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Oral infectious diseases may lead to bone loss, which makes it difficult to achieve satisfactory restoration. The rise of multidrug resistant bacteria has put forward severe challenges to the use of antibiotics. Silver (Ag) has long been known as a strong antibacterial agent. In clinic, gelatin sponge with colloid silver is used to reduce tooth extraction complication. To investigate how this material affect infected bone defects, methicillin-resistant Staphylococcus aureus (MRSA) infected 3-mm-diameter cranial defects were created in adult female Sprague-Dawley rats. One week after infection, the defects were debrided of all nonviable tissue and then implanted with gelatin sponge with colloid silver (gelatin/Ag group) or gelatin alone (gelatin group). At 2 and 3 days after debridement, significantly lower mRNA expression levels of IL-6 and TNF-α and lower plate colony count value were detected in gelatin/Ag group than control. Micro-CT analysis showed a significant increase of newly formed bone volume fraction (BV/TV) in gelatin/Ag treated defects. The HE stained cranium sections also showed a faster rate of defect closure in gelatin/Ag group than control. These findings demonstrated that gelatin sponge with colloid silver can effectively reduce the infection caused by MRSA in cranial defects and accelerate bone healing process. [ABSTRACT FROM AUTHOR]

The objective of this study is to design a drug delivery system (DDS) for the in vivo promotion of macrophage recruitment. As the drug, a water-insoluble agonist of sphingosine-1-phosphate type 1 receptor (SEW2871) was selected. SEW2871 (SEW) was water-solubilized by micelle formation with gelatin grafted by l -lactic acid oligomer. SEW micelles were mixed with gelatin, followed by dehydrothermal crosslinking of gelatin to obtain gelatin hydrogels incorporating SEW micelles. SEW was released from the hydrogels incorporating SEW micelles in vitro and in vivo. The water-solubilized SEW showed in vitro macrophage migration activity. When implanted into the back subcutis or the skin wound defect of mice, the hydrogel incorporating SEW micelles promoted macrophage migration toward the tissue around the implanted site to a significantly great extent compared with SEW-free hydrogel and that mixed with SEW micelles. The hydrogel is a promising DDS to enhance macrophage recruitment in vivo. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate a thin gelatin hydrogel membrane containing p-tricalcium phosphate (G-TCP) for use in guided bone regeneration, a technique that we developed. G-TCP membranes were fabricated from gelatin and β-TCP powder, freeze-dried, and cross-linked by heating. The resulting G-TCP membranes were as thin as collagen membranes, with high mechanical integrity. Proliferation and differentiation of rat bone marrow stromal cells (BMSCs) on G-TCP and collagen membranes were examined. On both membranes, BMSCs proliferated well and expressed alkaline phosphatase. However, more bone-like mineralized tissue formed on G-TCP membranes than on collagen membranes at 4 weeks. The effects of G-TCP and collagen membranes on bone regeneration in rat parietal bone defects were histologically examined. Bone bridges with mature uniform bone were observed under G-TCP membranes as early as 2 weeks. These results indicate that G-TCP is a GBR membrane that is comparable or superior to collagen membrane. [ABSTRACT FROM AUTHOR]

The objective of this study is to design biodegradable hydrogels for the controlled release of deferoxiamine (DFO) and evaluate their biological activity. When the DFO was added to human umbilical vein endothelial cells cultured in 5.0% O2, the level of hypoxia-inducible factor-1α and vascular endothelial growth factor significantly increased compared with that without DFO. The expression of angiogenesis-related genes was accordingly increased by the DFO addition. An aqueous solution of mixed gelatin and DFO was freeze-dried, and dehydrothermally treated at 140°C for 24h to prepare a gelatin hydrogel incorporating DFO. In the release test with phosphate-buffered saline solution (PBS) at 37°C, an initial DFO release of 60% was observed, followed by no release. When placed in PBS containing collagenase, the hydrogel was enzymatically degraded with time, and consequently released DFO in a degradation-dependent manner. After the hydrogel incorporating DFO was injected intramuscularly into a mouse model of hind limb ischemia, the number of new blood vessels formed was significantly higher than that with free DFO and DFO-free hydrogel. It is concluded that the DFO-containing hydrogel shows promising for inducing angiogenesis locally. [ABSTRACT FROM AUTHOR]

We prepared uncleaved gelatin composed mainly of collagen α-, β-, and γ-chains. Gelation and melting of uncleaved gelatin occurred rapidly with moderate decrease and increase in temperature (23°C–37°C). The viability of cells encapsulated in the gelatin gel was greater than 96% after 7 d at 23°C. [ABSTRACT FROM AUTHOR]

Abstract: The anticancer drug cisplatin was encapsulated within the cucurbit[7]uril macrocycle to form the host-guest complex: cisplatin@CB[7]. This was then incorporated into gelatin and 0–4% w/v polyvinyl alcohol (PVA)-based hydrogels as slow release drug delivery vehicles. The hydrogels demonstrated predicable swelling and disintegration dependent on the PVA concentration. The hydrogel with the highest PVA content was slower to swell and release drug compared with lower concentrations of PVA. The effect of the hydrogel PVA concentration on in vitro cytotoxicity was examined using A2780/CP70 ovarian cancer cells. Over the 24h drug exposure time used, hydrogels containing 4% PVA showed a 20% decrease in viable cells compared to the control, whereas hydrogels containing 0% and 2% PVA induced an 80% and 45% inhibition of cell growth, respectively. There was no measurable difference in the in vitro cytotoxicity of free cisplatin and cisplatin@CB[7] containing hydrogels. Finally, the in vivo effectiveness of a 2%-PVA hydrogel implanted under the skin of nude mice bearing A2780/CP70 xenografts showed that low dose hydrogels containing cisplatin@CB[7] (30μg equivalent of drug) was just as effective as an intraperitoneal high dose administration of free cisplatin (150μg) at inhibiting tumour growth. [Copyright &y& Elsevier]

Gelatin (Gel), sodium alginate (SA) and hyaluronic acid (HA) based various hydrogels for biomedical applications were prepared by freezing-drying method using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) as a crosslinker. The physical properties including morphology, water vapor transmission rate and hydrophilicity were investigated. The result showed the Gel/SA/HA composite hydrogels were successfully crosslinked by the crosslinking agent. All the Gel/SA/HA composite hydrogels with different compositions had highly homogeneous and interconnected pores, and the compositions had no significant effect on the surface and cross-section morphologies of the Gel/SA/HA hydrogels. The incorporation of sodium alginate enhanced the water vapor transmission capacity of the hydrogel; however, there were no significant differences between the water vapor transmission rates of all the Gel/SA/HA hydrogels. Gelatin had a low hydrophilic behavior, while sodium alginate exhibited relatively high hydrophilic behavior. The results indicate that the Gel/SA/HA hydrogel cross-linked via EDC is a potential wound dressing material capable of the adequate provision of moist environment for comfortable wound healing. [ABSTRACT FROM PUBLISHER]

Abstract: Macroporous elastic scaffolds containing gelatin (4% or 10%) and 0.25% hyaluronic acid (HA) were fabricated by cryogelation for application in adipose tissue engineering. These cryogels have interconnected pores (∼200μm), high porosity (>90%) and a high degree of cross-linking (>99%). The higher gelatin concentration reduced the pore size, porosity and swelling ratio of the cryogel but improved its swelling kinetics. Compressive mechanical testing of cryogel samples demonstrated non-linear stress–strain behavior and hysteresis loops during loading–unloading cycles, but total recovery from large strains. The presence of more gelatin increased the elastic modulus, toughness and storage modulus and yielded a cryogel that was highly elastic, with a loss tangent equal to 0.03. Porcine adipose-derived stem cells (ADSCs) were seeded in the cryogel scaffolds to assess their proliferation and differentiation. In vitro studies demonstrated a good proliferation rate and the adipogenic differentiation of the ADSCs in the cryogel scaffolds, as shown by their morphological change from a fibroblast-like shape to a spherical shape, decreased actin cytoskeleton content, growth arrest, secretion of the adipogenesis marker protein leptin, Oil Red O staining for triglycerides and expression of early (LPL and PPARγ) and late (aP2 and leptin) adipogenic marker genes. In vivo studies of ADSCs/cryogel constructs implanted in nude mice and pigs demonstrated adipose tissue and new capillary formation, the expression of PPARγ, leptin and CD31 in immunostained explants, and the continued expression of adipocyte-specific genes. Both the in vitro and in vivo studies indicated that the gelatin/HA cryogel provided a structural and chemical environment that enabled cell attachment and proliferation and supported the biological functions and adipogenesis of the ADSCs. [Copyright &y& Elsevier]

Abstract: The effect of different preparation parameters were analyzed with respect to the rheological and pharmaceutical characteristics of hydrogel blend patches, as transdermal delivery formulation. Mixtures of pectin and gelatin were employed for the production of patches, with adjustable properties, following a two-step gelation procedure. The first gelation, a thermal one, is trigged by the presence of gelatin, whereas, the second gelation, an ionic one, is due to the formation of the typical egg box structure of pectin. In particular, the patch structural properties were assessed by oscillation stress sweep measurements which provided information concerning their viscolelastic properties. In addition, different modalities for drug loading were analyzed with respect to drug homogeneous distribution; testosterone was employed as model drug for transdermal administration. Finally, the performances of the produced transdermal patches were studied, in term of reproducibility and reliability, by determination of in vitro drug release profiles. [Copyright &y& Elsevier]

Purpose: Hydrogel composites of oligo(poly(ethylene glycol) fumarate) (OPF) and gelatin microparticles (GMs) were investigated as carriers of bone morphogenetic protein-2 (BMP-2) for bone tissue engineering applications. Methods: Hydrogel composites with different physical characteristics were prepared by changing the amount and type (acidic vs. basic) of gelatin incorporated in the OPF bulk phase. Composites with differing physical properties (degradation, swelling, and mechanical properties) and differing BMP-2 loading phase were investigated to determine the effect of these factors on BMP-2 release profiles over 28 days. Results: Overall, higher gelatin amount increased the degradation and swelling of composites, and acidic GMs further increased the degradation and swelling and reduced the compressive modulus of the composites. The most significant factor affecting the release of BMP-2 from composites was the loading phase of the growth factor: GM loading reduced the burst release, increased BMP-2 release during the later phases of the experiment, and increased the cumulative release in faster degrading samples. Conclusions: The results indicate that the physical properties and the BMP-2 release kinetics of hydrogel composites can be controlled by adjusting multiple parameters at the time of the hydrogel composite fabrication. [ABSTRACT FROM AUTHOR]

Abstract: During the process of bone regeneration, a multitude of morphogenetic signaling factors regulate cellular behavior and ultimately tissue response. These factors are presented to cells under strong spatial and temporal control, which stresses the relevance of controlled delivery of multiple growth factors for bone tissue regeneration. This demand for biomimetic delivery has prompted the development of a novel generation of biomaterials that is capable of delivering multiple growth factors in a controlled manner. Therefore, the current study has exploited the strong capacity of colloidal gels solely made of oppositely charged gelatin nanospheres to obtain controlled release of angiogenic and osteogenic growth factors. The release kinetics of dual delivery of osteogenic bone morphogenetic protein-2 (BMP-2) and angiogenic basic fibroblast growth factor (bFGF) were investigated in vitro by radiolabeling the respective growth factors and monitoring their release in vitro. Furthermore, the effect of single or dual delivery of BMP-2 and bFGF on bone regeneration was evaluated in vivo using a rat femoral condyle defect model. The in vitro results confirmed that the delivery kinetics of BMP-2 and/or bFGF are more dependent on the degree of crosslinking than on the type of gelatin. Sequential release characterized by rapid release of angiogenic bFGF and more sustained release of BMP-2 was obtained by loading bFGF onto cationic nanospheres of low crosslinking density and BMP-2 onto anionic nanospheres of high crosslinking density. The in vivo study demonstrated the biocompatibility and biodegradability of bare colloidal gelatin gels, and did not show any adverse effects on the process of bone healing after 4week of implantation since the volumes of new bone formation were comparable to empty control defects. An obvious stimulatory effect on bone regeneration was observed for the colloidal gels loaded with BMP-2, whereas bFGF-loaded colloidal gelatin gels did not influence the rate of bone regeneration. In contrast, the combined delivery of BMP-2 and bFGF resulted into an inhibitory effect on osteogenesis under the current experimental conditions. Summarizing, the current study proved that nanostructured colloidal gelatin gels are suitable carriers for programmed and sustained release of multiple therapeutic proteins for tissue regeneration. [Copyright &y& Elsevier]

Calcium cross-linked alginate hydrogel has shown positive results for the treatment of myocardial infarction in both acute and chronic rat models. However, cross-linked alginate hydrogels possess poor mechanical properties, uncontrollable degradation, and poor cell adhesion and infiltration. In this study, covalent cross-linking of partially oxidized alginate and gelatin hydrogel was developed for myocardial infarction treatment, as compared to cross-linked alginate hydrogel and saline. Specifically, the gelation process, mechanical properties, and biodegradation of both cross-linked alginate hydrogel and oxidized alginate and gelatin hydrogel were examined in vitro and in vivo; and a rat myocardial infarction model was developed by injecting hydrogel into hearts, and postinjection, echocardiography was performed at 2, 4, and 6 weeks, respectively. Matrix metalloprotease-2/9 activity was also examined by in situ zymography on frozen slices of the treated hearts. Based on the results, that both hydrogels enhanced scar thickness and attenuated heart remodeling compared with the saline control group and that, compared to cross-linked alginate hydrogel, oxidized alginate and gelatin hydrogel exhibited the increased mechanical strength, enhanced angiogenesis, and stronger cell-recruiting capacity. It has also been illustrated that oxidized alginate and gelatin hydrogel–treated hearts have much weaker cardiac remodeling, enhanced extracellular matrix accumulation, and reduced matrix metalloprotease activity than cross-linked alginate hydrogel–treated ones. All results suggest oxidized alginate and gelatin hydrogel may be more suitable for the myocardial infarction treatment. [ABSTRACT FROM AUTHOR]

Abstract: Our objective in this study was to examine the effect of gelatin hydrogel (GH) sheets containing basic fibroblast growth factor (bFGF) on healing of proximal sesamoid bone transverse fractures in the horse. Ten healthy adult Thoroughbreds were used. The lateral proximal sesamoid bone of the left forelimb and the medial proximal sesamoid bone of the right forelimb were osteotomized, while the horses were under general anesthesia, and subsequently repaired by lag screw fixation using a single 4.5-mm cortical screw. A GH sheet containing 100 μg of bFGF was then sutured to the synovial membrane adjacent to the osteotomized proximal sesamoid bone. In the control group, the fracture was fixed with a lag screw, and the articular capsule was sutured. Fracture healing was assessed by radiographic examination once a week for 16 weeks after the operation. Radiographic examination of bone healing revealed significantly lower demineralization of the fracture line in the GH sheet-treated group than in the control group. The rate of demineralization of the fracture line in the GH sheet-treated group was significantly lower than that in the control group at 2, 4, and 8 weeks after the operation. In this study, we demonstrated that the use of a GH sheet containing bFGF promotes healing of proximal sesamoid bone fracture in the horse. Therefore, it is believed that this treatment strategy would be useful for quick recovery from bone fracture in the horse. [Copyright &y& Elsevier]

Abstract: Colloidal gels have recently emerged as a promising new class of materials for regenerative medicine by employing micro- and nanospheres as building blocks to assemble into integral scaffolds. To this end, physically crosslinked particulate networks are formed that are injectable yet cohesive. By varying the physicochemical properties of different particle populations, the suitability of colloidal gels for programmed delivery of multiple therapeutic proteins is superior over conventional monolithic gels that lack this strong capacity for controlled drug release. Colloidal gels made of biodegradable polymer micro- or nanospheres have been widely investigated over the past few years, but a direct comparison between micro- vs. nanostructured colloidal gels has not been made yet. Therefore, the current study has compared the viscoelastic properties and capacity for drug release of colloidal gels made of oppositely charged gelatin microspheres vs. nanospheres. Viscoelastic properties of the colloidal gelatin gels were characterized by rheology and simple injectability tests, and in vitro release of two selected osteogenic proteins (i.e. bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP)) from the colloidal gelatin gels was evaluated using radiolabeled BMP-2 and ALP. Nanostructured colloidal gelatin gels displayed superior viscoelastic properties over microsphere-based gels in terms of elasticity, injectability, structural integrity, and self-healing behavior upon severe network destruction. In contrast, microstructured colloidal gelatin gels exhibited poor gel strength and integrity, unfavorable injectability, and did not recover after shearing, resulting from the poor gel cohesion due to insufficiently strong interparticle forces. Regarding the capacity for drug delivery, sustained growth factor (BMP-2) release was obtained for both micro- and nanosphere-based gels, the kinetics of which were mainly depending on the particle size of gelatin spheres with the same crosslinking density. Therefore, the optimal gelatin carrier for drug delivery in terms of particle size and crosslinking density still needs to be established for specific clinical indications that require either short-term or long-term release. It can be concluded that nanostructured colloidal gelatin gels show great potential for sustained delivery of therapeutic proteins, whereas microstructured colloidal gelatin gels are not sufficiently cohesive as injectables for biomedical applications. [Copyright &y& Elsevier]

The article assesses shock reversal and required fluid volumes in septic shock patients. Results reveal that shock reversal was realized fast with synthetic colloids or crystalloids. Colloids use led to just marginally lower required volumes of resuscitation fluid. Findings also suggest that both low molecular weight hydroxyethyl starch and gelatin may impair renal function.

The release profiles and anti-bacterial properties of gentamycin (GEN) incorporated into in situ forming hydrogels for application as an in situ forming wound or burn dressing was investigated. Hydrogels were prepared by mixing gentamycin (GEN) with either a solution of the oxidized alginate in 0.1 M borax or a solution of gelatin in water and combining the two solutions. The release of GEN from these gels was studied by varying the order of mixing the drug with either oxidized alginate or gelatin. The antibacterial property of these gels was evaluated using gram negative P. aeruginosa and gram positive S. aureus. The gelation reaction between periodate-oxidized alginate and gelatin through Schiff's base formation was swift enabling in situ formation of GEN-loaded hydrogels. Drug release was slow when GEN was first mixed with oxidized alginate due to conjugation of the drug to the polymer through Schiff's base while release was more rapid when it was first mixed with gelatin. Drug payload also controlled the release of drug from the hydrogel matrix. Release occurred with an initial burst effect, followed by a relatively constant release. GEN released from the hydrogels was bactericidal against both strains of bacteria used for testing. [ABSTRACT FROM AUTHOR]

Abstract: The objective of this study is to evaluate the angiogenic effects induced by biodegradable gelatin hydrogel granules incorporating mixed platelet-rich plasma (PRP) growth factor mixture (PGFM) and bioactive basic fibroblast growth factor (bFGF). The PRP was prepared by a double-spinning technique for isolating animal bloods, followed by treatment with different concentrations of calcium chloride (CaCl2) solution. The CaCl2 solution treatment activated the platelets of PRP, allowing the release of various growth factors, such as platelet-derived growth factor (PDGF)-BB, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, and epithelial growth factor (EGF). In the PRP treated with different CaCl2 solutions, high amounts of representative platelet growth factor, PDGF-BB, VEGF, EGF, and TGF-β1 were detected in the CaCl2 concentrations of 1, 2, and 4wt.% compared with higher or lower ones. The PRP treated was impregnated into gelatin hydrogel granules freeze-dried at 37°C for 1h, and then the percentage of PGFM desorbed from the gelatin hydrogel granules was evaluated. The percentages of PDGF-BB, VEGF, EGF, and TGF-β1 desorbed tended to decrease with decreasing CaCl2 concentration. Taken together, the CaCl2 concentration to activate PRP for PGFM release was fixed at 2wt.%. In vitro release tests demonstrated that the PGFM was released from the gelatin hydrogel granules with time. For the gelatin hydrogels incorporating PGFM and bFGF, the time profile of PDGF-BB or bFGF release was in good correspondence with that of gelatin hydrogel degradation. The gelatin hydrogel granules incorporating mixed PGFM and bFGF were prepared and intramuscularly injected to a mouse leg ischemia model to evaluate the angiogenic effects in terms of histological and laser Doppler perfusion imaging examinations. As controls, hydrogel granules incorporating bFGF, PGFM, and platelet-poor plasma were used for the angiogenic evaluation. The number of blood vessels newly formed and the percentage of anti-α-smooth muscle actin antibody-positive cells increased around ischemic sites injected with the gelatin hydrogel granules incorporating mixed PGFM and bFGF, in marked contrast to other control groups. The blood reperfusion level of ischemic tissues was enhanced by the hydrogel granules incorporating mixed PGFM and bFGF, whereas no enhancement was observed for other groups. It is concluded that the dual-release system of PGFM and bFGF from gelatin hydrogel granules shows promise as a method to enhance angiogenic effects. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to develop and characterize a chitosan gel/gelatin microsphere (MSs) dual delivery system for sequential release of bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) to enhance osteoblast differentiation in vitro. We made and characterized the delivery system based on its degree of cross-linking, degradation, and release kinetics. We also evaluated the cytotoxicity of the delivery system and the effect of growth factors on cell response using pre-osteoblast W-20-17 mouse bone marrow stromal cells. IGF-1 was first loaded into MSs, and then the IGF-1-containing MSs were encapsulated into the chitosan gel which contained BMP-2. Cross-linking of gelatin with glyoxal via Schiff bases significantly increased thermal stability and decreased the solubility of the MSs, leading to a significant decrease in the initial release of IGF-1. Encapsulation of the MSs into the chitosan gel generated polyelectrolyte complexes by intermolecular interactions, which further affected the release kinetics of IGF-1. This combinational delivery system provided an initial release of BMP-2 followed by a slow and sustained release of IGF-1. Significantly greater alkaline phosphatase activity was found in W-20-17 cells treated with the sequential delivery system compared with other treatments (P <0.05) after a week of culture. [Copyright &y& Elsevier]

Abstract: There is a clear need for methods to provide a safe controlled release of therapeutic proteins, either to achieve and maintain high local protein concentrations, or for sustained systemic delivery. We have developed a protein delivery system that combines in situ cross-linkable polysaccharide hydrogels with gelatin. This formulation is injectable, easy to apply, and obviates the need for organic solvents or potentially toxic cross-linking agents in the formulation process. The cross-linked polysaccharides themselves (comprising hyaluronic acid, dextran and/or carboxymethylcellulose) provided prolonged release of fluorescently labeled albumin (FITC-albumin). The duration of release was markedly extended by the incorporation of gelatin into the formulation: FITC-albumin and interleukin-2 (IL-2) were released over the course of more than 3weeks. The IL-2 maintained >70% activity throughout that time. Gelatin also accelerated the gelation time of the hydrogels, and reduced their swelling in phosphate-buffered saline. The composite hydrogel (dextran–carboxymethylcellulose–gelatin) showed minimal cytotoxicity in vitro, and benign tissue reaction after subcutaneous injection in rats. [Copyright &y& Elsevier]

Purpose: Colloids are administered to more patients than crystalloids, although recent evidence suggests that colloids may possibly be harmful in some patients. The European Society of Intensive Care Medicine therefore assembled a task force to compile consensus recommendations based on the current best evidence for the safety and efficacy of the currently most frequently used colloids-hydroxyethyl starches (HES), gelatins and human albumin. Methods: Meta-analyses, systematic reviews and clinical studies of colloid use were evaluated for the treatment of volume depletion in mixed intensive care unit (ICU), cardiac surgery, head injury, sepsis and organ donor patients. Clinical endpoints included mortality, kidney function and bleeding. The relevance of concentration and dosage was also assessed. Publications from 1960 until May 2011 were included. The quality of available evidence and strength of recommendations were based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Recommendations and conclusions: We recommend not to use HES with molecular weight ≥200 kDa and/or degree of substitution >0.4 in patients with severe sepsis or risk of acute kidney injury and suggest not to use 6% HES 130/0.4 or gelatin in these populations. We recommend not to use colloids in patients with head injury and not to administer gelatins and HES in organ donors. We suggest not to use hyperoncotic solutions for fluid resuscitation. We conclude and recommend that any new colloid should be introduced into clinical practice only after its patient-important safety parameters are established. [ABSTRACT FROM AUTHOR]

In this study, two distinct systems of biomaterials were fabricated and their potential use as a bilayer scaffold (BS) for skin bioengineering applications was assessed. The initial biomaterial was a polycaprolactone/poly(lacto-co-glycolic acid) (PCL/PLGA) membrane fabricated using the electrospinning method. The PCL/PLGA membrane M-12 (12% PCL/10% PLGA, 80:20) displayed strong mechanical properties (stress/strain values of 3.01 ± 0.23 MPa/225.39 ± 7.63%) and good biocompatibility as demonstrated by adhesion of keratinocyte cells on the surface and ability to support cell proliferation. The second biomaterial was a hydrogel composed of 2% chitosan and 15% gelatin (50:50) crosslinked with 5% glutaraldehyde. The CG-3.5 hydrogel (with 3.5% glutaraldehyde (v/v)) displayed a high porosity, ≥97%, good compressive strength (2.23 ± 0.25 MPa), ability to swell more than 500% of its dry weight and was able to support fibroblast cell proliferation. A BS was fabricated by underlaying the membrane and hydrogel casting method to combine these two materials. The physical properties and biocompatibility were preliminarily investigated and the properties of the two biomaterials were shown to be complementary when combined. The upper layer membrane provided mechanical support in the scaffold and reduced the degradation rate of the hydrogel layer. Cell viability was similar to that in the hydrogel layer which suggests that addition of the membrane layer did not affect the biocompatibility. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) contains numerous growth factors that have angiogenic activities. However, the PRP-induced angiogenesis is limited by the short half-life period of growth factors. A new drug delivery system of biodegradable gelatin hydrogel was designed to achieve the controlled release of growth factors in PRP. The purpose of this study is to demonstrate the therapeutic efficacy of slow-release of PRP in the inducing of angiogenesis for critical ischemia. Methods: The PRP was prepared from the whole blood of inbred rats. Thirty-two rats underwent excision of the left femoral artery and its branches to create critical limb ischemia. The rats were randomized into four groups (n = 8 each): no treatment (control), intramuscular injection of platelet-poor plasma (PPP), PRP only, or a combination of PRP and gelatin hydrogel (PRP+Gel). Four weeks after the treatment, angiogenesis was evaluated by laser doppler, microangiogram, and immunohistology. Results: The resultant number of platelets for PRP was higher than that of PPP (p < 0.01). The concentrations of vascular endothelial growth factor, transforming growth factor-β1, and platelet-derived growth factor-BB were significantly higher in PRP animals than in PPP (p < 0.01). Although the PRP group improved tissue blood flow (82.7% ± 6.2%) compared with the control group or PPP group (69.6 ± 12.2 or 72.2 ± 11.8%, p < 0.05), the improvement of blood flow in the PRP+Gel group was significantly better (95.1% ± 8.0%, p < 0.05) than in the PRP group. Angiographic score in the PRP+Gel group was significantly higher than that in the control, PPP, and PRP groups (8.6 ± 2.1 versus 3.8 ± 0.8, 3.7 ± 0.6, and 5.6 ± 1.5, respectively; p < 0.01). Capillary density also increased immunohistologically in the PRP+Gel group when compared with the control, PPP, and PRP groups (p < 0.01). Conclusions: A controlled release system of PRP was effective in inducing angiogenesis for critical ischemia. The biodegradable gelatin hydrogel incorporating PRP as applicable could possibly be used to treat for patients with ischemic cardiomyopathy. [Copyright &y& Elsevier]

Abstract: To effectively repair or replace damaged tissues, it is necessary to design scaffolds with tunable structural and biomechanical properties that closely mimic the host tissue. In this paper, we describe a newly synthesized photocrosslinkable interpenetrating polymer network (IPN) hydrogel based on gelatin methacrylate (GelMA) and silk fibroin (SF) formed by sequential polymerization, which possesses tunable structural and biological properties. Experimental results revealed that IPNs, where both the GelMA and SF were independently crosslinked in interpenetrating networks, demonstrated a lower swelling ratio, higher compressive modulus and lower degradation rate as compared to the GelMA and semi-IPN hydrogels, where only GelMA was crosslinked. These differences were likely caused by a higher degree of overall crosslinking due to the presence of crystallized SF in the IPN hydrogels. NIH-3T3 fibroblasts readily attached to, spread and proliferated on the surface of IPN hydrogels, as demonstrated by F-actin staining and analysis of mitochondrial activity (MTT). In addition, photolithography combined with lyophilization techniques was used to fabricate three-dimensional micropatterned and porous microscaffolds from GelMA–SF IPN hydrogels, furthering their versatility for use in various microscale tissue engineering applications. Overall, this study introduces a class of photocrosslinkable, mechanically robust and tunable IPN hydrogels that could be useful for various tissue engineering and regenerative medicine applications. [Copyright &y& Elsevier]

A novel drug delivery system possessing prolonged release behavior is introduced to the field of carrier erythrocytes and nanotechnology-based drug delivery. Encapsulation of valproate-loaded nanogels inside human erythrocytes as a novel nanocell composite was the objective of the study to obtain a model novel drug delivery system with an intravenous sustained drug delivery characteristic. 'Ionotropic gelation' was used for the fabrication of hydrogel nanoparticles. The nanoparticles obtained were evaluated in vitro (particle size, transmitting electron microscopy, zeta potential, Fourier transform infrared spectroscopy, etc.). 'Hypotonic dialysis' was used to obtain nanoparticle-loaded erythrocytes. Finally, in vitro characterization tests were performed on nanoparticle-loaded erythrocytes. Number- and volume-based sizes, loaded amount (mg), loading ratio (%), and loading efficiency (%) of nanoparticles were, respectively, 61 ± 2 and 74 ± 2 nm, 20.6 ± 1.02 mg, 31.58 ± 1.86%, and 6.86 ± 0.41%. Spherical structure and slightly negative zeta potential of nanoparticles were confirmed. Erythrocytes were loaded by valproate-loaded nanoparticles (entrapment efficiency of 42.07 ± 3.6%). Carrier erythrocytes showed acceptable properties in vitro and demonstrated a prolonged drug release behavior over 3 weeks. This approach opens new horizons beyond the current applications of carrier erythrocytes for future investigations. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:1702-1711, 2011 [ABSTRACT FROM AUTHOR]

The objective of this study is to evaluate the potential of lactoferrin (LF), an iron-binding glycoprotein, to induce bone regeneration. A biodegradable gelatin hydrogel was prepared to allow LF release in vivo in a sustained fashion. When subcutaneously implanted into the back of mice, the gelatin hydrogel incorporating LF showed a longer LF retention period at the site of implantation than that of LF solution injection. An in vitro culture experiment with 3T3E1 cells (mouse-derived osteoblasts) revealed that the cells were proliferated to a significantly greater extent by the repeated addition of LF compared with a single addition of LF at the same dose. Following the implantation of gelatin hydrogels incorporating LF into a skull bone defect of rats, a significantly stronger bone regeneration at the defect was observed than in LF-free- or low-LF-treated rats. It is concluded that the sustained release from the gelatin hydrogels enables LF to enhance the in vivo activity of bone regeneration. [ABSTRACT FROM AUTHOR]

Abstract: Combining gelatins functionalized with the tyrosine-derived groups desaminotyrosine or desaminotyrosyl tyrosine with hydroxyapatite (HAp) led to the formation of composite materials with much lower swelling ratios than those of the pure matrices. Shifts of the infra-red (IR) bands related to the free carboxyl groups could be observed in the presence of HAp, which suggested a direct interaction of matrix and filler that formed additional physical cross-links in the material. In tensile tests and rheological measurements the composites equilibrated in water had increased Young’s moduli (from 200kPa up to 2MPa) and tensile strengths (from 57kPa up to 1.1MPa) compared with the matrix polymers without affecting the elongation at break. Furthermore, an increased thermal stability of the networks from 40 to 85°C could be demonstrated. The differences in the behaviour of the functionalized gelatins compared with pure gelatin as a matrix suggested an additional stabilizing bond between the incorporated aromatic groups and the HAp as supported by the IR results. The composites can potentially be applied as bone fillers. [Copyright &y& Elsevier]

In this study, poly(2-hydroxyethyl methacrylate) (pHEMA)-based superporous hydrogels were synthesized by radical polymerization of 2-hydroxyethyl methacrylate (HEMA) in the presence of a gas blowing agent, sodium bicarbonate. These hydrogels are: pHEMA, pHEMA-gelatin, glycerol phosphate (GP) cross-linked pHEMA-gelatin, glutaraldehyde (GA) cross-linked pHEMA-gelatin superporous hydrogels (SPHs) and pHEMA-hydroxyapatite (HA) superporous hydrogel composites (SPHCs). The hydrogels have a structure of interconnected pores with pore sizes of approx. 500 μm. Although the extent of swelling decreased when gelatin and HA were incorporated to the pHEMA structure, the time to reach the equilibrium swelling (approx. 20 s) was not affected so much. In the presence of gelatin and cross-linkers, mechanical properties significantly improved when compared with pHEMA SPH. Among all the synthesized hydrogels, pHEMA-HA SPHC showed great improvement in mechanical strength and its elastic modulus value was 0.027±0.002 N/mm2. Osteogenic activities of pHEMA-based scaffolds were examined by preosteoblastic MC3T3-E1 cell-culture studies. The mitochondrial activity test (MTT) showed that gelatin-containing scaffolds stimulated cell proliferation compared with other scaffolds, while alkaline phosphatase levels (ALP) and mineralization were found highest for the GP cross-linked pHEMA-gelatin SPH. However, pHEMA SPH and pHEMA-HA SPHC did not support cell proliferation and also differentiation. In conclusion, pHEMA-gelatin SPH and GP cross-linked pHEMA-gelatin SPH can be considered as potential scaffolds for bone tissue-engineering applications. [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate the use of thermosensitive hydrogels for intravesical cisplatin delivery into the bladder. Poly( N-isopropylacrylamide) (PNIPAM) was grafted onto hyaluronic acid (HA) to synthesize an HPN copolymer, which was further grafted with gelatin to form an HPNG copolymer. A 3% concentration of HPN and HPNG was sufficient to exert a thermosensitive response, whereas a concentration of 8% was needed for PNIPAM to form the hydrogel. The physicochemical and drug delivery properties were examined by scanning electron microscopy (SEM), the lower critical solution temperature (LCST), hydration ratio, and in vitro cisplatin release. The incorporation of HA and gelatin produced a different microstructure compared to the parent PNIPAM hydrogel. Gelatin conjugation increased the fibrous structure in the matrix. The LCSTs of PNIPAM, HPN, and HPNG were 32.3, 32.0, and 30.7°C, respectively. The copolymers showed an eightfold increase in the hydration capacity compared to PNIPAM, with no significant difference in values between HPN and HPNG. The release of cisplatin from an aqueous solution (control) was nearly complete after 8 h, compared to 85, 80, and 52% release from PNIPAM, HPN, and HPNG, respectively. In vivo evaluation of cisplatin levels in bladder tissues was performed following intravesical instillation in rats. When the dwell time was extended to 6 h, PNIPAM showed a sevenfold enhancement in the drug concentration in the bladder wall. HPNG also showed a twofold increase in the drug concentration. The administration of cisplatin by the HPN carrier did not change the drug accumulation compared to the control. Confocal laser scanning microscopic results confirmed the trend of drug absorption from various systems. A histological examination showed no adverse change in the urothelium with HPN or HPNG application. PNIPAM caused partial desquamation of umbrella cells. The thermosensitive hydrogels prepared in this study may be promising carriers for targeted drug delivery to the bladder. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:655-666, 2011 [ABSTRACT FROM AUTHOR]

Abstract: A diffusion-based model describing the drug release from a charged hydrogel (gelatin) microsphere undergoing enzymatic degradation is presented. The model elucidates the effect of glutaraldehyde, a crosslinking agent, on the release profile in terms of the initial drug distribution, diffusivity of the drug, degradation rate of gelatin and its ability to form polyionic complex with the drug. The model was validated by comparing with in vitro release of trypan blue, an acidic model drug, from basic gelatin microspheres. While drug release was not a simple function of glutaraldehyde concentration, the effective diffusivity was found to be inversely proportional to glutaraldehyde concentration in the form of a power function when the initial drug distribution was taken into consideration. For these reasons, the present model can accurately predict drug release with no adjustable parameters, given the collagenase concentration. The present model may help design certain release scenarios from biodegradable charged hydrogels for the oppositely charged drugs and biomolecules. [ABSTRACT FROM AUTHOR]

Abstract: pH-sensitive hydrogels based on methacrylic acid (MAA) and poly(ethylene glycol) macromonomer (PEGMEMA) entrapping diltiazem hydrochloride (DIL·HCl) were synthesized inside soft gelatin capsules for use as a new dosage form for oral drug administration. Different monomer compositions were used to evaluate their swelling and release behavior in two media: at low pH, simulating the acid pH of the stomach, and at pH 7, simulating the higher pH environment of the intestine. Both the swelling process and DIL·HCl release strongly depended on pH and monomer composition. Hydrogels with intermediate compositions showed diminished DIL·HCl release at pH 1.2. This fact was related to the formation of an impermeable outer skin, observed by magnetic resonance imaging (MRI). At pH 7 similar shaped release profiles were found for the four hydrogel compositions under investigation. At this neutral pH slow protonation of the carboxylate groups of MAA led to a swelling front and a dry core, also observed by MRI. As a consequence of this anomalous swelling, release curves exhibited a long period of zero order kinetics. This shows that the system could be a suitable candidate to develop a zero order release dosage form for oral administration of DIL·HCl. The swelling and dissolution processes were analyzed by different mathematical approaches. [ABSTRACT FROM AUTHOR]

Abstract: A series of hydrogels were fabricated from an aqueous solution of gelatin and carboxymethyl chitosan (CM-chitosan) by radiation-induced-crosslinking at ambient temperature. Several physicochemical and biological properties of the hydrogels were investigated to evaluate their potential as wound healing materials. By increasing the CM-chitosan content in the hybrid hydrogels, their swelling ability increased significantly, while the compressive modulus decreased. The miscibility between gelatin and CM-chitosan molecules led to a semi-interpenetrate network after crosslinking. Observed by SEM, scaffolds with a homogeneous interconnected pore structure were obtained after lyophilizing the hydrogels. The enzyme degradation rate of the hydrogels was controlled by adjusting the procedure, which could be matched to the healing rate of the wound. Furthermore, the gelatin/CM-chitosan hydrogels promoted cell attachment and rapid growth of fibroblasts on the material. Due to the high water absorption capacity, a similar compressive modulus with soft tissue, controllable biodegradation, and excellent biocompatibility, the gelatin/CM-chitosan hybrid hydrogels have potential as skin scaffolds and wound healing materials. [Copyright &y& Elsevier]

Abstract: In this paper, a novel class of microspheric hydrogels was synthesized by grafting of N-isopropyacrylamide (NIPAAm) with gelatin. The possibility of inserting commercial gelatin in a crosslinked structure bearing thermo-sensitive moieties, by radical process, represents an interesting innovation that significantly improves the device performance, opening new applications in biomedical and pharmaceutical fields. This synthetic approach allows a modification of the polymeric network composition, producing hydrogels with suitable physico-chemical properties and a transition temperature higher than NIPAAm homopolymers. The incorporation of monomers into the network was confirmed by infrared spectroscopy, and the composition of the polymerization feed was found to strictly influence the network density and the shape of hydrogels. Thermal analyses showed negative thermo-responsive behaviour with shrinking/swelling transition values in the temperature range 34.6–34.8°C, according to the amount of the hydrophilic portions in the network. In order to test the preformed materials as drug carriers, diclofenac sodium salt was loaded into the spherical microparticles. After the determination of the drug entrapment percent, drug release profiles in media at different temperature were analysed. By using semi-empirical equations, the release mechanism was extensively studied and the diffusional contribution was evaluated. [ABSTRACT FROM AUTHOR]

Abstract: The cellular microenvironment plays an integral role in improving the function of microengineered tissues. Control of the microarchitecture in engineered tissues can be achieved through photopatterning of cell-laden hydrogels. However, despite high pattern fidelity of photopolymerizable hydrogels, many such materials are not cell-responsive and have limited biodegradability. Here, we demonstrate gelatin methacrylate (GelMA) as an inexpensive, cell-responsive hydrogel platform for creating cell-laden microtissues and microfluidic devices. Cells readily bound to, proliferated, elongated, and migrated both when seeded on micropatterned GelMA substrates as well as when encapsulated in microfabricated GelMA hydrogels. The hydration and mechanical properties of GelMA were demonstrated to be tunable for various applications through modification of the methacrylation degree and gel concentration. The pattern fidelity and resolution of GelMA were high and it could be patterned to create perfusable microfluidic channels. Furthermore, GelMA micropatterns could be used to create cellular micropatterns for in vitro cell studies or 3D microtissue fabrication. These data suggest that GelMA hydrogels could be useful for creating complex, cell-responsive microtissues, such as endothelialized microvasculature, or for other applications that require cell-responsive microengineered hydrogels. [Copyright &y& Elsevier]

Background: Colloids are often used after cardiac surgery as intravascular volume replacement therapy. Cardiac surgical patients have an increased risk of bleeding. Both hydroxyethylstarch (HES) and gelatin solutions impair haemostasis. We examined the impact and dose effect on coagulation of HES 130/0.4, gelatin, or Ringer's acetate solutions after cardiac surgery. [ABSTRACT FROM PUBLISHER]

Abstract Purpose  To elucidate the key parameters affecting solute transport from semi-interpenetrating networks (sIPNs) comprised of poly(ethylene glycol) diacrylate (PEGdA) and gelatin that are partially crosslinked, water-swellable and biodegradable. Effects of material compositions, solute size, solubility, and loading density have been investigated. Materials and Methods  sIPNs of following gelatin/PEGdA weight-to-weight ratios were prepared: 10:15, 10:20, 10:30, 15:15, 20:15. Five model solutes of different physicochemical properties were selected, i.e. silver sulfadiazine (AgSD), bupivacaine hydrochloride (Bup), sulfadiazine sodium (NaSD), keratinocyte growth factor (KGF), and bovine serum albumin conjugated with fluorescein isothiocyanate (BSA-FITC). Release studies were performed and the results were analyzed using three hydrogel based common theories (free volume, hydrodynamic and obstruction). Results  The release kinetics of model solutes was influenced by each factor under investigation. Specifically, the initial release rates and intra-gel diffusivity decreased with increasing PEGdA content or increasing solute molecular weight. However, the initial release rate and intra-gel diffusivity increased with increasing gelatin content or increasing solute water solubility, which contradicted with the classical hydrogel based solute transport theories, i.e. increasing polymer volume leads to decreased solute diffusivity within the gel. Conclusion  This analysis provides structure-functional information of the sIPN as a potential therapeutic delivery matrix. [ABSTRACT FROM AUTHOR]

Objectives: We hypothesized that erythropoietin (EPO)-immersed gelatin hydrogel microspheres (GHM) injected into ischemic legs might continuously release a small amount of EPO to locally stimulate angiogenesis without unfavorable systemic effects. Background: EPO is a potent angiogenic factor, but its use for relieving ischemic organs is limited because of the untoward systemic erythrogenic effect and its short half-life in plasma. Methods: The right femoral arteries of BALB/c mice were ligated. Recombinant human EPO (5,000 IU/kg)-immersed GHM was injected into the right hind limb muscles (n = 12); the control groups included a saline-injected group (n = 12), an EPO-injected group (n = 8), and an empty GHM-injected group (n = 8). Results: Eight weeks later, improvement of blood perfusion to the ischemic limb was significantly augmented in the EPO-GHM group compared with any of the control groups. There was no increase in the hemoglobin level, nor was there any increase in endothelial progenitor cells. However, capillary and arteriolar densities were significantly increased in this group. Although the treatment did not affect the levels of vascular endothelial growth factor or interleukin-1 beta, it up-regulated the EPO receptor and matrix metalloproteinase-2 and activated the downstream signaling of Akt and also endothelial nitric oxide synthase in ischemic limbs, which might have been associated with the evident angiogenic and arteriogenic effects in the present system. Conclusions: The present drug delivery system is suggested to have potential as a novel noninvasive therapy for ischemic peripheral artery disease. [Copyright &y& Elsevier]

Current guidelines on initial haemodynamic stabilization in shock states suggest infusion of either natural or artificial colloids or crystalloids. However, as the volume of distribution is much larger for crystalloids than for colloids, resuscitation with crystalloids alone requires more fluid and results in more oedema, and may thus be inferior to combination therapy with colloids. This chapter describes the currently available synthetic colloid solutions [i.e., dextran, gelatin and hydroxyethyl starch (HES)] in detail, and critically discusses their specific effects including potential adverse effects. Literature was selected from medical databases (including Medline and the Cochrane library), as well as references extracted from the available publications. Dextrans appear to have the most unfavourable risk/benefit ratio among the currently available synthetic colloids due to their relevant anaphylactoid potential, risk of renal failure and, particularly, their major impact on haemostasis. The effects of gelatin on kidney function are currently unclear, but potential disadvantages of gelatin include a high anaphylactoid potential and a limited volume effect compared with dextrans and HESs. Modern HES preparations have the lowest risk of anaphylactic reactions among the synthetic colloids. Older HES preparations (hetastarch, hexastarch and pentastarch) have repeatedly been reported to impair renal function and hemostasis, especially when the dose limit provided by the manufacturer is exceeded, but no such effects have been reported to date for modern tetrastarches compared with gelatin and albumin. However, no large-scale clinical studies have investigated the impact of tetrastarches on the incidence of renal failure in critically ill patients. When considering the efficacy and risk/benefit profile of synthetic colloids, modern tetrastarches appear to be most suitable for intensive care medicine, given their high volume effect, low anaphylactic potential and predictable pharmacokinetics. However, the impact of tetrastarch solutions on mortality and renal function in septic patients has not been fully determined, and further comparison with crystalloids in prospective, randomized studies is required. Such studies are currently ongoing and their results should be awaited before drawing final conclusions on the HES preparations. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes the preparation of oxidized hyaluronan crosslinked gelatin microspheres for drug delivery. Microspheres were prepared by a modified water-in-oil-emulsion crosslinking method, where three-dimensional crosslinked hydrogel microspheres formed in the absence of any extraneous crosslinker. SEM analyses of the microspheres showed rough surfaces in their dried state with an average diameter of 90μm. Lyophilization of fully swollen microspheres revealed a highly porous structure. Guanidinoethyl disulfide (GED) was used as a model drug for incorporation into the microspheres; encapsulation of GED was confirmed by HPLC. There was an inverse correlation between the diameters of the microspheres with their GED loading. Macrophage was used as a model cell to evaluate the in vitro efficacy of GED release from the microspheres. The in vivo efficacy of the microspheres was further validated in a mouse full-thickness transcutaneous dermal wound model through suppression of cell infiltration. [Copyright &y& Elsevier]

Background: Synthetic colloid administration is a common practice for preventing perioperative hypovolemia and consecutive circulatory failure in children. This prospective, randomized study was conducted to investigate the effects of two different unbalanced synthetic colloid solutions on acid–base equilibrium in children. Methods: Fifty pediatric patients (aged 0–12 years) scheduled for major pediatric surgery were randomized to receive either 10 ml·kg−1 of 6% hydroxyethyl starch solution 130/0.42 (HES) or 4% modified fluid gelatin (GEL) to maintain adequate systemic hemodynamics. Before and after colloid administration, a blood sample was collected to analyze hemoglobin, hematocrit, electrolytes, and acid–base parameters. The anion gap and the strong ion difference (SID) were calculated using standard formulas. Results: Both HES and GEL administration caused a significant increase in plasma chloride concentration ( P < 0.01) and an accompanying decrease in SID ( P < 0.01). In the HES group, the anion gap decreased significantly ( P < 0.01) whereas the anion gap remained stable in the GEL group. In both groups, initial actual base excess and pH did not change significantly after colloid administration. Conclusions: Moderate intraoperative plasma replacement with unbalanced synthetic colloids HES and GEL leads to a decrease in SID and, in the case of HES, to a significant decrease in the anion gap in children. These alterations may result in a possible misinterpretation when the anion gap and SID are used for differential diagnosis of metabolic disturbances during major pediatric surgery. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we investigated the in vitro and in vivo biological activities of bone morphogenetic protein 2 (BMP-2) released from four sustained delivery vehicles for bone regeneration. BMP-2 was incorporated into (1) a gelatin hydrogel, (2) poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in a gelatin hydrogel, (3) microspheres embedded in a poly(propylene fumarate) (PPF) scaffold and (4) microspheres embedded in a PPF scaffold surrounded by a gelatin hydrogel. A fraction of the incorporated BMP-2 was radiolabeled with 125I to determine its in vitro and in vivo release profiles. The release and bioactivity of BMP-2 were tested weekly over a period of 12 weeks in preosteoblast W20-17 cell line culture and in a rat subcutaneous implantation model. Outcome parameters for in vitro and in vivo bioactivities of the released BMP-2 were alkaline phosphatase (AP) induction and bone formation, respectively. The four implant types showed different in vitro release profiles over the 12-week period, which changed significantly upon implantation. The AP induction by BMP-2 released from gelatin implants showed a loss in bioactivity after 6 weeks in culture, while the BMP-2 released from the other implants continued to show bioactivity over the full 12-week period. Micro-CT and histological analysis of the delivery vehicles after 6 weeks of implantation showed significantly more bone in the microsphere/PPF scaffold composites (Implant 3, p <0.02). After 12 weeks, the amount of newly formed bone in the microsphere/PPF scaffolds remained significantly higher than that in the gelatin and microsphere/gelatin hydrogels (p <0.001), however, there was no statistical difference compared to the microsphere/PPF/gelatin composite. Overall, the results from this study show that BMP-2 could be incorporated into various bone tissue engineering composites for sustained release over a prolonged period of time with retention of bioactivity. [Copyright &y& Elsevier]

We report a novel 3-D cavity wound dressing based on a hydrogel–elastomer Interpenetrating Polymer Network (IPN) fabricated into an open-mesh architecture. IPN fibers used to form the dressing were produced by a wet spinning method and optimized in two steps. A factorial experiment was first conducted to identify key parameters that controlled fiber properties. We observed that gelatin wt% played a major role in determining fiber yield, swelling, strength and stability. Other contributing factors included coagulation solution composition, gelatin type, and pre- and post-UV irradiation time. The key factors were then further evaluated individually to achieve a condition that provided a combination of good swelling, mechanical properties and stability. The concentration of the gelatin/HydroThaneTM extrusion solution significantly affected fiber formation and properties, presumably due to the changes in solution viscosity. The effects of pre-UV irradiation were also ascribed to its impact on the solution viscosity and became negligible at higher concentrations when viscosity is mainly controlled by concentration. The composition of the coagulation bath influenced the fiber swelling and wet stress. These results, taken together with our previous studies, suggest that our biomaterial would provide a combination of mechanical and swelling properties suitable for wound dressing applications. [ABSTRACT FROM AUTHOR]

Hypothesis Safety differences exist among colloids widely used for fluid management in acutely ill patients, as judged according to the comparative incidence of adverse events. Data Sources Colloid safety data for human subjects were sought, without language or time period restrictions, by means of computer searches of bibliographic and clinical trial databases, hand searches of medical journals and Index Medicus, inquiries with investigators and colloid suppliers, and examination of reference lists. Search terms included "colloids", "morbidity", and "mortality". Study Selection Controlled trials, cohort studies, pharmacovigilance studies, and prior meta-analyses were independently selected by 2 unblinded investigators. Of 189 candidate studies, 113 were included, with safety data encompassing 1.54 × 106 patients and 1.09 × 108 colloid infusions. Data Extraction Two unblinded investigators independently extracted data. Study limitations and confounding factors were tabulated. Data Synthesis With albumin as the reference colloid, the incidence rate ratio for anaphylactoid reactions was 4.51 (95% confidence interval, 2.06-9.89) after hydroxyethyl starch administration, 2.32 (95% confidence interval, 1.21-4.45) after dextran, and 12.4 (95% confidence interval, 6.40-24.0) after gelatin. Pruritus occurrence was significantly increased by hydroxyethyl starch exposure (odds ratio, 1.78; 95% confidence interval, 1.23-2.58). Artificial colloid administration was consistently associated with coagulopathy and clinical bleeding, most frequently in cardiac surgery patients receiving hydroxyethyl starch. On the basis of large-scale pharmacovigilance study results, albumin infusion resulted in a low rate of both total adverse events (3.1 to 8.6 per 105 infusions) and serious adverse events (1.29 per 106 infusions). Conclusions Significant safety differences exist among colloids. Therefore, conclusions regarding the clinical usefulness of colloids as a fluid class should be formed with caution. [ABSTRACT FROM AUTHOR]

Introduction Self-made devices composed of agar and gelatin gel were used for resident training in intra-axial brain tumor resection. The mixture gel of agar and gelatin is retractable and can be suctioned. Hardness of the gel depends on the concentration of the solution. Therefore, by changing the concentration, it is easy to make gels of various hardness. Methods In this study, a mass of gel that looked like a tumor was placed into another gel that looked like the brain. A part of the “brain” was regarded as the eloquent area. Three types of “tumor” were prepared: hard, moderately hard, and soft tumors. Residents tried to remove the tumor entirely with minimal brain invasion. The training was repeated with 3 types of gel. After resection, the weight of the residual tumor, resected normal brain, and resected eloquent area were measured, and the time taken for removal was recorded. Results These data were compared between residents and neurosurgeons. We also analyzed how these data improved with repeated practice. In most cases, residual tumor, resected normal brain, resected eloquent area, and time taken for removal were less in neurosurgeons than in residents. Repeated training made residents more skillful. The responses of the trainees were almost all favorable. Conclusions Our devices with “tumors” of various hardness appear to be suitable for resident training in each surgical skill. For the next step of this study, we will attempt to fabricate more practical 3-dimensional gel models for presurgical simulation. [ABSTRACT FROM AUTHOR]

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