Silk protein-biomaterial wound dressings with epidermal growth factor (EGF) and silver sulfadiazine were studied with a cutaneous excisional mouse wound model. Three different material designs (silk films, lamellar porous silk films, electrospun silk nanofibers) and two different drug functionalization techniques (drug coatings or drug loading into the materials) were studied to compare wound healing responses. Changes in wound size and histological assessments of wound tissues over time confirmed that functionalized silk biomaterial wound dressings increased wound healing rate, including reepithelialization, dermis proliferation, collagen synthesis, epidermal differentiation into hair follicles and sebaceous glands, and reduced scar formation, when compared to air-permeable Tegaderm™ tape (3M) (− control) and a commercially sold wound dressing (Tegaderm™ Hydrocolloid dressing) (+ control). All silk biomaterials studied were effective for wound healing, while the porous features of the silk biomaterials (lamellar porous films and electrospun nanofibers) and the incorporation of EGF/silver sulfadiazine, via drug loading or coating, provided the most rapid wound healing responses. This systematic approach to evaluate functionalized silk biomaterial wound dressings demonstrates a useful strategy to select formulations for further study towards new treatment options for chronic wounds.

Postoperative peritoneal adhesions can cause pelvic pain, infertility, and potentially lethal bowel obstruction. We have designed and synthesized injectable hydrogels that are formed by mixing hydrazide-modified hyaluronic acid (HA) with aldehyde-modified versions of cellulose derivatives such as carboxymethylcellulose (CMC), hydroxypropylmethyl cellulose (HPMC), and methyl cellulose (MC). Gelation of these hydrogels occurred in less than 1 min, and had higher shear moduli than that of HA-HA gel (HAX). Hydrogels degraded in the presence of hyaluronidase in vitro, with HA-MC and HA-HPMC degrading more slowly than HAX and HA-CMC. The aldehyde-modified cellulose derivatives showed dose-dependent mild-to-moderate cytotoxicity to mesothelial cells and macrophages in vitro, but all were biocompatible in the murine peritoneum, causing no adhesions for 3 weeks. All the cellulose-derived gels showed efficacy in reducing the area of adhesion formation in a rabbit sidewall defect-bowel abrasion model.

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Non-invasive approaches to assess tissue function could improve significantly current methods to diagnose diseases and optimize engineered tissues. In this study, we describe a two-photon excited fluorescence microscopy approach that relies entirely on endogenous fluorophores to dynamically quantify functional metabolic readouts from individual cells within three-dimensional engineered tissues undergoing adipogenic differentiation over six months. Specifically, we employ an automated approach to analyze 3D image volumes and extract a redox ratio of metabolic cofactors. We identify a decrease in redox ratio over the first two months of culture that is associated with stem cell differentiation and lipogenesis. In addition, we demonstrate that the presence of endothelial cells facilitate greater cell numbers deeper within the engineered tissues. Since traditional assessments of engineered tissue structure and function are destructive and logistically intensive, this non-destructive, label-free approach offers a potentially powerful high-content characterization tool for optimizing tissue engineering protocols and assessing engineered tissue implants.

To improve the appeal of frozen baked foods upon heating, we have encapsulated flavor oil in complex coacervate microcapsules using gelatin and gum Arabic. Variation of polyion concentrations and homogenization rate affected particle morphology, size distribution, and oil release upon heating. Release of the oil from formulations was determined by a simple spectroscopic method based on separation of oil labeled with a lipophilic dye from unaffected particles. When heated to 100 degrees C or higher, univesicular microcapsules (prepared with a lower homogenization rate) released almost all of the encapsulated oil, while multivesicular microcapsules (produced by high homogenization rates) resulted had lesser degrees of release. The oil remained encapsulated during 4 weeks of storage at 4 and -20 degrees C (freezing and thawing) but was released by exposure to 100 mM NaCl at room temperature. When particles were cooled after releasing their oil content, the oil was re-encapsulated.

Background: Sustained release of local anesthetics is frequently associated with myotoxicity. The authors investigated the role of particulate delivery systems and of the pattern of drug release in causing myotoxicity.Methods: Rats were given sciatic nerve blocks with bupivacaine solutions, two types of bupivacaine-containing microparticles (polymeric microspheres and lipid-protein-sugar particles), or blank particles with or without bupivacaine in the carrier fluid. Myotoxicity was scored in histologic sections of the injection sites. Bupivacaine release kinetics from the particles were measured. Myotoxicity of a range of bupivacaine concentrations from exposures up to 3 weeks was assessed in C2C12 myotubes, with or without microparticles.Results: Both types of bupivacaine-loaded microparticles, but not blank particles, were associated with myotoxicity. Whereas 0.5% bupivacaine solution caused little myotoxicity, a concentration of bupivacaine that mimicked the amount of bupivacaine released initially from particles caused myotoxicity. Local anesthetics showed both concentration and time-dependent myotoxicity in C2C12s. Importantly, even very low concentrations that were nontoxic over brief exposures became highly toxic after days or weeks of exposure. The presence of particles did not increase bupivacaine myotoxicity in vitro but did in vivo. Findings applied to both particle types.Conclusions: Whereas the release vehicles themselves were not myotoxic, both burst and extended release of bupivacaine were. A possible implication of the latter finding is that myotoxicity is an inevitable concomitant of sustained release of local anesthetics. Particles, and perhaps other vehicles, may enhance local toxicity through indirect mechanisms.

Current approaches to develop skin equivalents often only include the epidermal and dermal components. Yet, full thickness skin includes the hypodermis, a layer below the dermis of adipose tissue containing vasculature, nerves and fibroblasts, necessary to support the epidermis and dermis. In the present study, we developed a full thickness skin equivalent including an epidermis, dermis and hypodermis that could serve as an in vitro model for studying skin development, disease or as a platform for consumer product testing as a means to avoid animal testing. The full thickness skin equivalent was easy to handle and was maintained in culture for greater than 14 days while expressing physiologically relevant morphologies of both the epidermis and dermis, as seen by keratin 10, collagen I and collagen IV expression. The skin equivalent produced glycerol and leptin, markers of adipose tissue metabolism. This work serves as a foundation for our understanding of some of the necessary factors needed to develop a stable, functional model of full-thickness skin.

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