with Gelfoam.

The effect of hemostatic agents and tissue adhesive on injured peripheral nerve healing in rats - Part I. Electrophysiological study.

BACKGROUND: In the practice of maxillofacial surgery, bleeding and nerve injury have common problems. In the control of bleeding, hemostatic agents and tissue adhesives have been frequently used. The effect of these hemostatic agents and tissue adhesives on the injured neural tissues has not been known. OBJECTIVES: In this study, we aimed to investigate the effects of hemostatic agents and tissue adhesive on injured nerve tissues. MATERIAL AND METHODS: Forty-two rats randomly divided into seven groups: Control, Oxidized Regenerated Cellulose (ORC), Gelatine Sponge (GS), Bovine Collagen (BC), Ankaferd BloodStopper (ABS), Glutaraldehyde Surgical Adhesive (BioGlue®) and N-butil-2 cyanoacrylate (Glubran®2). The left sciatic nerves were crushed and surrounded by hemostatic agents and tissue adhesives. At the end of 12 weeks, the surgical site was reopened and electrophysiological recordings were performed. RESULTS: In the ORC, GS, and BC groups, the compound action potential (CAP) values were lower compared to the control group (p < 0.05). Although the values of CAP in the ABS group were higher than in the control group while CAP values in the BioGlue and Glubran®2 groups were lower than the control group, there was no statistical significance between the experimental and control groups (p > 0.05). In the ORC, BC, GS, and Glubran®2 groups, the nerve conduction velocities (NCV) values were lower than in the control group (p < 0.05). In the ABS and BioGlue groups, NCV values were lower compared to the control group but no significant differences were found (p > 0.05). CONCLUSIONS: The present study provides evidence that ABS is the most suitable hemostatic agent due to its favorable effect on the healing of injured neural tissues. BioGlue is also a suitable surgical agent with no adverse effects.

Gelatin matrix use reduces postoperative bleeding after total knee arthroplasty.

Bleeding after total knee arthroplasty can result in significant morbidity and increases the need for blood transfusion. The proper use of intraoperative adjunctive topical hemostatic agents can enhance hemostasis perioperatively, potentially reducing blood transfusions. In this prospective study, 157 consecutive patients undergoing primary total knee arthroplasty received FLOSEAL (FLOSEAL Hemostatic Matrix; Baxter Healthcare Corporation, Hayward, California), a gelatin thrombin hemostatic matrix, 5 mL (74 patients) or 10 mL (83 patients). All patients received warfarin as thromboprophylaxis starting the day after surgery. Data were extracted via hospital chart review from 100 consecutive patients who underwent total knee arthroplasty and immediately preceded the FLOSEAL groups and did not receive FLOSEAL (control group). Postoperative drainage was significantly lower in the FLOSEAL 5 mL (236.9 mL) and 10 mL (120.5 mL) groups compared with the control group (430.8 mL; P<.0001 for both). The FLOSEAL 10 mL group had significantly less drainage than the FLOSEAL 5 mL group (P<.0001). The predicted probability of transfusion in the FLOSEAL 5 mL group was not significantly different compared with the control group (6.0% vs 7.6%, P=.650). The predicted probability of transfusion was lower in the FLOSEAL 10 mL group compared with the control group (0.5% vs 5.5%; P=.004). Within the FLOSEAL 10 mL group, application of FLOSEAL either before or after tourniquet release had a similarly significant effect on drainage volume and predicted probability of blood transfusion. No differences in outcomes were observed by type of anesthesia used. No adverse events occurred related to FLOSEAL use.

Slow release of basic fibroblast growth factor (b-FGF) enhances mechanical properties of rat trachea.

AIM: Severe tracheomalacia is a life-threatening disease, but symptoms usually improve with growth. The aims of this study were to investigate how slow release basic-Fibroblast Growth Factor (b-FGF) acts on tracheal cartilage, and whether growth-promoted trachea is more resistant against an increase in externally-applied pressure. METHODS: Biodegradable gelatin hydrogel sheets soaked in 10 µl of distilled water (sham) or 0.5 or 5 µg/10 µl of b-FGF solution were inserted behind the cervical trachea of three-week-old male Wistar rats. The cervical trachea was harvested 4 weeks later. Extratracheal pressure was increased from 0 to 40 cmH2O in a chamber, while video-recording the internal lumen. The luminal area at each pressure was expressed as a proportion to that at 0 cmH2O. The amounts of collagen type II and glycosaminoglycan were measured by ELISA. RESULTS: The luminal areas at 40 cmH2O in the control (no intervention), sham, and each of the b-FGF groups were 0.65, 0.62, 0.72, and 0.73, respectively. The amounts of collagen type II and glycosaminoglycan in each group were 127, 136, 193, 249 µg/mg, respectively, and 15, 16, 19, 33 µg/mg, respectively. There were significant differences between the control group and the FGF 5 group (P=0.02, 0.01, 0.01, for luminal area, collagen, and glycosaminoglycan, respectively). CONCLUSION: 5 µg of slow-release b-FGF promotes matrix production (collagen type II and glycosaminoglycan). The growth-enhanced trachea was more resistant to collapse, suggesting that slowly released b-FGF might be useful in patients with severe tracheomalacia.

Cancer cells mimic in vivo spatial-temporal cell-cycle phase distribution and chemosensitivity in 3-dimensional Gelfoam® histoculture but not 2-dimensional culture as visualized with real-time FUCCI imaging.

The phase of the cell cycle can determine whether a cancer cell can respond to a given drug. We previously reported monitoring of real-time cell cycle dynamics of cancer cells throughout a live tumor, intravitally in live mice, using a fluorescence ubiquitination-based cell-cycle indicator (FUCCI). Approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G0/G1 phase. Longitudinal real-time imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of an established tumor. Moreover, resistant quiescent cancer cells restarted cycling after cessation of chemotherapy. These results suggested why most drugs currently in clinical use, which target cancer cells in S/G2/M, are mostly ineffective on solid tumors. In the present report, we used FUCCI imaging and Gelfoam® collagen-sponge-gel histoculture, to demonstrate in real time, that the cell-cycle phase distribution of cancer cells in Gelfoam® and in vivo tumors is highly similar, whereby only the surface cells proliferate and interior cells are quiescent in G0/G1. This is in contrast to 2D culture where most cancer cells cycle. Similarly, the cancer cells responded similarly to toxic chemotherapy in Gelfoam® culture as in vivo, and very differently than cancer cells in 2D culture which were much more chemosensitive. Gelfoam® culture of FUCCI-expressing cancer cells offers the opportunity to image the cell cycle of cancer cells continuously and to screen for novel effective therapies to target quiescent cells, which are the majority in a tumor and which would have a strong probability to be effective in vivo.

Incorporation of a prolyl hydroxylase inhibitor into scaffolds: a strategy for stimulating vascularization.

Clinical applications of tissue engineering are constrained by the ability of the implanted construct to invoke vascularization in adequate extent and velocity. To overcome the current limitations presented by local delivery of single angiogenic factors, we explored the incorporation of prolyl hydroxylase inhibitors (PHIs) into scaffolds as an alternative vascularization strategy. PHIs are small molecule drugs that can stabilize the alpha subunit of hypoxia-inducible factor-1 (HIF-1), a key transcription factor that regulates a variety of angiogenic mechanisms. In this study, we conjugated the PHI pyridine-2,4-dicarboxylic acid (PDCA) through amide bonds to a gelatin sponge (Gelfoam(®)). Fibroblasts cultured on PDCA-Gelfoam were able to infiltrate and proliferate in these scaffolds while secreting significantly more vascular endothelial growth factor than cells grown on Gelfoam without PDCA. Reporter cells expressing green fluorescent protein-tagged HIF-1α exhibited dose-dependent stabilization of this angiogenic transcription factor when growing within PDCA-Gelfoam constructs. Subsequently, we implanted PDCA-Gelfoam scaffolds into the perirenal fat tissue of Sprague Dawley rats for 8 days. Immunostaining of explants revealed that the PDCA-Gelfoam scaffolds were amply infiltrated by cells and promoted vascular ingrowth in a dose-dependent manner. Thus, the incorporation of PHIs into scaffolds appears to be a feasible strategy for improving vascularization in regenerative medicine applications.

Use of floseal hemostatic matrix for control of hemostasis during laparoscopic cholecystectomy for acute cholecystitis: a multicenter historical control group comparison (the GLA study gelatin matrix for acute cholecystitis).

BACKGROUND: In patients with acute cholecystitis undergoing laparoscopic cholecystectomy, bleeding is a common complication that can reduce procedural visibility and worsen outcome. Insufficient hemostasis can also lead to postoperative bleeding that can, in rare cases, be fatal. Topical hemostatic agents are used to ensure adequate hemostasis during laparoscopic cholecystectomy. SUBJECTS AND METHODS: This prospective, open-label, nonrandomized, historical control group study investigated the use of Floseal(®) (Baxter International, Inc., Deerfield, IL) hemostatic matrix as an adjunct to surgical techniques to achieve hemostasis of the resected areas in patients undergoing laparoscopic cholecystectomy for acute cholecystitis. The primary end point was the rate of complete hemostasis 10 minutes after laparoscopic application of Floseal to the gallbladder bed. Secondary end points included complete hemostasis rates at 2, 4, and 6 minutes, surgery time, laparoscopic procedure to open laparotomy conversion rate, postoperative bleeding rate, and mortality and safety outcomes over the entire follow-up period. RESULTS: From April to November 2011, 101 consecutive patients were enrolled (51 men; mean age, 61.5±6.2 years). The historical control group of 100 age- and gender-matched patients with acute cholecystitis had undergone laparoscopic cholecystectomy without hemostatic agent. In the Floseal group, bleeding ceased within 10 minutes after laparoscopic application of the hemostatic agent to the gallbladder bed in all patients. The conversion rate was significantly lower in the Floseal group than in the control group (4 versus 12 patients, P<.05). CONCLUSIONS: Floseal in acute cholecystitis is safe, is effective in controlling bleeding, and results in a lower conversion rate compared with cholecystectomy without hemostatic agents.

Total thyroidectomy with harmonic scalpel combined to gelatin-thrombin matrix hemostatic agent: is it safe and effective? A single-center prospective study.

INTRODUCTION: Hemostasis during thyroidectomy is essential; however, the safest, most efficient and cost-effective way to achieve this is unclear. The aim of this study was to evaluate the outcome of total thyroidectomy (TT) performed with combination of harmonic scalpel (HS) and Floseal. METHODS: Patients undergone TT were divided into two groups: HS + Floseal and traditional hemostasis groups. The primary endpoint was 24-h drain output and blood-loss requiring reintervention. Secondary endpoints included surgery duration, postsurgical complications and hypocalcemia rates. RESULTS: Between September 2012 and January 2014, 165 patients were enrolled (100 to HS + Floseal, 65 to standard hemostasis); 80.5% female; mean age 42.3 years. The 24-h drain output was lower in the HS + Floseal group compared with standard TT. HS + Floseal also had a shorter mean surgery time (p < 0.0001) vs standard TT. No differences in post-surgical complications and in hypocalcemiarates between groups. CONCLUSION: combination of Floseal plus the HS is effective and safe for TT and it provides a complementary hemostatic approach.