Cellulose fibres enhance the function of hemostatic composite medical sealants.

Tissue adhesives and sealants offer promising alternatives to traditional wound closure methods, but the existing trade-off between biocompatibility and strength is still a challenge. The current study explores the potential of a gelatin-alginate-based hydrogel, cross-linked with a carbodiimide, and loaded with two functional fillers, the hemostatic agent kaolin and cellulose fibres, to improve the hydrogel's mechanical strength and hemostatic properties for use as a sealant. The effect of the formulation parameters on the mechanical and physical properties was studied, as well as the biocompatibility and microstructure. The incorporation of the two functional fillers resulted in a dual micro-composite structure, with uniform dispersion of both fillers within the hydrogel, and excellent adhesion between the fillers and the hydrogel matrix. This enabled to strongly increase the sealing ability and the tensile strength and modulus of the hydrogel. The fibres' contribution to the enhanced mechanical properties is more dominant than that of kaolin. A combined synergistic effect of both fillers resulted in enhanced sealing ability (247%), tensile strength (400%), and Young's modulus (437%), compared to the unloaded hydrogel formulation. While the incorporation of kaolin almost did not affect the physical properties of the hydrogel, the incorporation of the fibres strongly increased the viscosity and decreased the gelation time and swelling degree. The cytotoxicity tests indicated that all studied formulations exhibited high cell viability. Hence, the studied new dual micro-composite hydrogels may be suitable for medical sealing applications, especially when it is needed to get a high sealing effect within a short time. The desired hemostatic effect is obtained due to kaolin incorporation without affecting the physical properties of the sealant. Understanding the effects of the formulation parameters on the hydrogel's properties enables the fitting of optimal formulations for various medical sealing applications.

Closure of Long Surgical Incisions with Hemostatic Tissue Adhesive in a Porcine Skin Model.

OBJECTIVE: Skin adhesives offer many advantages over traditional wound-closure devices. Recently, the current research group reported on tissue adhesives composed of natural polymers (gelatin and alginate), which are biocompatible with mechanical properties suitable for tissue adhesion. The objective of the present study was to conduct clinical and histologic assessment of this hemostatic bioadhesive in the healing of long skin incisions (≥4 cm) in comparison with traditional and commercially available methods. METHODS: Researchers created 24 long incisions on the ventral side of two domestic pigs to compare four different treatment modalities: two topical bioadhesives based on gelatin and alginate combined with the hemostatic agent kaolin, nylon sutures, and commercial tissue adhesive N-butyl-2-cyanoacrylate. The bioadhesive compounds were spread on the incision surface and then mixed either manually or with a double-headed syringe. After 14 days, clinical and histologic measurements were performed to evaluate the healing phase of the wounds. RESULTS: The bioadhesive formulation that contained a relatively low crosslinker concentration demonstrated superior results to the formulation that contained a standard crosslinker concentration. However, no significant statistical differences were observed compared with the control incisions (sutures and commercial adhesive N-butyl-2-cyanoacrylate). This was verified by immunohistochemical analysis for epithelial integrity and scar formation as well as by clinical assessment. CONCLUSIONS: This newly developed bioadhesive demonstrated suitable properties for the closure of long incisions in a porcine skin model.

Injectable metronidazole-eluting gelatin-alginate hydrogels for local treatment of periodontitis.

Infection of the periodontal pocket presents two major challenges for drug delivery: administration into the periodontal pocket and a high fluid clearance rate in the pocket. The current study aimed to develop and study a novel hydrogel system for delivery of the antibiotic drug metronidazole directly into the periodontal pocket via injection followed by in situ gelation. The natural polymers gelatin and alginate served as basic materials, and their crosslinking using a carbodiimide resulted in a dual hydrogel network. The study focused on the effects of the hydrogel's formulation parameters on the drug release profile and the hydrogel's physical and mechanical properties. A cell viability test was conducted on human fibroblasts. The metronidazole-loaded hydrogels demonstrated a decreasing release rate with time, where most of the drug eluted within 24 h. These hydrogels exhibited fibroblast viability of at least 75% after 24 and 48 h, indicating that they are highly biocompatible. Although the alginate concentration used in this study was relatively low, it had a strong effect on the physical as well as the mechanical properties of the hydrogel. An increase in the alginate concentration increased the crosslinking rate and enabled enhanced entanglement of the 3D structure, resulting in a decrease in the gelation time (less than 10 s) and swelling degree, which are both desired for the studied periodontal application. Increasing the gelatin concentration without changing the crosslinker concentration resulted in significant changes in the physical properties and slight changes in the mechanical properties. Metronidazole incorporation slightly decreased the hydrophilicity of the hydrogel and therefore also its viscosity, and affected the sealing ability and the tensile and compression moduli. The developed hydrogels exhibited controllable mechanical and physical properties, can target a wide range of conditions, and are therefore of high significance in the field of periodontal treatment.

Self-Healing, Self-Adhesive and Stable Organohydrogel-Based Stretchable Oxygen Sensor with High Performance at Room Temperature.

With the advent of the 5G era and the rise of the Internet of Things, various sensors have received unprecedented attention, especially wearable and stretchable sensors in the healthcare field. Here, a stretchable, self-healable, self-adhesive, and room-temperature oxygen sensor with excellent repeatability, a full concentration detection range (0-100%), low theoretical limit of detection (5.7 ppm), high sensitivity (0.2%/ppm), good linearity, excellent temperature, and humidity tolerances is fabricated by using polyacrylamide-chitosan (PAM-CS) double network (DN) organohydrogel as a novel transducing material. The PAM-CS DN organohydrogel is transformed from the PAM-CS composite hydrogel using a facile soaking and solvent replacement strategy. Compared with the pristine hydrogel, the DN organohydrogel displays greatly enhanced mechanical strength, moisture retention, freezing resistance, and sensitivity to oxygen. Notably, applying the tensile strain improves both the sensitivity and response speed of the organohydrogel-based oxygen sensor. Furthermore, the response to the same concentration of oxygen before and after self-healing is basically the same. Importantly, we propose an electrochemical reaction mechanism to explain the positive current shift of the oxygen sensor and corroborate this sensing mechanism through rationally designed experiments. The organohydrogel oxygen sensor is used to monitor human respiration in real-time, verifying the feasibility of its practical application. This work provides ideas for fabricating more stretchable, self-healable, self-adhesive, and high-performance gas sensors using ion-conducting organohydrogels.

Cell viability of novel composite hydrogels loaded with hydroxyapatite for oral and maxillofacial bone regeneration.

The development of hydrogels for maxillofacial bone regeneration holds vast potential. However, some challenges need to be addressed to further their application in clinical settings. One challenge is optimizing cell viability. To improve mechanical strength, various materials have been investigated; however, incorporation of these materials within the hydrogel network may affect cell viability. The purpose of this study was to evaluate the cell viability of novel gelatin-alginate composite hydrogels loaded with hydroxyapatite (HA) and nano-hydroxyapatite (n-HA) for maxillofacial bone regeneration. Nine different hydrogels were prepared: three loaded with 0.5%, 1%, and 3% w/v HA; three loaded with 0.25%, 0.5%, and 1% w/v n-HA; one not loaded as a control and two HA and n-HA hydrogels with a lower concentration of the EDC crosslinker. Cell viability of human osteoblasts exposed to the hydrogels as affected by the HA type, size, and concentration, as well as to the crosslinker concentration, was investigated. An Alamar Blue assay was used to evaluate cell viability in the presence of hydrogel extracts and in aqueous solutions (without the hydrogel). A qualitative model was developed for explaining cell viability and growth. Higher percentages of cell viability were observed in the hydrogels loaded with hydroxyapatite as compared with the control. The effect of HA-related parameters, i.e., particle size and concentration, was found to increase the cytotoxic effect, as expressed in lower cell viability. The most favorable composites were the n-HA hydrogels. The incorporation of n-HA in the hydrogel to form a composite seems to be a very promising approach for maxillofacial bone regeneration applications.

In vivo study of the efficacy of bupivacaine-eluting novel soy protein wound dressings in a rat burn model.

Dealing with wound related pain is an integral part of treatment. Systemic administration of analgesic and anesthetic agents is a common solution for providing pain relief to patients but comes at a risk of severe side effects as well as addiction. To overcome these issues, research efforts were madeto provide a platform for local controlled release of pain killers. We have developed a bilayer soy protein-based wound dressing for the controlled local release of bupivacaine to the wound site. The combination of a dense and a porous layer provides a platform for cell growth and proliferation as well as physical protection to the wound site. The current study focuses on the in vitro bupivacaine release profile from the dressing and the corresponding in vivo results of pain levels in a second-degree burn model on rats. The Rat Grimace Scale method and the Von Frey filaments method were used to quantify both, spontaneous pain and mechanically induced pain. A high burst release of 61.8 ± 1.9% of the loaded drug was obtained during the initial hour, followed by a slower release rate during the following day. The animal trials show that the RGS scores of the bupivacaine-treated group were significantly lower than these of the untreated group, proving a decrease of 51-68% in pain levels during days 1-3 after burn. Hence, successful pain reduction of spontaneous pain as well as mechanically induced pain, for at least three days after burn was achieved. It is concluded that our novel bupivacaine eluting soy protein wound dressings are a promising new concept in the field of local controlled drug release for pain management.

FITC-Dextran Release from Cell-Embedded Fibrin Hydrogels.

Fibrin hydrogel is a central biological material in tissue engineering and drug delivery applications. As such, fibrin is typically combined with cells and biomolecules targeted to the regenerated tissue. Previous studies have analyzed the release of different molecules from fibrin hydrogels; however, the effect of embedded cells on the release profile has yet to be quantitatively explored. This study focused on the release of Fluorescein isothiocyanate (FITC)-dextran (FD) 250 kDa from fibrin hydrogels, populated with different concentrations of fibroblast or endothelial cells, during a 48-h observation period. The addition of cells to fibrin gels decreased the overall release by a small percentage (by 7-15% for fibroblasts and 6-8% for endothelial cells) relative to acellular gels. The release profile was shown to be modulated by various cellular activities, including gel degradation and physical obstruction to diffusion. Cell-generated forces and matrix deformation (i.e., densification and fiber alignment) were not found to significantly influence the release profiles. This knowledge is expected to improve fibrin integration in tissue engineering and drug delivery applications by enabling predictions and ways to modulate the release profiles of various biomolecules.

Bupivacaine-eluting soy protein structures for controlled release and localized pain relief: An in vitro and in vivo study.

Burn pain is known to be excruciating, and while burn care has greatly advanced, treatment for burn-related pain is lacking. Current pain relief methods include systemic administration of analgesics, which does not provide high drug concentration at the wound site. In the present study, soy protein was used as the base material for bupivacaine-loaded hybrid wound dressings. The effect of the formulation on the drug release profile was studied using high performance liquid chromatography, and the cytotoxicity was tested on human fibroblasts. A second-degree burn model in rats was used to quantify the efficacy of the wound dressings in vivo, using the Rat Grimace Scale. All tested films exhibited high biocompatibility, and the drug release profiles showed rapid release during the initial 5 hr and a continuous slower release for another 24 hr. Significant pain relief was achieved in the animal trials, proving a decrease of 51-68% in pain levels during days 1-3 post-burn. Hence, the results indicate a safe and controlled bupivacaine release for a period of more than 24 hr, effectively treating pain caused by second-degree burns. The understanding of the formulation-properties effects, together with our in vivo study, enables to advance this field toward tailorable systems with high therapeutic potential.

In vitro characterization of novel multidrug-eluting soy protein wound dressings.

Polymers derived from natural sources are of interest in the scientific and medical communities, especially soy protein which exhibits low immunogenicity and good mechanical properties, and supports cell proliferation. Soy protein is cost-effective compared to other natural polymers and is attractive also due to its non-animal origin and relatively long storage stability. In the current study, hybrid film structures were developed and studied as a novel wound dressing platform with controlled release of three bioactive agents. The dense top layer is designed to provide mechanical support, control the water vapor permeability and to elute the antibiotic drug cloxacillin and the analgesic drug bupivacaine to the wound site. The porous sub-layer is designed to absorb the wound exudates and release the hemostatic agent tranexamic acid for bleeding control. The results show that the formulation parameters, i.e. crosslinker and plasticizer concentrations, affected the mechanical properties of the wound dressings as well as relevant physical properties (water vapor transmission rate and swelling kinetics), but had almost no effect on the drug-release profiles. While the antibiotic drug and the analgesic drug were released within several hours, the hemostatic agent was released within several minutes, according to the well designed hybrid structure. In conclusion, our novel soy protein hybrid wound dressings are biocompatible, can deliver various drugs simultaneously in a controlled fashion for each drug individually, and can be adjusted to suit various types of wounds by altering their properties through formulation effects.

Catheter Injectable Hydrogel-Based Scaffolds for Tissue Engineering Applications in lung disease.

BACKGROUND: Chronic lung diseases, especially emphysema and pulmonary fibrosis, are the third leading cause of mortality worldwide. Their treatment includes symptom alleviation, slowing of the disease progression, and ultimately organ transplant. Regenerative medicine represents an attractive alternative. OBJECTIVES: To develop a dual approach to lung therapy by engineering a platform dedicated to both remodeling pulmonary architecture (bronchoscopic lung volume reduction) and regeneration of lost respiratory tissue (scaffold). METHODS: The authors developed a hydrogel scaffold based on the natural polymers gelatin and alginate. The unique physical properties allow its injection through long catheters that pass through the working channel of a bronchoscope. The scaffold might reach the diseased area; thus, serving a dual purpose: remodeling the lung architecture as a lung volume reduction material and developing a platform for tissue regeneration to allow for cell or organoid implant. RESULTS: The authors' novel hydrogel scaffold can be injected through long catheters, exhibiting the physical and mechanical properties necessary for the dual treatment objectives. Its biocompatibility was analyzed on human fibroblasts and mouse mesenchymal cells. Cells injected with the scaffold through long narrow catheters exhibited at least 70% viability up to 7 days. CONCLUSIONS: The catheter-injectable gelatin-alginate hydrogel represents a new concept, which combines tissue engineering with minimal invasive procedure. It is an inexpensive and convenient to use alternative to other types of suggested scaffolds for lung tissue engineering. This novel concept may be used for additional clinical applications in regenerative medicine.

Structuring of composite hydrogel bioadhesives and its effect on properties and bonding mechanism.

Bioadhesives are polymeric hydrogels that can adhere to a tissue after crosslinking and are an essential element in nearly all surgeries worldwide. Several bioadhesives are commercially available. However, none of them are ideal. The main limitation of current tissue adhesives is the tradeoff between biocompatibility and mechanical strength, especially in wet hemorrhagic environments. Our novel bioadhesives are based on the natural polymers gelatin (coldwater fish) and alginate, crosslinked by carbodiimide (EDC). Two types of hemostatic agents with a layered silicate structure, montmorillonite (MMT) and kaolin, were loaded in order to improve the sealing ability in a hemorrhagic environment. The effect of the adhesive's components on its mechanical strength was studied by three different methods - burst strength, lap shear and compression. The viscosity, gelation time and structural features of the adhesive were also studied. A qualitative model that describes the effect of the bioadhesive's parameters on the cohesive and adhesive strength was developed. A formulation based on 400mg/mL gelatin, 10mg/mL alginate and 20mg/mL EDC was found as optimal, enabling a burst strength of 387mmHg. Incorporation of kaolin increased the burst strength by 25% due to microcomposite structuring, whereas MMT increased the burst strength by 50% although loaded in a smaller concentration, due to nano-structuring effects. This research clearly shows that the incorporation of kaolin and MMT in gelatin-alginate surgical sealants is a very promising novel approach for improving the bonding strength and physical properties of surgical sealants for use in hemorrhagic environments. STATEMENT OF SIGNIFICANCE: The current manuscript focuses on novel bioadhesives, based on natural polymers and loaded with hemostatic agents with a layered silicate structure, in order to improve the sealing ability in hemorrhagic environment. Such composite bioadhesives have not been developed and studied before. The effect of the adhesive's components on its mechanical strength was studied by three different methods, as well as the physical properties and structural features. Thorough understanding of these unique biomaterials resulted in a qualitative model which describes the effect of the bioadhesive's parameters on the cohesive and adhesive strength. Thus, structure-property-function relationships are presented. Structuring of the composite bioadhesives and its effect of the properties and bonding mechanism, are expected to be of high interest to Acta readership.

Microstructure and in vitro cellular response to novel soy protein-based porous structures for tissue regeneration applications.

Interest in the development of new bioresorbable structures for various tissue engineering applications is on the rise. In the current study, we developed and studied novel soy protein-based porous blends as potential new scaffolds for such applications. Soy protein has several advantages over the various types of natural proteins employed for biomedical applications due to its low price, non-animal origin and relatively long storage time and stability. In the present study, blends of soy protein with other polymers (gelatin, pectin and alginate) were added and chemically cross-linked using the cross-linking agents carbodiimide or glyoxal, and the porous structure was obtained through lyophilization. The resulting blend porous structures were characterized using environmental scanning microscopy, and the cytotoxicity of these scaffolds was examined in vitro. The biocompatibility of the scaffolds was also evaluated in vitro by seeding and culturing human fibroblasts on these scaffolds. Cell growth morphology and adhesion were examined histologically. The results show that these blends can be assembled into porous three-dimensional structures by combining chemical cross-linking with freeze-drying. The achieved blend structures combine suitable porosity with a large pore size (100-300 µm). The pore structure in the soy-alginate scaffolds possesses adequate interconnectivity compared to that of the soy-gelatin scaffolds. However, porous structure was not observed for the soy-pectin blend, which presented a different structure with significantly lower porosities than all other groups. The in vitro evaluation of these porous soy blends demonstrated that soy-alginate blends are advantageous over soy-gelatin blends and exhibited adequate cytocompatibility along with better cell infiltration and stability. These soy protein scaffolds may be potentially useful as a cellular/acellular platform for skin regeneration applications.

Novel porous soy protein-based blend structures for biomedical applications: Microstructure, mechanical, and physical properties.

Use of naturally derived materials for biomedical applications is steadily increasing. Soy protein has advantages over various types of natural proteins employed for biomedical applications due to its low price, nonanimal origin, and relatively long storage time and stability. In the current study, blends of soy protein with other polymers (gelatin, alginate, pectin, polyvinyl alcohol, and polyethylene glycol) were developed and studied. The mechanical tensile properties of dense films were studied in order to select the best secondary polymer for porous three-dimensional structures. The porous soy-gelatin and soy-alginate structures were then studied for physical properties, degradation behavior, and microstructure. The results show that these blends can be assembled into porous three-dimensional structures by combining chemical crosslinking with freeze-drying. The soy-alginate blends are advantageous over soy-gelatin blends, demonstrated better stability, and degradation time along with controlled swelling behavior due to more effective crosslinking and higher water uptake than soy-gelatin blends. Water vapor transmission rate experiments showed that all porous blend structures were in the desired range for burn treatment [2000-2500 g/(m(2) d)] and can be controlled by the crosslinking process. We conclude that these novel porous three-dimensional structures have a high potential for use as scaffolds for tissue engineering, especially for skin regeneration applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1109-1120, 2016.

Drug delivery from gelatin-based systems.

INTRODUCTION: Carriers for controlled drug release offer many advantages compared with conventional dosage forms. Gelatin has been investigated extensively as a drug delivery carrier, due to its properties and history of safe use in a wide range of medical applications. AREAS COVERED: Gelatin was shown to be versatile due to its intrinsic features that enable the design of different carrier systems, such as microparticles and nanoparticles, fibers and even hydrogels. Gelatin microparticles can serve as vehicles for cell amplification and for delivery of large bioactive molecules, whereas gelatin nanoparticles are better suited for intravenous delivery or for drug delivery to the brain. Gelatin fibers contain a high surface area-to-volume ratio, whereas gelatin hydrogels can trap molecules between the polymer's crosslink gaps, allowing these molecules to diffuse into the blood stream. Another interesting area is the combination of tissue bioadhesive-based gelatin with controlled drug release for pain management and wound healing. EXPERT OPINION: The modification of gelatin and its combinations with other biomaterials have demonstrated the flexibility of these systems and can be employed for meeting the challenges of finding ideal carrier systems that enable specific, targeted and controlled release in response to demands in the body.

Biodegradable soy wound dressings with controlled release of antibiotics: Results from a guinea pig burn model.

There is growing interest in the development of biodegradable materials from renewable biopolymers, such as soy protein, for biomedical applications. Soy protein is a major fraction of natural soybean and has the advantages of being economically competitive, biodegradable and biocompatible. It presents good water resistance as well as storage stability. In the current study, homogenous antibiotic-loaded soy protein films were cast from aqueous solutions. The antibiotic drug gentamicin was incorporated into the films in order to inhibit bacterial growth, and thus prevent or combat infection, upon its controlled release to the surrounding tissue. The current in vivo study of the dressing material in contaminated deep second-degree burn wounds in guinea pigs (n=20) demonstrated its ability to accelerate epithelialization with 71% epithelial coverage compared to an unloaded format of the soy material (62%) and a significant improved epithelial coverage as compared to the conventional dressing material (55%). Our new platform of antibiotic-eluting wound dressings is advantageous over currently used popular dressing materials that provide controlled release of silver ions, due to its gentamicin release profile, which is safer. Another advantage of our novel concept is that it is based on a biodegradable natural polymer and therefore does not require bandage changes and offers a potentially valuable and economic approach for treating burn-related infections.

Hybrid wound dressings with controlled release of antibiotics: Structure-release profile effects and in vivo study in a guinea pig burn model.

Over the last decades, wound dressings have evolved from a crude traditional gauze dressing to tissue-engineered scaffolds. Many types of wound dressing formats are commercially available or have been investigated. We developed and studied hybrid bilayer wound dressings which combine a drug-loaded porous poly(dl-lactic-co-glycolic acid) top layer with a spongy collagen sublayer. Such a structure is very promising because it combines the advantageous properties of both layers. The antibiotic drug gentamicin was incorporated into the top layer for preventing and/or defeating infections. In this study, we examined the effect of the top layer's structure on the gentamicin release profile and on the resulting in vivo wound healing. The latter was tested on a guinea pig burn model, compared to the neutral non-adherent dressing material Melolin® (Smith & Nephew) and Aquacel® Ag (ConvaTec). The release kinetics of gentamicin from the various studied formulations exhibited burst release values between 8% and 38%, followed by a drug elution rate that decreased with time and lasted for at least 7 weeks. The hybrid dressing, with relatively slow gentamicin release, enabled the highest degree of wound healing (28%), which is at least double that obtained by the other dressing formats (8-12%). It resulted in the lowest degree of wound contraction and a relatively low amount of inflammatory cells compared to the controls. This dressing was found to be superior to hybrid wound dressings with fast gentamicin release and to the neat hybrid dressing without drug release. Since this dressing exhibited promising results and does not require frequent bandage changes, it offers a potentially valuable concept for treating large infected burns.

Poly(methyl methacrylate) particles for local drug delivery using shock wave lithotripsy: In vitro proof of concept experiment.

To leverage current local drug delivery systems methodology, there is vast use of polymeric particles serving as drug carriers to assure minimal invasive therapy with little systemic distribution of the released drug. There is an increasing interest in poly(methyl methacrylate) (PMMA) serving as carriers in drug delivery. The study aims to develop PMMA carriers for localized drug delivery and release system, combining innovative biomaterial technology and shock wave lithotripsy (SWL), and to study the effect of SWL on various concentrations of PMMA particles. We prepared PMMA particles that contain horseradish peroxidase (HRP) using a double emulsion technique, and investigated the mechanism of in vitro drug release from the carriers following exposure to SWL. We investigated the correlation between production method modifications, concentrations of the carriers subjected to SWL, and shock wave patterns. We successfully produced PMMA particles as drug carriers and stimulated the release of their contents by SWL; their polymeric shell can be shattered externally by SWL treatment, leading to release of the encapsulated drug. HRP enzyme activity was maintained following the encapsulation process and exposure to high dose of SWL pulses. Increased shock wave number results in increased shattering and greater fragmentation of PMMA particles. The results demonstrate a dose-response release of HRP; quantitation of the encapsulated HRP from the carriers rises with the number of SWL. Moreover, increased concentration of particles subjected to the same dose of SWL results in a significant increase of the total HRP release. Our research offers novel technique and insights into new, site-specific drug delivery and release systems.

Pore size distribution of bioresorbable films using a 3-D diffusion NMR method.

Pore size distribution (PSD) within porous biomaterials is an important microstructural feature for assessing their biocompatibility, longevity and drug release kinetics. Scanning electron microscopy (SEM) is the most common method used to obtain the PSD of soft biomaterials. The method is highly invasive and user dependent, since it requires fracturing of the sample and then considers only the small portion that the user had acquired in the image. In the current study we present a novel nuclear magnetic resonance (NMR) method as an alternative method for estimation of PSD in soft porous materials. This noninvasive 3-D diffusion NMR method considers the entire volume of the specimen and eliminates the user's need to choose a specific field of view. Moreover, NMR does not involve exposure to ionizing radiation and can potentially have preclinical and clinical uses. The method was applied on four porous 50/50 poly(dl-lactic-co-glycolic acid) bioresorbable films with different porosities, which were created using the freeze-drying of inverted emulsions technique. We show that the proposed NMR method is able to address the main limitations associated with SEM-based PSD estimations by being non-destructive, depicting the full volume of the specimens and not being dependent on the magnification factor. Upon comparison, both methods yielded a similar PSD in the smaller pore size range (1-25µm), while the NMR-based method provided additional information on the larger pores (25-50µm).

Effect of hemostatic agents on properties of gelatin-alginate soft tissue adhesives.

Lacerations and traumatic wounds are considered to be among the most prevalent scenarios encountered in hospitals and emergency rooms. Reattachment of the lacerated soft tissue edges is traditionally performed using sutures. Use of tissue adhesives, i.e. substances that have the ability to firmly attach lacerated tissues back together, has raised interest as an alternative, due to several advantages. Novel tissue adhesives based on the natural polymers gelatin and alginate, and cross-linked by carbodiimide (EDC), were recently developed by our research group. In the current research, two types of hemostatic agents, tranexamic acid and kaolin, were loaded into our gelatin-alginate bioadhesive, in order to improve the adhesion abilities in the hemorrhagic environment of the wound. Their effects on the ex vivo adherence properties, physical properties, and biocompatibility were investigated. Incorporation of kaolin significantly improved the ex vivo bonding strength of the gelatin-alginate-EDC bioadhesives through a combination of three physical mechanisms and decreased the swelling ratio without affecting weight loss. In contradiction, incorporation of tranexamic acid into the bioadhesive formulation resulted in a lower ex vivo bonding strength and a higher swelling ratio and weight loss, probably due to reduced efficiency of the cross-linking reaction between the molecules of the natural polymers and the cross-linking agent EDC. The hemostatic agent-loaded bioadhesives showed good biocompatibility when tested in vitro on fibroblast cells. This research clearly shows that the incorporation of kaolin in our gelatin-alginate tissue adhesives may be a very promising novel approach for improving the bonding strength and physical properties of the tissue adhesives for use in hemorrhagic environments.

Effect of calcium phosphate-based fillers on the structure and bonding strength of novel gelatin-alginate bioadhesives.

Interest in soft and hard tissue adhesives as alternatives for conventional wound closing and bone fixation applications has increased in recent decades as a result of numerous possible advantages such as better comfort and lower cost. A novel bioadhesive based on the natural polymers GA has recently been developed and studied in our laboratory. Hydroxyapatite and tricalcium phosphate are two bioactive ceramics known for their ability to enhance bone regeneration. In the current study, these two bioactive fillers were incorporated into the bioadhesive at concentrations of 0.125, 0.25 and 0.5% w/v, and their effects on the resulting adherence properties to soft and hard tissues were studied. Porcine skin and cortical portions of bovine femurs were used as soft and hard tissue specimens, respectively. The bonding strength was evaluated using an Instron universal testing machine in tensile mode, and the microstructure analysis was based on environmental scanning electron microscope observations. Both bioactive fillers were found to have a reinforcing effect on the adhesives, significantly improving their adhesion to soft tissues in certain concentrations. The best bonding strength results were obtained for 0.25% hydroxyapatite and 0.5% w/v tricalcium phosphate-18.1 ± 4.0 and 15.2 ± 2.6 kPa, respectively, compared with 8.4 ± 2.3 kPa for adhesive with no fillers. The improved adherence is probably related to the stiffness of the insoluble hydroxyapatite and tricalcium phosphate particles which reinforce the adhesive. These particles can clearly be observed in the environmental scanning electron microscope analysis. The potential of these fillers to increase the bonding strength of the adhesive to hard tissues was also demonstrated. Hydroxyapatite and tricalcium phosphate thus improve our new gelatin-alginate bioadhesives, which can be used for both soft and hard tissue adhesive applications.