Search

Developing a hemostatic material suitable for rapid hemostasis remains a challenge. This study presents a novel aminated gelatin sponge cross-linked with dialdehyde starch, exhibiting excellent biocompatibility and hemostatic ability. This aminated gelatin sponge features hydrophilic surface and rich porous structure with a porosity of up to 80 %. The results show that the aminated gelatin sponges exhibit superior liquid absorption capacity and can absorb up to 30-50 times their own mass of simulated body fluid within 5 min. Compared with the commercial gelatin hemostatic sponge and non-aminated gelatin hemostatic sponge, the aminated gelatin hemostatic sponge can accelerate the hemostatic process through electrostatic interactions, demonstrating superior hemostatic performance in both in vitro and in vivo hemostasis tests. The aminated gelatin sponge can effectively control the hemostatic time within 80 s in the in vivo rat femoral artery injury model, significantly outperforming both commercial and non-aminated gelatin sponges. In addition, the aminated gelatin sponge also exhibits good biocompatibility and certain antibacterial properties. The proposed aminated gelatin sponge has very good application prospects for the management of massive hemorrhage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 mm 3 ) 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., (Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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/β-tricalcium phosphate (β-TCP) sponges, which comprise 50 wt% gelatin and 50 wt% β-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/β-TCP sponges was significantly greater than that in the control group using acidic gelatin/β-TCP sponges alone in a ridge augmentation model in dogs. However, whether these results depend on controlled release by the gelatin/β-TCP sponges remains controversial. In this study, we evaluated the effects of controlled release by comparing acidic and basic gelatin/β-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/β-TCP sponges (IEP 5.0) soaked with 0.3% rhFGF-2 were applied to the defect in the acidic group, whereas basic gelatin/β-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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (© 2019 John Wiley & Sons Ltd.)

Graphene oxide (GO) is a promising hemostatic material because of its platelet stimulatory activity. However, our previous studies on cross-linked graphene sponges demonstrated that those sponges lost the GO function of platelet stimulation due to the pristine GO was reduced under the harsh reaction conditions. Accordingly, a mild cross-linking strategy is expected to preserve the oxygen-containing groups to further increase the hemostatic performance of the sponges. Here, we present a polydopamine (PDA) cross-linked GO sponge (DCGO) by using mild and facile wet chemistry. The obtained DCGO possessed a high surface charge (-31.3 ± 0.3 mV) and showed strong platelet stimulation. Moreover, this method strengthened the mechanical properties of the DCGO, which supported 350 times its own weight without deformation, thus ensuring its absorbability. For the synergy of platelet stimulation and physical absorption, DCGO achieved outstanding hemostatic performance. Bleeding stopped within 105 ± 15 s, which was 165 s faster than that of the un-cross-linked GO aerogel and 96 s faster than that of the cross-linked graphene sponge (CGS). The DCGO combines the advantages of both PDA and GO, thus supplying a new material and method for the field of trauma hemostasis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (© 2019 The Authors. Journal of Cardiac Surgery Published by Wiley Periodicals, Inc.)

Objective: Previous studies have not examined the potential role of endonasal hemostatic agents in facilitating growth of fungal species. We aim to determine the possibility of these to serve as a nutrient source for fungal growth., Methods: Cultures of Aspergillus, Fusarium, and Mucor were harvested and placed in solution in sterile saline at standardized high and low concentrations. Thrombin gelatin matrix, carboxyl methylcelluose, and potato starch derivative agents were prepared following manufacturer instructions and applied to two separate Petri dishes per agent. Each substrate was then inoculated with either high or low concentrations of fungal species. Negative and positive control plates with each organism were included. Dishes were sealed, incubated, and examined daily for fourteen days for microscopic and macroscopic growth., Results: Thrombin gelatin matrix was relatively resilient to growth, although Fusarium growth was noted on all packing material by day three. Carboxyl methylcellulose also supported growth of high-concentration Mucor appreciated on day five. The potato starch derivative supported fulminant growth of all fungal species., Conclusions: Endonasal hemostatic agents may be nutrient sources that facilitate growth of fungal species. This may be a consideration in a surgeon's decision to use a hemostatic agent. Prompt initial post-operative debridement may be warranted in select patients. Our findings serve as a model for further testing of fungal growth on other hemostatic materials. Future studies are needed to confirm the clinical significance of these findings in vivo., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Otomycosis is a common clinical condition seen in outpatient department of otorhinolaryngology. The treatment of the otomycosis is also very simple. However, sometime it is difficult to treat otomycosis along with mastoid cavity, chronic suppurative otitis media, immunocompromised patient, etc. with conventional treatment, called recalcitrant otomycosis. Here, we describe a technique of treatment for recalcitrant otomycosis., Materials and Methods: This is a prospective observational study/clinical trial carried out on 44 patients of recalcitrant otomycosis. They are divided into two groups, each of 22. One group treated with routine clotrimazole topical eardrops whereas other group treated with povidone iodine soaked gelfoam, placed in the external auditory canal., Results: There was no significance difference according to the age (P=0.134), gender (P=0.760) and causative agents (P=0.750) between treatment groups. The resolution of the symptoms showed statistically significant on itching (P=0.0001), otorrhoea (P=0.0033), fullness (P=0.0432) and earache (P=0.0259), whereas no statistical significant on hearing loss (P=0.0683), when treating with povidone iodine soaked gelfoam as compared to routine (clotrimazole) treatment. Resolution of signs like canal wall erythema (P=0.0045), tragal tenderness (P=0.0012) and congestion of tympanic membrane (P=0.0088) is statistically significant when comparing clotrimazole with povidone iodine. Apart from these, we did not reveal any adverse effects from the study populations treated with povidone iodine soaked gelfoam., Conclusion: Use of the povidone iodine soaked gelfoam at the external auditory canal in recalcitrant otomycosis is an effective and well-tolerated treatment., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Composites are attractive for its potential synergistic effects that can result in high-performance, but the synergy depends on subtle design. In this study, a hemostatic composite, a thrombin/cross-linked graphene sponge (TCGS), was developed through a facile gradient composite strategy. The porous structure of the CGS assures that the thrombin is stably embedded in the TCGS, avoiding a burst release but maintaining its bioactivity. In the synergy between proper thrombin stimulation and the fast absorption of the sponge, TCGS exhibits outstanding hemostatic performance, ultrafast bleeding cessation, within 100s, which is superior to both CGS and equal amounts of native thrombin. Lower or excessive thrombin dosages prolong the bleeding time. The study revealed that the balance between plasma absorption and thrombin stimulation at the interface is critical for improving hemostatic efficacy. TCGS is also highlighted for its biosafety and stability, even after 6 months of storage in environment. This potentially ultra-long shelf life is conducive to its practical applications. Therefore, TCGS not only provides a new strategy for developing a hemostatic composite but also provides a new method and understanding for the design of hemostatic materials., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.

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.

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., (Copyright © 2017 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.)

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.

Topical hemostatic agents are used intra-operatively to prevent uncontrolled bleeding. Gelfoam(®) Powder contains a hemostatic agent prepared from purified pork skin gelatin, the efficacy of which is increased when combined with thrombin. However, the effect of increasing concentrations of thrombin on resultant hemostasis is not known. This study sought to evaluate the ability of various concentrations of thrombin in combination with Gelfoam Powder to control bleeding using a swine liver lesion model. Ten pigs underwent a midline laparotomy. Circular lesions were created in the left medial, right medial, and left lateral lobes; six lesions per lobe. Gelfoam Powder was hydrated with Thrombin-JMI(®) diluted to 250, 375, and 770 IU/mL. Each concentration was applied to two lesion sites per lobe. Bleeding scores were measured at 3, 6, 9, and 12 min using a 6-point system; comparison of bleeding scores was performed using ANOVA with the post hoc Tukey test. The bleeding scores with thrombin concentrations at 770 IU/mL were significantly lower than at 250 and 375 IU/mL at all four time points. The percentage of biopsies with a clinically acceptable bleeding score rose from 37.9, 46.6, and 71.2 % at 3 min to 55.2, 69.0, and 88.1 % at 12 min in the 250, 375, and 770 IU/mL thrombin groups, respectively. The study showed that the hemostatic response to thrombin was dose-related: using higher concentrations of thrombin with Gelfoam Powder yielded improved hemostasis, as determined by lower bleeding scores., Competing Interests: Dennis Morse, Elif Silva, and David Potter are full-time employees of Pfizer and hold stock and/or stock options in Pfizer. Jolee Bartrom, Kelli Young, and Eric Bass are full-time employees of NAMSA and have no conflicts of interest to declare. Trevor Bieber is self-employed, owns no Pfizer stock/options, and has no other conflicts of interest to declare. Ethical approval All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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., (© 2016 S. Karger AG, Basel.)

Purpose: The major complications of partial nephrectomy are bleeding and urine leakage. While various hemostatic agents are used to control bleeding, the histopathological characteristics of these hemostatic agents have not been investigated adequately. We aimed to investigate and compare the histopathological and hemostatic effects of local hemostatic agents in a partial nephrectomy rat model., Methods: Thirty-two rats were divided into four equal groups, and partial nephrectomy was done to all rats. Conventional suture repair, Glubran2®, FloSeal®, and Celox™ were applied to every single group. The period of warm ischemia and hemostasis during surgical process was timed. Rats were killed later 3 weeks, and their partial nephrectomy applied kidneys were evaluated histopathologically., Results: The fastest hemostasis was provided with Glubran2® (32.87 s). FloSeal® was the second (40.85 s), and Celox™ was the third (55.75 s). Glomerular necrosis and calcification were seen more in the suture group than other groups (p < 0.001). Fibrosis was found significantly less in Celox™ group. Fibroblast activation was found significantly less comparing to other groups (p < 0.01). The erythrocyte aggregation was significantly greater in the Glubran2® and FloSeal® groups than suture group (p < 0.01 and p < 0.001)., Conclusion: The negative effects of hemostatic agents to the renal histopathology were less than conventional suture repair. Celox™ was the best biocompatible agent. In comparison with three agents, it was observed that Glubran2® provided hemostasis faster than other agents.

As absorbable hemostatic dressings, chitosan with a deacetylation degree of 40% (CS-40) and 73% (CS-73) have been fabricated into sponges via a modified method. The hemostatic, biocompatible and biodegradable properties were evaluated through in vivo assays. In a hepatic hemorrhage model, the chitosan sponges, with excellent blood compatibility, achieved less blood loss than the gelation sponge (GS). In addition, CS-40 showed better hemostatic capability and biodegradability than CS-73. After implantation, a histological analysis indicated that CS-40 exhibited the best biodegradability, tissue regeneration and least tissue adhesion. By contrasting CS-40 and CS-73, the deacetylation degree is confirmed to be a key factor for the hemostatic effect, biodegradability, biocompatibility and tissue regeneration. Our overall results demonstrated the potential application of CS-40 for use in absorbable hemostatic dressings., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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.

Objective: Treatment of vocal fold scarring remains challenging. We have previously reported the therapeutic effects of local injection of basic fibroblast growth factor (bFGF) in animal models and humans. A novel collagen/gelatin sponge (CGS) is capable of sustained release of bFGF, which compensates for its quick absorption in vivo, avoiding multiple injections. This study aimed to evaluate the biocompatibility and efficacy of the CGS in rat vocal fold fibroblasts prior to human trials., Methods: Fibroblasts extracted from Sprague-Dawley rat vocal folds were seeded onto a CGS and then cultivated with bFGF at concentrations of 0, 10, and 100 ng/mL. Vocal fold fibroblast morphology, adhesion, proliferation, and gene expression were measured under these 3-dimensional conditions., Results: Cells adhered to the CGS from day 1. Although no significant differences in cell morphology were detected, cell proliferation was accelerated by bFGF administration. Expression of endogenous bFGF and hepatocyte growth factor was significantly up-regulated at 10 ng/mL bFGF. The expression of procollagen I and procollagen III was significantly suppressed, whereas HAS-1 and HAS-2 were up-regulated at 10 and 100 ng/mL bFGF., Conclusion: The collagen/gelatin sponge is biocompatible with vocal fold fibroblasts and may be useful as a bFGF drug delivery system for the treatment of scarred vocal folds., (© The Author(s) 2014.)

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., (Copyright 2015, SLACK Incorporated.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

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.

Objective: The aim of this study is to compare the effects of the absorbable gelatin sponge (AGS), microporous polysaccharide hemospheres (MPH), and Ankaferd on wound healing after middle ear trauma and to evaluate their ototoxicity in an experimental guinea pig model., Methods: Middle ear mucosal trauma was created in 21 healthy adult guinea pigs. MPH, Ankaferd, and AGS were applied into the right tympanic bulla of the guinea pigs (7 ears for each treatment modality). The left ears of the seven animals were used as the sham group. At the fourth postoperative week (28-30 days), the guinea pigs were decapitated. Apoptosis was investigated, and the expression of Bcl-xl, Apaf, p53, cytochrome 3, and caspase 3 were evaluated., Results: The Ankaferd and AGS groups demonstrated significantly lower epithelial thickness, inflammation, and capillary dilatation than did the control group (p<0.001, <0.001, /0.001, <0.001/, 0.005, and 0.005, respectively). A statistically significant decrease in Bcl-xl staining was observed in the middle ears of animals treated with MPH (p=0.003). There was significantly higher caspase 3 expression in the Ankaferd and AGS groups than in the control group (p<0.001 and p=0.002, respectively)., Conclusion: Light microscopy indicates that Ankaferd and AGS create less inflammation and increased caspase expression, which seems to induce inflammatory cell apoptosis. Ankaferd seems to be a promising hemostatic agent in otology., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

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.

Background and Purpose: Absorbable gelatin-thrombin matrix is increasingly being used in neurosurgical procedures; unlike other hemostats, the stable matrix is left undisturbed and fills the surgical bed after achieving hemostasis. We investigated the immediate postoperative radiographic imaging appearance of the gelatin-thrombin matrix in intracranial operative beds., Materials and Methods: Thirty-one consecutive patients (18 men, 13 women; mean age, 59 years) with 34 surgical cavities, had 31 brain MRIs and 9 head CTs performed ≤ 48 hours postoperatively. They were retrospectively reviewed. Images were evaluated independently by 2 neuroradiologists blinded to the surgical techniques. Surgical beds were evaluated for the presence of the gelatin-thrombin matrix, which appeared as pseudoair material (Hounsfield units ≤ -100) on CT, had characteristic T2-hypointense speckles in a T2-hyperintense background, and demonstrated complete gradient-recalled echo hypointensity on MR imaging. To determine the diagnostic performance of imaging features for the detection of the gelatin-thrombin matrix, the Fisher exact test for the association between imaging features and the presence of the gelatin-thrombin matrix and κ analysis for interobserver agreement were performed., Results: Hemostasis was achieved with standard methods in 12 surgical beds and with the gelatin-thrombin matrix in 22 beds. Interobserver agreement was substantial. The gelatin-thrombin matrix demonstrated pseudoair hypoattenuation (88% sensitivity, 100% specificity, 90% accuracy; P = .067, κ = 0.74) and distinctive T2-hypointense speckles in a background of T2-hyperintensity (81% sensitivity, 85% specificity, 82% accuracy; P = <.001, κ = 0.76). Combined characteristic T2 speckles and gradient-recalled echo hypointensity increased the specificity (81% sensitivity, 100% specificity, 88% accuracy; P = < .001)., Conclusions: The unique appearance (pseudoair on CT, T2 speckles with gradient-recalled echo hypointensity) of the gelatin-thrombin matrix should not be mistaken for gossypiboma, pneumocephalus, and/or hematoma.

Fracture is one of the most life-threatening injuries in horses. Fracture repair is often associated with unsatisfactory outcomes and is associated with a high incidence of complications. This study aimed to evaluate the osteogenic effects of gelatin/β-tricalcium phosphate (GT) sponges loaded with different concentrations/ratios of mesenchymal stem cells (MSCs) and bone morphogenetic protein-2 (BMP-2) in an equine bone defect model. Seven thoroughbred horses were used in this study. Eight bone defects were created in the third metatarsal bones of each horse. Then, eight treatments, namely control, GT, GT/M-5, GT/M-6, GT/M-5/B-1, GT/M-5/B-3, GT/M-6/B-1, and GT/M-6/B-3 were applied to the eight different sites in a randomized manner (M-5: 2 × 10(5) MSCs; M-6: 2 × 10(6) MSCs; B-1: 1 μg of BMP-2; B-3: 3 μg of BMP-2). Repair of bone defects was assessed by radiography, quantitative computed tomography (QCT), and histopathological evaluation. Radiographic scores and CT values were significantly lower in the control group than in the other groups, while they were significantly higher in the GT/M-5/B-3 and GT/M-6/B-3 groups than in the other groups. The amount of mature compact bone filling the defects was greater in the GT/M-5/B-3 and GT/M-6/B-3 groups than in the other groups. The present study demonstrated that the GT sponge loaded with MSCs and BMP-2 promoted bone regeneration in an equine bone defect model. The GT/MSC/BMP-2 described here may be useful for treating horses with bone injuries.

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., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the safety and the delivery function of cisplatin-conjugated-soluble gelatin sponge in a swine model., Methods: Fifteen healthy young swine were assigned into three groups: transarterial cisplatin infusion group, transarterial chemoembolization (TACE) with cisplatin-conjugated 120-min soluble gelatin sponge (TACE-120) group, and TACE with cisplatin-conjugated 360-min soluble gelatin sponge (TACE-360) group. A total volume of 0.8 mL/kg cisplatin in each group and 8 mg/kg soluble gelatin sponge in TACE-120 and TACE-360 groups were injected from the left hepatic artery in small increments for 10 min. Common hepatic angiography and whole-blood sampling via the left hepatic vein were conducted to explore recanalization immediately after the procedure and again at 10, 30, 60, 90, 120, 180, 240, 300, 360, and 420 min later. The area under the plasma concentration curve (AUC) of non-protein-bound platinum was compared among the three groups. Each liver was removed and cut into 10-cm-thick sections for calculating liver-damaged volume ratio., Results: Sequential angiography depicted gradual recanalization of the occluded hepatic artery and total recanalization at 120 and 360 min after embolization in the TACE-120 and TACE-360 groups, respectively. Of the three groups, AUC(0-30), AUC(30-120), and AUC(120-420) were significantly highest in the transarterial cisplatin infusion group (p < 0.001), the TACE-120 group (p < 0.001), and the TACE-360 group (p < 0.001), respectively. The liver-damaged volume ratio in the TACE-360 group was small (8.20 %) but significantly higher than that in the TACE-120 group (2.67%, p = 0.014)., Conclusion: Cisplatin-conjugated soluble gelatin sponge functions as a cisplatin carrier and is associated with tolerable liver damage.

Background: Bioresorbable porous substrates from copolymers have their application in tissue engineering to culture tissues in vitro. The advantage of polymers is the production of thermoplastic elements and their ability to biodegrade in a living body. Gelatin, collagen, alginates are part of dressings used for topical administration of the drug. Research was undertaken to achieve a porous gelatin-alginate matrix which could be used in therapy as among others, a carrier for a drug., Objectives: Evaluation of the impact of modified gelatin-alginate matrix on activation of plasma coagulation in vivo., Material and Methods: Gelatin-alginate matrix cross-linked with calcium ions was implanted in the muscle tissue of a rat. The control group constituted animals not implanted with material, but they passed the operating procedure. Blood samples of plasma coagulation test and control group were collected after 1, 2, 3, 5, 7, 10, 14 days of the procedure., Results: Prolongation of APTT and shortening of PT and TT with the unchanged values of fibrinogen and the count of platelet cells was observed till the 5th day on the basis of the obtained results. Prolongation of APTT with the unchanged values of the remaining parameters of the coagulation system was observed after 7, 10 and 14 days with unchanged values of PT and TT coagulation., Conclusions: The matrix gelatin-alginate with calcium ions in the biological environment undergoes biodegradation in soft tissues. This process in the initial period influences the activation of the coagulation within the intrinsic and extrinsic system. From the 5th to 14th day the activation of coagulation was observed only in the intrinsic system.

Background: Knowledge of the relation of biomaterials and living tissues constitutes necessary information which should be used when composing a set of optimal carriers, e.g. for drugs or preparations supporting blood clotting., Objectives: This paper presents an assessment of the influence of contact of gelatin-alginian matrixes with blood on leukocyte reactivity: the ability of mononuclear cells (lymphocytes and monocytes) to create a radial segmentation of nuclei--RS (the morphological change), and the ability of leukocytes to phagocytosis of yeast Saccharomyces cerevisiae cells and to produce active oxygen derivatives (functional changes)., Material and Methods: After having contact with the matrixes, the test of induced and spontaneous RS, the phagocytic test and nitroblue tetrazolium reduction test for blood leukocytes were performed., Results: The obtained results showed a decrease in the ability of mononuclear cells to form RS and in the ability of granulocytes to reduce nitroblue tetrazolium--NBT, but an increase in their phagocytic activity., Conclusions: Temporary contact of gelatin-alginian matrixes with blood did not cause any morphological changes in the leukocytes. However, changes of their reactivity were observed.

Objective: To compare the bleeding time using 3 different hemostatic agents in a rat model of partial nephrectomy and aortic needle injury., Methods: Bilateral partial nephrectomy was performed in 20 rats with a total bleeding surface of 1.5 cm(2) without vascular clamping. Surgicel (n = 10) or BloodSTOP iX (n = 10) matrix was applied on each kidney cut surface. Finger pressure was applied to the parenchyma with transparent plastic bubble wrap to allow for visualization of the site and monitor the bleeding time. Pressure was applied until the bleeding stopped and then released to assess the presence of active bleeding for 5 minutes. An additional 24 rats underwent aortic trauma with a 25-gauge needle puncture, and the efficacy of the topical hemostatic agents were compared among Gelfoam (n = 8), Surgicel (n = 8), and BloodSTOP iX (n = 8)., Results: After partial nephrectomy, the mean bleeding time with BloodSTOP iX and Surgicel treatment was 83.70 ± 13.73 seconds and 168.8 ± 19.41 seconds, respectively, a statistically significant difference (P = .002). After aortic injury, the mean bleeding time was 157.5 ± 31.44 seconds, 187.5 ± 23.20 seconds, and 66.00 ± 13.74 seconds in the Gelfoam, Surgicel, and BloodSTOP groups, respectively, which was statistically significant (P = .004)., Conclusion: The BloodSTOP iX hemostatic surgical matrix was more effective in reducing the bleeding time than Surgicel in a rat model of partial nephrectomy. Similarly, in an aortic needle injury model, BloodSTOP iX achieved hemostasis faster than Gelfoam or Surgicel., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Bone marrow mesenchymal stem cells (MSCs) have been used for bone tissue engineering due to their osteogenic differentiation capability, but their application is controversial. To enhance their capability, we prepared biodegradable gelatin sponges incorporating β-tricalcium phosphate ceramics (GT sponge), which has been shown to possess excellent controlled drug-release properties. The GT sponge was used as a carrier for both rat MSCs and bone morphogenetic protein-2 (BMP-2) and osteogenic differentiation was assessed by subcutaneous implantation of four different kinds of implants, i.e. GT-alone, MSC-GT composites, BMP-GT composites and BMP-GT composites supplemented with MSCs (BMP-MSC-GT) in rats. Two weeks after implantation, histological sections showed new bone formation in the peripheral parts of the BMP-GT and in almost the total volume of the BMP-MSC-GT implants. After 4 weeks, histology as well as microCT analyses demonstrated extensive bone formation in BMP-MSC-GT implants. Gene expression and biochemical analyses of both alkaline phosphatase and bone-specific osteocalcin confirmed the histological findings. These results indicate that the combination of MSCs, GT and BMP synergistically enhances osteogenic capability and provides a rational basis for their clinical application in bone reconstruction., (Copyright © 2011 John Wiley & Sons, Ltd.)

To treat large bone defects is a clinically challenging problem and utilizing tissue engineering technology is an attractive approach for overcoming such a problem. Previously, a biodegradable sponge incorporating bone morphogenic protein-2 (BMP-2), which can control the release of BMP-2 for a prolonged time in an in vivo environment, was reported. In addition, a biodegradable sponge composed of gelatin and β-tricalcium phosphate (βTCP), gelatin-βTCP sponge to develop a more ideal scaffold for enhancing bone regeneration was also created and previously reported. The purpose of this study was to investigate the effectiveness of the gelatin-βTCP sponge for the promotion of bone regeneration in a critical-sized bone defect site in vivo. Apparent bone regeneration was induced by the gelatin sponge incorporating BMP-2 and the gelatin-βTCP sponge with BMP-2 incorporation. In contrast, no apparent bone formation was induced by either the gelatin sponge only or the gelatin-βTCP sponge without BMP-2. To investigate the quality of the regenerated bone, we conducted a biomechanical evaluation with a three-point bending test. We found no significant difference between the gelatin sponge incorporating BMP-2 and the gelatin-βTCP sponge incorporating BMP-2 groups. Incorporation of βTCP into the gelatin sponge was expected to enhance biomechanical strength during the initial bone regeneration. However, our observations showed that the gelatin-βTCP sponge did not significantly improve the quality of regenerated bone from the viewpoint of biomechanical assessment, even though it did not impair the effectiveness of the promotion of bone regeneration by BMP-2 in the bone defect., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: Administration of a recombinant peptide of Periostin (rPN) has recently been shown to stimulate cardiomyocyte proliferation and angiogenesis after myocardial infarction (MI) [1]. However, strategies for targeting the delivery of rPN to the heart are lacking. Intrapericardial administration of drug-eluting hydrogels may provide a clinically viable strategy for increasing myocardial retention, therapeutic efficacy, and bioactivity of rPN and to decrease systemic re-circulation., Methods and Results: We investigated the ability of intrapericardial injections of drug-eluting hydrogels to deliver and prolong the release of rPN to the myocardium in a large animal model of myocardial infarction. Gelfoam is an FDA-approved hemostatic material commonly used in surgery, and is known to stimulate fibrin clot formation. We show that Gelfoam disks loaded with rPN, when implanted within the pericardium or peritoneum of mammals becomes encapsulated within a non-fibrotic fibrin-rich hydrogel, prolonging the in vitro and in vivo release of rPN. Administration into the pericardial cavity of pigs, following a complete occlusion of the left anterior descending artery, leads to greater induction of cardiomyocyte mitosis, increased cardiomyocyte cell cycle activity, and enhanced angiogenesis compared to direct injection of rPN alone., Conclusions: The results of this study suggest that intrapericardial drug delivery of Gelfoam, enhanced by triggered clot formation, can be used to effectively deliver rPN to the myocardium in a clinically relevant model of myocardial infarction. The work presented here should enhance the translational potential of pharmaceutical-based strategies that must be targeted to the myocardium.

Background and Purpose: Laparoscopic partial nephrectomy (LPN) paralleling open techniques, particularly closure of the collecting system, can be technically challenging for the novice laparoscopist. We describe operative results and complications of a single surgeon, retrospectively reviewed series using a simplified method of hand assistance and a fibrin glue patch for hemostasis without formal collecting system closure., Patients and Methods: We identified 104 consecutive patients between September 2003 and January 2009 who underwent hand-assisted laparoscopic partial nephrectomy (HALPN). Our technique involves routine hilar clamping after isolation of the tumor and mobilization of the kidney. After resection of the mass, a fibrin glue patch is placed within the surgical defect and secured with bolstering sutures. No attempt is made to suture the collecting system, nor are ureteral catheters placed when the collecting system is entered during resection of the tumor., Results: Mean tumor size was 2.8 cm (median 2.5 cm, range 0.7-7.0 cm). With hilar clamping, warm ischemia time averaged 24.5 minutes (range 11-39 min). Estimated blood loss averaged 220 mL (range 50-1500 mL), and five (4.8%) patients received transfusions either intraoperatively or postoperatively. Urine leak occurred in 1.9% (n=2) of patients overall and 4.3% (2/47) of patients with documented collecting system entry. Both urine leaks resolved with conservative management only., Conclusions: HALPN without formal collecting system closure is a safe and effective technique with similar urine leak and transfusion rates compared with other series. This technique may allow more urologists to perform minimally invasive partial nephrectomy or to do so with potentially shorter ischemia times.

This study was designed to evaluate the effect of autologous bone marrow mesenchymal stem cells (MSCs) seeded into Gelfoam® on structural bone allograft healing. Thirty New Zealand white rabbits were divided into two groups. Segmental bone defect was created on diaphysis of the femur, and the defect was reconstructed with structural bone allograft. In experimental group, structural allograft was wrapped around by Gelfoam® containing autologous MSCs, whereas cells were not included in control group. At 4, 8, 12 weeks, the femur of rabbits underwent radiographic and histologic evaluation for bony union. Bone morphogenic protein-2 (BMP-2), BMP-4, BMP-7, vascular endothelial growth factor (VEGF), and receptor activator of nuclear factor-kappa B ligand (RANKL) were measured within the grafted periosteal tissue. Bony union was not achieved in both groups at 4 and 8 weeks. At 12 weeks, three out of five femurs in experimental group were united, but one out of five in control group was united. Mean Taira scores were significantly different between two groups. The expression of BMP-2 was significantly higher at 4, 8 weeks, the expressions of BMP-4 and BMP-7 were significantly higher at 8 and 12 weeks, and the expression of VEGF and RANKL were significantly higher at all time points in experimental group. Incorporation of the structural bone allograft could be enhanced if allograft is covered with Gelfoam® containing autologous MSCs. MSCs have influence on not only bone formation, but neo-angiogenesis, and bone resorption.

Purpose: To evaluate the efficacy and cost-effectiveness of FloSeal(®) hemostatic matrix in preventing lymphocele development after pelvic lymphadenectomy (PLA)., Materials and Methods: This was a single-center, matched comparison of lymphadenectomies in laparoscopic and robot-assisted extraperitoneal radical prostatectomy (ERP) performed with and without FloSeal between January 2008 and October 2009. FloSeal was applied topically in the lymphadenectomy zone immediately after node resection. Cost analysis for lymphocele treatment was performed., Results: A total of 142 patients underwent PLA with ERP (32 with FloSeal, 110 without FloSeal). The mean number of lymph nodes removed was 6.5±4.5 (range 2-20). Median prostate-specific antigen concentration was 8.5  ng/mL (range 1.5-24  ng/mL). There was one (3.1%) symptomatic lymphocele in the FloSeal group compared with 16 (14.5%) in the non-FloSeal group. The median number of lymph nodes removed was 8 (range 5-20) in the FloSeal group and seven (range 3-25) in the non-FloSeal group. The only lymphocele in the FloSeal group was treated with percutaneous drainage alone. In the non-FloSeal group, six symptomatic lymphoceles were managed conservatively-four with percutaneous puncture and six with fenestration after percutaneous drainage. The mean cost per patient of treating symptomatic lymphoceles was €327 ($455) in the FloSeal group (total costs €10,481 [$14,559]) vs €553 ($769) (total costs €60,870 [$84,551]) in the non-FloSeal group., Conclusions: These preliminary data suggest that the use of FloSeal after lymphadenectomy can reduce the number of symptomatic lymphoceles and is cost-effective.

To prepare a soluble gelatin sponge (GS) and to explore the GS particles (GSPs) that inhibit development of collateral pathways when transcatheter hepatic arterial embolization is performed. The approval of the Institutional Committee on Research Animal Care of our institution was obtained. By means of 50 and 100 kDa of regenerative medicine-gelatin (RM-G), RM-G sponges were prepared by freeze-drying and heating to temperatures of 110-150°C for cross-linkage. The soluble times of RM-GSPs were measured in vitro. Eight swine for transcatheter hepatic arterial embolization were assigned into two groups: six received 135°C/50RM-GSPs, 125°C/100RM-GSPs, and 138°C/50RM-GSPs, with soluble time of 48 h or more in vitro; two swine received Gelpart GSPs (G-GSPs) with insoluble time of 14 days as a control. Transarterial chemoembolization was performed on two branches of the hepatic artery per swine. RM-GSPs heated at temperatures of 110-138°C were soluble. Mean soluble times of the RM-GSPs increased with higher temperature. Hepatic branches embolized with G-GSP remained occluded after 6 days, and development of collateral pathways was observed after 3 days. Hepatic branches embolized with 135°C/50RM-GSP and 125°C/100RM-GSP remained occluded for 4 h, and recanalization was observed after 1 day. Hepatic branches embolized with 138°C/50RM-GS remained occluded for 1 day, and recanalization was observed after 2 days with no development of collateral pathways. In RM-GSs with various soluble times that were prepared by modulating the heating temperature, 138°C/50RM-GSP was the soluble GSP with the longest occlusion time without inducing development of collateral pathways.

This study was designed to compare the efficacy of transcatheter arterial embolization (TAE) with N-butyl cyanoacrylate (NBCA) or gelatin sponge particles (GSP) for acute arterial bleeding in a coagulopathic condition using a swine model. Four healthy swine were divided into two coagulopathic conditions: mild and severe. Five hemorrhages were created in each swine (10 hemorrhages per coagulopathy). Mild coagulopathy was achieved by bloodletting 10% of the total circulatory whole blood and preserving activated clotting time (ACT) less than 200 s (ACT < 200 s state); severe coagulopathy was achieved by bloodletting 30% and preserving ACT > 400 s (ACT > 400-second state). For each state, of ACT < 200 s or ACT > 400 s, TAE was conducted with GSP or NBCA to control five hemorrhages arising from artificially created renal and splenic injuries. Angiography immediately after TAE with GSP or NBCA showed complete occlusion in both coagulopathic conditions. In the ACT < 200-second state, follow-up angiography at 5-30 min after TAE with GSP or NBCA showed no evidence of recurrent hemorrhage. In the ACT > 400-second state, follow-up angiography showed recurrent hemorrhage in four (80%) of the five hemorrhages embolized with GSP and in one (20%) of the five hemorrhages embolized with NBCA. Microscopically, red thrombi were observed densely surrounding GSP in mild coagulopathy but were scarce in severe coagulopathy. In a condition with severe coagulopathy, TAE with NBCA was more effective in durability to cease active arterial bleeding than with GSP.

This paper reviews the mechanisms and properties of different absorbable hemostatic agents. The development tendency of absorbable hemostatic agent is forecasted. Its' qualities of being useful to surgeons are introduced and are embodied in surgeon's comprehending of the hemostatic characteristic of absorbable hemostatic agents as well as in their clinical use of such agents accurately. At the same time, the researchers in pursuit of the medical materials can work with reference to the data herein presented.

Background: Management of post-operative bleeding has historically used topical bovine thrombin. However, possible harm through activation of coagulation inhibitors has encouraged investigation with other hemostatic agents. This study utilized a novel ordinal bleeding model to test whether a Gelfoam + human thrombin solution is superior at controlling bleeding when compared to Gelfoam + saline solution at different time intervals., Study Design: Four swine underwent open laparotomy after receiving unfractionated heparin. Twenty open liver biopsies were performed in each swine; ten biopsies treated with Gelfoam + human thrombin solution and 10 biopsies treated with Gelfoam + saline solution. Three, 6 min, and 12 min after the procedure, bleeding was objectively graded by a four-point model., Results: There was a significant (P < 0.017), treatment effect on each success/failure outcome (success = bleeding score 1) at 3 (P < 0.001), 6 (P < 0.001), and 12 (P = 0.003) min, based on a 2 x 2 Fisher's exact test. Similarly, there was a significant treatment effect on each success/failure outcome and four-point bleeding score based on a multiple logistic regression analysis controlling for pig, lesion weight, and initial bleeding taking into consideration repeated measures at three time points., Conclusions: The results demonstrate a superior treatment effect for control of bleeding using human thrombin compared to a saline solution. Future studies should compare bovine thrombin versus human thrombins ability to control bleeding as well as the hazard of each in activating coagulation inhibitors.

Background and Purpose: An increased amount of fibrosis formed after lumbar surgery may be the underlying cause of the failed back surgery syndrome in most cases. Various materials have been used to prevent epidural fibrosis, but only limited success has been achieved. In this study, the authors investigated the effect of FloSeal (a gelatine-containing thrombin-based haemostatic agent) on spinal epidural fibrosis in a rat laminectomy model., Material and Methods: Sixteen Wistar rats underwent laminectomy at L4 and L5 levels. In 8 rats, 0.5 mL of FloSeal was locally applied to the laminectomy site. The laminectomy site was irrigated with saline in the control group of 8 other rats. The rats were sacrificed four weeks later. Each specimen was examined for density of fibrosis, and both fibroblast and inflammatory cell density., Results: Epidural fibrosis density differed significantly between the FloSeal group and the control group. Evaluation of the fibroblast density and the inflammatory cell density showed a statistically significant difference between the FloSeal group and the control group., Conclusion: Application of FloSeal at a laminectomy site may be useful to decrease adhesion at the interface between the dura mater and epidural fibrosis.

Objective: To investigate histologic changes in the mucosa of rat middle ear after implantation of three different support materials., Study Design: A prospective, controlled animal study., Subjects and Methods: Three types of absorbable materials were implanted into the middle ear cavity of rats: (1) Gelfoam (purified gelatin) (Pharmacia & Upjohn Company, New York, NY), (2) Sepragel (viscoelastic gel composed of cross-linked polymers of hyaluronan) (GENZYME Corp, Ridgefield, NJ), and (3) Nasopore (a biodegradable/fragmentable, synthetic polyurethane foam) (Polyganics, Groningen, The Netherlands). Rats were sacrificed after 3 and 20 days to ascertain early and late histologic changes. The bulla of each rat was excised and prepared for microscopic examination. The histologic changes were evaluated by observation of the middle ear cavity and mucosa in terms of polymorphonuclear leucocytes (PMNL), macrophages, giant cells, fibroblasts and other cells, fibrosis, and remnant materials., Results: The histologic appearance of gelfoam-treated middle ears was characterized by more severe acute inflammation in the short-term and prominent fibrosis in the long-term in comparison with sepragel- and nasopore-treated groups. Nasopore appeared to be prone to remnant formation and reorganization by means of fibroblastic activity., Conclusion: Compared with gelfoam, both sepragel and nasopore caused less histologic alterations.

Background & Objective: The presence of adhesions after middle ear surgery is not uncommon. Fibrosis can cause conductive hearing loss and it contributes to retraction of the tympanic membrane in the post-surgery patient. The purpose of this study was to evaluate the anti-adhesive effect of Seprafilm and MeroGel in the abraded mucosa of a guinea pig's middle ear., Materials and Methods: Fifteen pathogen-free adult male albino guinea pigs weighing 250-300g each were used. Under an aseptic condition, the middle ear mucosa was abraded using a pick through a myringotomy incision. Seprafilm, MeroGel and Gelfoam, respectively, were then packed into guinea pigs' middle ear cavities. Auditory brainstem responses (ABRs) were assessed preoperatively and 3 weeks after operation., Results: The ABR results at postoperative week 3 showed no statistically significant difference for the myringotomy and postpacking, except for the MeroGel packing. However, there was no significant threshold on the 6 weeks' postoperative ABR. The Gelfoam group demonstrated extensive fibrosis and adhesion within the bulla cavity. The Seprafilm and MeroGel groups showed no adhesion in the middle ear cleft after abrasion of the mucosa., Conclusion: From these results, we suggest the use of Seprafilm and MeroGel to improve the results of otosurgery.

Objectives: The aim of the study was to evaluate the effects and morbidities of Meropack, an absorbable hyaluronic acid packing material, placed in the middle meatus after endoscopic sinus surgery in children with chronic sinusitis., Methods: Sixty consecutive children with similar degrees of bilateral chronic sinusitis were enrolled in the study. Meropack was randomly inserted into one side of the middle meatus, while the opposite sinus was not packed after functional endoscopic sinus surgery. Patients were investigated 3, 8, and 12 weeks after surgery. The effects and morbidities of nasal dressings in the middle meatus were evaluated with respect to six distinct parameters: blood loss during surgery, postoperative hemorrhage, synechiae, granulation tissue, infection, and patency of the maxillary sinus ostia., Results: Mean blood loss of packed and unpacked sinuses did not significantly differ (p > 0.05). Twenty-nine (15 packed, 14 unpacked) of the 120 sinuses underwent resection of the lateral wall of concha bullosa. Four of 14 unpacked sinuses had postoperative hemorrhaging, while the 15 packed sinuses did not (p < 0.05). The mean synechiae scores at the first follow-up visit for the Meropack filled and unpacked sinuses differed significantly (p < 0.05). For the 8- and 12-week follow-up visits, severity of adhesions, granulation tissue formation, infection rate, and patency of the maxillary sinus ostia did not differ significantly between the Meropack filled sinuses and the unpacked sinuses (p > 0.05 for all)., Conclusion: Meropack dressings effectively prevented postoperative hemorrhage, but did not significantly reduced synechiae after endoscopic sinus surgery. Therefore, we recommend that Meropack packing is not necessary for routine use following pediatric functional endoscopic sinus surgery (FESS). However, it should be reserved for children who are predisposed to develop postoperative hemorrhages or adhesions, such as resection of the concha bullosa, traumatic surgery with the creation of large raw surfaces on the middle turbinate, and revision surgery with preexisting adhesions.

Objectives/hypothesis: Absorbable hemostatic agents are used routinely following sinus surgery. Recent studies suggest that current biomaterials, such as FloSeal Matrix Hemostatic Sealant (Fusion Medical Technologies, Mountain View, CA) may interfere with mucosal regeneration. This study was designed to evaluate the effects of Microporous Polysaccharide Hemospheres (MPH, Medafor, Inc., Minneapolis, MN), a novel rapidly-absorbing hemostatic powder, on healing and intact sinus mucosa., Study Design: Prospective, controlled study using the rabbit model., Methods: Both maxillary sinuses of 14 New Zealand white rabbits were surgically opened. The mucosa of 10 rabbits were stripped bilaterally, and the left sinus of each was then treated with either MPH or FloSeal. The mucosa of four additional rabbits were incised but otherwise remained undisturbed. Again, the left sinus of each of the four additional rabbits was treated with either MPH or FloSeal. The right sinus served as an untreated control (stripped or intact) in both arms of the study. Animals were recovered and euthanized 2 weeks later. Specimens were examined by a blinded pathologist using light microscopy., Results: Untreated regenerated mucosa showed expected areas of sparse cilia, mild serous gland reduction, and fibrosis. MPH-treated sinuses showed no significant changes compared to respective controls, and no MPH substance was identified. In contrast, regenerating mucosa treated with FloSeal showed extensive loss of cilia, inflammation, and fibrosis. Residual FloSeal particles were present within the sinus cavity and grossly incorporated within healing mucosa. Unexpectedly, intact mucosa exposed to FloSeal showed similar findings., Conclusions: Absorbable hemostatic materials have starkly different effects on mucosal healing. Unlike other agents, MPH is rapidly cleared and has no negative effects on healing or intact sinus mucosa.