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.

Modulation of scar tissue formation in injured nervous tissue cultivated on surface-engineered coralline scaffolds.

Following traumatic brain injury, there is no restoration of the lost nervous tissue, mainly due to the formation of a scar. One promising strategy to overcome this hurdle is grafting scaffolds that can disturb the scar blockade, enabling cell invasion into the wound. The aragonite skeleton of corals is useful scaffolds for testing this strategy, being supportive for neural cells in culture. The purpose of this work was to check if a contact between a coralline scaffold and an injured nervous tissue affects scar formation and if this effect can be regulated by engineering the scaffold's surface topology. To address that, hippocampal slices were cultivated on a coral skeleton having two distinct surface shapes: (1) intact skeleton pieces (ISP): porous, microrough surface; (2) grained skeleton (GS): nonporous, macrorough surface. On ISP, slices deformed by engulfing the scaffold's outer surface without penetrating the pores, yet, they preserved their coherence. By contrast, on GS slices were flat, but broken into interconnected small segments of tissue. In addition, whereas on ISP astrocytes were significantly more active and diffusely distributed, on GS reactive astrocytes tightened into a single <90 µm wide scar-like stripe at the slice's periphery. Hence, by grafting coralline scaffolds of predesigned surface roughness and porosity into brain wounds, control over scar tissue formation can be gained, providing an opportunity for cell migration and damage repair. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2295-2306, 2018.

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.

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.

Gelatin-alginate novel tissue adhesives and their formulation-strength effects.

Interest in tissue adhesives as alternatives for conventional wound-closing applications such as sutures and staples has increased in the last few decades due to numerous possible advantages, including less discomfort and lower cost. Novel tissue adhesives based on gelatin, with alginate as a polymeric additive and crosslinked by carbodiimide, were recently developed by our research group. The effects of the formulation parameters on the adhesives' function were investigated in the current study. We examined the effects of gelatin and alginate concentrations and their viscosities on the ability of the bioadhesives to bind soft tissues. The effect of the crosslinking agent's concentration was studied as well. A qualitative model describing these effects in terms of adherence mechanisms was developed. Our results show that the adherence properties of our new bioadhesives are achieved by a combination of two main mechanisms: mechanical interlocking and chemical adsorption. The former mechanism is probably more dominant. The polymer's molecular weight and concentration affect the mechanical interlocking through mobility and penetration ability, entanglement of the three-dimensional structure and crosslinking density. The crosslinking agent's concentration as well as the polymer's concentration affect the crosslinking density and contribute to higher strength, achieved through both the mechanical interlocking and the chemical adsorption mechanisms. Understanding the effects of the adhesives' components and their viscosities on the bonding strength enabled us to elucidate the bonding strength mechanisms. This can lead to proper selection of the adhesive formulation and may enable tailoring the bioadhesives to the desired applications.

Convergence among non-sister dendritic branches: an activity-controlled mean to strengthen network connectivity.

The manner by which axons distribute synaptic connections along dendrites remains a fundamental unresolved issue in neuronal development and physiology. We found in vitro and in vivo indications that dendrites determine the density, location and strength of their synaptic inputs by controlling the distance of their branches from those of their neighbors. Such control occurs through collective branch convergence, a behavior promoted by AMPA and NMDA glutamate receptor activity. At hubs of convergence sites, the incidence of axo-dendritic contacts as well as clustering levels, pre- and post-synaptic protein content and secretion capacity of synaptic connections are higher than found elsewhere. This coupling between synaptic distribution and the pattern of dendritic overlapping results in 'Economical Small World Network', a network configuration that enables single axons to innervate multiple and remote dendrites using short wiring lengths. Thus, activity-mediated regulation of the proximity among dendritic branches serves to pattern and strengthen neuronal connectivity.