Reshapable polymeric hydrogel for controlled soft-tissue expansion: In vitro and in vivo evaluation

Tissue expansion is the process by which extra skin is generated using a device that applies pressure from underneath the skin. Over the course of weeks to months, stretching by this pressure creates a flap of extra tissue that can be used to cover a defect area or enclose a permanent implant. Conventional tissue expanders require a silicone shell inflated either by external injections of saline solution or air, or by internal osmotic pressure generated by a hydrophilic polymer. In this study, a shell-free tissue expander comprised only of a chemically cross-linked biocompatible polymeric hydrogel is developed. The cross-linked network of hydrophilic polymer provides for intrinsically controlled swelling in the absence of an external membrane. The new type of hydrogel expanders were characterized in vitro as well as in vivo using a rat-skin animal model. It was found that increasing the hydrophobic polyester content in the hydrogel reduced the swelling velocity to a rate and volume that eliminate the danger of premature swelling rupturing the sutured area. Additionally, increasing the crosslinking density resulted in enough mechanical strength of the hydrogel to allow for complete post-swelling removal, without the hydrogel cracking or crumbling. No systemic toxicity was noted with the expanders and histology showed the material to be highly biocompatible. These expanders have an advantage of tissue expansion without requiring an external silicone membrane, and thus, they can be cut or reshaped at the time of implantation for applications in small or physically constrained regions of the body

Reshapeable hydrogel tissue expander for ridge augmentation: Results of a series of successive insertions at the same intraoral site

Background Tissue expansion of oral mucosa prior to ridge augmentation promises to reduce the soft tissue exposure and improve the final intraoral bone graft density and volume. This study explored a novel, shapeable hydrogel tissue expander (HTE) in intraoral sites that had undergone previous expansion and surgery. Methods Nine beagle dogs had all premolar teeth extracted with alveolar bone reduction. At least 3 months healing followed before placing the hydrogels at 4 sites for each dog: maxilla and mandible, right and left. After 6 weeks of expansion, the expanded hydrogels were removed and measured for volume expansion and hydrogel condition. Punch biopsies were taken of the expanded oral mucosa. After healing of 3 months a second insertion of hydrogels was done at the same sites. Again, volume and hydrogel condition were recorded. Three dogs received ultrasound imaging of the expanding hydrogels upon the second insertion. Necropsy specimens were taken of both expanded and non‐expanded oral mucosa. Results Blood flow returned to that observed before insertion within two weeks after HTE insertion in both first and second insertions. First insertion resulted in linear gain of 8.13 mm, and second insertion showed a linear gain of 6.44 mm of oral mucosa. First and second insertion erupted at approximately 3% and 4% of the sites, respectively. There was no directional migration of the expanding hydrogels. Histology indicated little inflammatory reaction to any hydrogel implant. Conclusion Oral mucosa can be consistently and successfully expanded prior to bone graft for ridge augmentation even at sites with a history of prior surgeries

Baseline Biomechanical Properties of Epithelia prior to Tissue Expansion in Dogs

Background: Soft-tissue deficiencies pose a challenge in a variety of disease processes when the end result is exposure of underlying tissue. Although multiple surgical techniques exist, the transposition of tissue from one location to another can cause donor-site morbidity, long incisions prone to dehiscence, and poor patient outcomes as a result. Use of tissue expansion prior to grafting procedures has been shown to have success in increasing available soft tissue to aid in repairing wounds. However, the current tissue expanders have biomechanical limits to the extent and rate of expansion that usually exceeds the tissue capacity, leading to incisional dehiscence or expander extrusion. Understanding the baseline biomechanical properties of the tissue to be expanded would provide useful information regarding surgical protocol employed for a given anatomical location. Therefore, the aim of this study was to test and compare the baseline (preexpansion) biomechanical properties of different common expansion sites in dogs. Methods: Four samples measuring approximately 20 × 15 × 1 mm were harvested from 8 dogs. The samples were collected from the hard palate, alveolar mucosa, scalp, and chest of the animal and analyzed for stress, strain, maximum tangential stiffness, maximum tangential modulus, and tensile strength using a Texture Technologies TA.XT texture analyzer with corresponding biomechanical measurement software. Samples were compared as to their baseline biomechanical properties prior to any soft-tissue expansion. Histological sections of the samples were analyzed using hematoxylin eosin in an attempt to correlate the histological description to the biomechanical properties seen during testing. Summary statistics (mean, standard deviation, standard error, range) are reported for stress, strain, maximum tangential stiffness, maximum tangential modulus, and tensile strength and for the histological parameters by intraoral site. Analysis of variance was used to compare the biomechanical and histological parameters among the 4 locations while accounting for multiple measurements from each dog. Results: The scalp had significantly higher maximum stress (σmax) than chest, mucosa, and palate (P 0.63). Scalp site also had significantly higher maximum tangential modulus (ε) than chest, mucosa, and palate (P 0.17). The locations did not have significantly different maximum tangential stiffness (k; P = 0.72). Histologically, 2 separate patterns of collagen disruption were evident. Conclusion: Although different results were obtained than theorized, this study showed that the scalp had the greatest resiliency to expand prior to tearing, and the highest tangential modulus, with all sites having statistically similar modulus of elasticity. Based on this study, the scalp could be expanded more aggressively compared with the other sites

Mucosal Perfusion Preservation by a Novel Shapeable Tissue Expander for Oral Reconstruction

Background: There are few methods for expanding oral mucosa, and these often cause complications such as tissue necrosis and expander eruption. This study examines mucosal blood perfusion following insertion of a novel shapeable hydrogel tissue expander (HTE). The canine model used subgingival insertion of HTE following tooth extraction and alveolar bone reduction. The primary goal of this study was to gain understanding of epithelial perfusion and reparative responses of gingival mucosa during HTE expansion. Methods: Nine Beagle dogs underwent bilateral premolar maxillary and mandibular tooth extraction. Three to four months later, HTE-contoured inserts were implanted submucosally under the buccal surface of the alveolar ridge. After removal and following a 6- to 7-month period of healing, new HTE implants were inserted at the same sites. The area was assessed weekly for tissue perfusion and volume of expansion. Biopsies for histological analysis were performed at the time of expander removal. Results: Within 2 weeks following the second insertion, blood flow returned to baseline (defined as the values of perfusion measurements at the presurgery assessment) and remained normal until hydrogel full expansion and removal. Volume expansion analysis revealed that the hydrogel doubled in volume. Histological assessment showed no macrophage or inflammatory infiltration of the mucosa. No superficial fibrosis, decreased vascularity, or mucosal change was seen. Conclusion: Maintenance of adequate tissue perfusion is a clinically important aspect of tissue expander performance to reduce risk of device loss or injury to the patient, particularly for areas with a history of previous surgeries

Cytosolic SYT/SS18 Isoforms Are Actin-Associated Proteins that Function in Matrix-Specific Adhesion

SYT (SYnovial sarcoma Translocated gene or SS18) is widely produced as two isoforms, SYT/L and SYT/S, that are thought to function in the nucleus as transcriptional coactivators. Using isoform-specific antibodies, we detected a sizable pool of SYT isoforms in the cytosol where the proteins were organized into filamentous arrays. Actin and actin-associated proteins co-immunoprecipitated with SYT isoforms, which also co-sedimented and co-localized with the actin cytoskeleton in cultured cells and tissues. The association of SYT with actin bundles was extensive yet stopped short of the distal ends at focal adhesions. Disruption of the actin cytoskeleton also led to a breakdown of the filamentous organization of SYT isoforms in the cytosol. RNAi ablation of SYT/L alone or both isoforms markedly impaired formation of stress fibers and focal adhesions but did not affect formation of cortical actin bundles. Furthermore, ablation of SYT led to markedly impaired adhesion and spreading on fibronectin and laminin-111 but not on collagen types I or IV. These findings indicate that cytoplasmic SYT isoforms interact with actin filaments and function in the ability cells to bind and react to specific extracellular matrices

Cryptic species in a well-known habitat: applying taxonomics to the amphipod genus Epimeria (Crustacea, Peracarida)

Taxonomy plays a central role in biological sciences. It provides a communication system for scientists as it aims to enable correct identification of the studied organisms. As a consequence, species descriptions should seek to include as much available information as possible at species level to follow an integrative concept of ‘taxonomics’. Here, we describe the cryptic species Epimeria frankei sp. nov. from the North Sea, and also redescribe its sister species, Epimeria cornigera. The morphological information obtained is substantiated by DNA barcodes and complete nuclear 18S rRNA gene sequences. In addition, we provide, for the first time, full mitochondrial genome data as part of a metazoan species description for a holotype, as well as the neotype. This study represents the first successful implementation of the recently proposed concept of taxonomics, using data from highthroughput technologies for integrative taxonomic studies, allowing the highest level of confidence for both biodiversity and ecological research

Molecular marks for epigenetic identification of developmental and cancer stem cells

Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, namely, OCT4, NANOG, cMYC, SOX2, Klf4, and LIN28. The challenge to induce pluripotency is the insertion of four reprogramming genes (Oct4, Sox2, Klf4, and c-Myc) into the genome. There are always risks of silencing of these genes by epigenetic modifications in the host cells, particularly, when introduced through retroviral techniques. In this contribution, we will discuss some of the major discoveries on epigenetic modifications within the chromatin of various genes associated with cancer progression and cancer stem cells in comparison to normal development of stem cell. These modifications may be considered as molecular signatures for predicting disorders of development and for identifying disease states

Datasheet2_A dual osteoconductive-osteoprotective implantable device for vertical alveolar ridge augmentation.pdf

Repair of large oral bone defects such as vertical alveolar ridge augmentation could benefit from the rapidly developing additive manufacturing technology used to create personalized osteoconductive devices made from porous tricalcium phosphate/hydroxyapatite (TCP/HA)-based bioceramics. These devices can be also used as hydrogel carriers to improve their osteogenic potential. However, the TCP/HA constructs are prone to brittle fracture, therefore their use in clinical situations is difficult. As a solution, we propose the protection of this osteoconductive multi-material (herein called “core”) with a shape-matched “cover” made from biocompatible poly-ɛ-caprolactone (PCL), which is a ductile, and thus more resistant polymeric material. In this report, we present a workflow starting from patient-specific medical scan in Digital Imaging and Communications in Medicine (DICOM) format files, up to the design and 3D printing of a hydrogel-loaded porous TCP/HA core and of its corresponding PCL cover. This cover could also facilitate the anchoring of the device to the patient's defect site via fixing screws. The large, linearly aligned pores in the TCP/HA bioceramic core, their sizes, and their filling with an alginate hydrogel were analyzed by micro-CT. Moreover, we created a finite element analysis (FEA) model of this dual-function device, which permits the simulation of its mechanical behavior in various anticipated clinical situations, as well as optimization before surgery. In conclusion, we designed and 3D-printed a novel, structurally complex multi-material osteoconductive-osteoprotective device with anticipated mechanical properties suitable for large-defect oral bone regeneration.</p

Datasheet1_A dual osteoconductive-osteoprotective implantable device for vertical alveolar ridge augmentation.pdf

Repair of large oral bone defects such as vertical alveolar ridge augmentation could benefit from the rapidly developing additive manufacturing technology used to create personalized osteoconductive devices made from porous tricalcium phosphate/hydroxyapatite (TCP/HA)-based bioceramics. These devices can be also used as hydrogel carriers to improve their osteogenic potential. However, the TCP/HA constructs are prone to brittle fracture, therefore their use in clinical situations is difficult. As a solution, we propose the protection of this osteoconductive multi-material (herein called “core”) with a shape-matched “cover” made from biocompatible poly-ɛ-caprolactone (PCL), which is a ductile, and thus more resistant polymeric material. In this report, we present a workflow starting from patient-specific medical scan in Digital Imaging and Communications in Medicine (DICOM) format files, up to the design and 3D printing of a hydrogel-loaded porous TCP/HA core and of its corresponding PCL cover. This cover could also facilitate the anchoring of the device to the patient's defect site via fixing screws. The large, linearly aligned pores in the TCP/HA bioceramic core, their sizes, and their filling with an alginate hydrogel were analyzed by micro-CT. Moreover, we created a finite element analysis (FEA) model of this dual-function device, which permits the simulation of its mechanical behavior in various anticipated clinical situations, as well as optimization before surgery. In conclusion, we designed and 3D-printed a novel, structurally complex multi-material osteoconductive-osteoprotective device with anticipated mechanical properties suitable for large-defect oral bone regeneration.</p

Baseline Biomechanical Properties of Epithelia prior to Tissue Expansion in Dogs

Background:. Soft-tissue deficiencies pose a challenge in a variety of disease processes when the end result is exposure of underlying tissue. Although multiple surgical techniques exist, the transposition of tissue from one location to another can cause donor-site morbidity, long incisions prone to dehiscence, and poor patient outcomes as a result. Use of tissue expansion prior to grafting procedures has been shown to have success in increasing available soft tissue to aid in repairing wounds. However, the current tissue expanders have biomechanical limits to the extent and rate of expansion that usually exceeds the tissue capacity, leading to incisional dehiscence or expander extrusion. Understanding the baseline biomechanical properties of the tissue to be expanded would provide useful information regarding surgical protocol employed for a given anatomical location. Therefore, the aim of this study was to test and compare the baseline (preexpansion) biomechanical properties of different common expansion sites in dogs. Methods:. Four samples measuring approximately 20 × 15 × 1 mm were harvested from 8 dogs. The samples were collected from the hard palate, alveolar mucosa, scalp, and chest of the animal and analyzed for stress, strain, maximum tangential stiffness, maximum tangential modulus, and tensile strength using a Texture Technologies TA.XT texture analyzer with corresponding biomechanical measurement software. Samples were compared as to their baseline biomechanical properties prior to any soft-tissue expansion. Histological sections of the samples were analyzed using hematoxylin eosin in an attempt to correlate the histological description to the biomechanical properties seen during testing. Summary statistics (mean, standard deviation, standard error, range) are reported for stress, strain, maximum tangential stiffness, maximum tangential modulus, and tensile strength and for the histological parameters by intraoral site. Analysis of variance was used to compare the biomechanical and histological parameters among the 4 locations while accounting for multiple measurements from each dog. Results:. The scalp had significantly higher maximum stress (σmax) than chest, mucosa, and palate (P 0.63). Scalp site also had significantly higher maximum tangential modulus (ε) than chest, mucosa, and palate (P 0.17). The locations did not have significantly different maximum tangential stiffness (k; P = 0.72). Histologically, 2 separate patterns of collagen disruption were evident. Conclusion:. Although different results were obtained than theorized, this study showed that the scalp had the greatest resiliency to expand prior to tearing, and the highest tangential modulus, with all sites having statistically similar modulus of elasticity. Based on this study, the scalp could be expanded more aggressively compared with the other sites