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Skin-on-a-chip models provide physiologically relevant platforms for studying diseases and drug evaluation, replicating the native skin structures and functions more accurately than traditional 2D or simple 3D cultures. However, challenges remain in creating models suitable for microneedling applications and monitoring, as well as developing skin cancer models for analysis and targeted therapy. Here, we developed a human skin/skin cancer-on-a-chip platform within a microfluidic device using bioprinting/bioengineering techniques. The fabricated skin models include vascular, dermal, and epidermal layers, demonstrating increased functionalities and maturation of dermal (Collagen I & Fibronectin for 7 days) as well as epidermal (Filaggrin & Keratin 10, 14, and 19 at the air-liquid interface (ALI) for 21 days) layers. Histological analysis confirmed the formation of a differentiated epidermis and ridges at the dermal-epidermal junction in our model, closely resembling native skin tissue. Melanoma cells were embedded approximately 400 μm beneath the epidermis to simulate tumor invasion into the dermis. The platform was further used to test doxorubicin (DOX)-loaded gelatin methacryloyl (GelMA) microneedles (MNs) for localized transdermal drug delivery targeting melanoma. The DOX-loaded MNs penetrated uniformly to a depth of approximately 600 μm, effectively reaching the melanoma cells. Drug delivery via MNs demonstrated significantly higher efficiency than diffusion through media flow, confirming the practicality and robustness of the proposed model for future therapeutic applications.

The use of hydrogels for tissue engineering and regenerative medicine has gained significant attention due to their biocompatibility, versatility, and ability to mimic the extracellular matrix of tissues. In this study, we investigated the potential of nano-hydroxyapatite (nHAp)-based hydrogels by using simply modified gelatin and hyaluronic acid for bone tissue engineering as means to use a 3D bioink with in situ manner. First, we confirmed the biocompatibility and cell proliferation rate of the hydrogels by encapsulating human adipose-derived stem cells (hASCs) within the hydrogel matrix. We observed that the addition of nHAp to the hydrogel matrix promoted cell proliferation and enhanced 3D cell organization. Next, we evaluated the osteogenic differentiation potential of hASCs-laden hydrogel through alkaline phosphatase (ALP) activity and alizarin red s staining. The results showed that the hydrogel-containing nHAp group had the highest ALP activity and mineralization, indicating its potential for inducing bone formation. In vivo studies using a rat subcutaneous implantation model and a rat calvarial defect model further confirmed the ability of nHAp-based hydrogels to promote bone formation. Overall, results demonstrate the potential of nHAp-based in situ hydrogels for bone tissue engineering, highlighting their potential as a promising 3D bioink material with enhanced bone regeneration.

Abstract Messenger RNA (mRNA) therapy is the intracellular delivery of mRNA to produce desired therapeutic proteins. Developing strategies for local mRNA delivery is still required where direct intra‐articular injections are inappropriate for targeting a specific tissue. The mRNA delivery efficiency depends on protecting nucleic acids against nuclease‐mediated degradation and safe site‐specific intracellular delivery. Herein, novel mRNA‐releasing matrices based on RGD‐moiety‐rich gelatin methacryloyl (GelMA) microporous annealed particle (MAP) scaffolds are reported. GelMA concentration in aerogel‐based microgels (µgels) produced through a microfluidic process, MAP stiffnesses, and microporosity are crucial parameters for cell adhesion, spreading, and proliferation. After being loaded with mRNA complexes, MAP scaffolds composed of 10% GelMA µgels display excellent cell viability with increasing cell infiltration, adhesion, proliferation, and gene transfer. The intracellular delivery is achieved by the sustained release of mRNA complexes from MAP scaffolds and cell adhesion on mRNA‐releasing scaffolds. These findings highlight that hybrid systems can achieve efficient protein expression by delivering mRNA complexes, making them promising mRNA‐releasing biomaterials for tissue engineering.

The tumor microenvironment consists of diverse, complex etiological factors. The matrix component of pancreatic ductal adenocarcinoma (PDAC) plays an important role not only in physical properties such as tissue rigidity but also in cancer progression and therapeutic responsiveness. Although significant efforts have been made to model desmoplastic PDAC, existing models could not fully recapitulate the etiology to mimic and understand the progression of PDAC. Here, two major components in desmoplastic pancreatic matrices, hyaluronic acid- and gelatin-based hydrogels, are engineered to provide matrices for tumor spheroids composed of PDAC and cancer-associated fibroblasts (CAF). Shape analysis profiles reveals that incorporating CAF contributes to a more compact tissue formation. Higher expression levels of markers associated with proliferation, epithelial to mesenchymal transition, mechanotransduction, and progression are observed for cancer-CAF spheroids cultured in hyper desmoplastic matrix-mimicking hydrogels, while the trend can be observed when those are cultured in desmoplastic matrix-mimicking hydrogels with the presence of transforming growth factor-β1 (TGF-β1). The proposed multicellular pancreatic tumor model, in combination with proper mechanical properties and TGF-β1 supplement, makes strides in developing advanced pancreatic models for resembling and monitoring the progression of pancreatic tumors, which could be potentially applicable for realizing personalized medicine and drug testing applications.

Multiple diagnostic modalities are urgently needed to identify early-stage kidney diseases. Various molecules have been investigated; however, most studies have focused on identifying specific biomarkers in urine. Considering that assessing the symmetrical dimethylarginine (SDMA) plasma concentration is more suitable as an early diagnostic test for chronic kidney disease (CKD) in routine veterinary practice, we aimed to investigate the clinical usefulness of plasma neutrophil gelatinase-associated lipocalin (pNGAL) and plasma kidney injury molecule-1 (pKIM-1) concentrations for CKD detection in small-breed dogs. Through a retrospective analysis, we found that numerous clinicopathological data showed a log-normal distribution, even when they satisfied normality tests. Moreover, the log-transformed pNGAL and pKIM-1 concentrations successfully identified CKD International Renal Interest Society (IRIS) stages 1–4 and the risk group with underlying CKD risk factors. Correlation analysis and group comparison of other factors confirmed the possibility of using these two biomarkers for detecting the CKD risk group and IRIS stage 1. Receiver operating characteristic curve analysis revealed that the diagnostic accuracy for discriminating the risk group was superior in the order of pKIM-1, pNGAL, SDMA, and serum creatinine levels. In conclusion, these results suggest that pKIM-1 and pNGAL are possible early or quantifiable markers of insignificant CKD or can be at least used as an adjunct with traditional indicators.

In this study, using Illumina sequencing, we sequenced first the complete mitochondrial genome (mitogenome) of two deep-sea eels, Histiobranchus bathybius and Simenchelys parasitica, collected from the East Mariana Basin in the Western Pacific Ocean. The complete length of the H. bathybius and S. parasitica mitogenomes were 16,696 and 16,687 bp, respectively, each containing 37 genes (13 protein-coding genes, 22 tRNA genes, and 2 ribosomal RNA genes). To enhance the accuracy of the identification of H. bathybius and S. parasitica, we performed a phylogenetic analysis of multiple deep-sea eels based on the mitochondrial DNA gene (cytochrome c oxidase subunit I [COI]) using the maximum likelihood method. Our phylogenetic tree analysis confirmed that the specimens collected in this study are congeneric species of H. bathybius and S. parasitica reported in previous studies. Based on these results, we report the first complete mitogenomes of H. bathybius and S. parasitica and a new record for the two species in the East Mariana Basin.

Blood loss by hemorrhaging wounds accounts for over one-third of ∼5 million trauma fatalities worldwide every year. If not controlled in a timely manner, exsanguination can take lives within a few minutes. Developing new biomaterials that are easy to use by non-expert patients and promote rapid blood coagulation is an unmet medical need. Here, biocompatible, and biodegradable microneedle arrays (MNAs) based on gelatin methacryloyl (GelMA) biomaterial hybridized with silicate nanoplatelets (SNs) are developed for hemorrhage control. The SNs render the MNAs hemostatic, while the needle-shaped structure increases the contact area with blood, synergistically accelerating the clotting time from 11.5 min to 1.3 min in vitro. The engineered MNAs reduce bleeding by ∼92% compared with the untreated injury group in a rat liver bleeding model. SN-containing MNAs outperform the hemostatic effect of needle-free patches and a commercial hemostat in vivo via combining micro- and nanoengineered features. Furthermore, the tissue adhesive properties and mechanical interlocking support the suitability of MNAs for wound closure applications. These hemostatic MNAs may enable rapid hemorrhage control, particularly for patients in developing countries or remote areas with limited or no immediate access to hospitals.

Abstract Indocyanine green (ICG), glucose oxidase (GOx), and copper(II) sulfate (Cu)‐installed hybrid gel based on organic nanorod (cellulose nanocrystal [CNC]) and inorganic nanodisk (Laponite [LAP]) was developed to perform a combination of starvation therapy (ST), chemodynamic therapy (CDT), and photothermal therapy (PTT) for localized cancers. A hybrid CNC/LAP network with a nematic phase was designed to enable instant gelation, controlled viscoelasticity, syringe injectability, and longer in vivo retention. Moreover, ICG was introduced into the CNC/LAP gel system to induce hyperthermia of tumor tissue, amplifying the CDT effect; GOx was used for glucose deprivation (related to the Warburg effect); and Cu was introduced for hydroxyl radical generation (based on Fenton‐like chemistry) and cellular glutathione (GSH) degradation in cancer cells. The ICG/GOx/Cu‐installed CNC/LAP gel in combination with near‐infrared (NIR) laser realized improved antiproliferation, cellular reactive oxygen species (ROS) generation, cellular GSH degradation, and apoptosis induction in colorectal cancer (CT‐26) cells. In addition, local injection of the CNC/ICG/GOx/Cu/LAP gel into the implanted CT‐26 tumor while irradiating it with NIR laser provided strong tumor growth suppression effects. In conclusion, the designed hybrid nanorod/nanodisk gel network can be efficiently applied to the local PTT/ST/CDT of cancer cells.

Abstract Aerogel‐based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol‐gel, aging, drying, and self‐assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic‐based technologies and 3D printing can be combined with aerogel‐based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel‐based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels.

Abstract Developing theranostic devices to detect bleeding and effectively control hemorrhage in the prehospital setting is an unmet medical need. Herein, an all‐in‐one theranostic platform is presented, which is constructed by sandwiching silk fibroin (SF) between two silver nanowire (AgNW) based conductive electrodes to non‐enzymatically diagnose local bleeding and stop the hemorrhage at the wound site. Taking advantage of the hemostatic property of natural SF, the device is composed of a shape‐memory SF sponge, facilitating blood clotting, with ≈82% reduction in hemostatic time in vitro as compared with untreated blood. Furthermore, this sandwiched platform serves as a capacitive sensor that can detect bleeding and differentiate between blood and other body fluids (i.e., serum and water) via capacitance change. In addition, the AgNW electrode endows anti‐infection efficiency against Escherichia coli and Staphylococcus aureus. Also, the device shows excellent biocompatibility and gradually biodegrades in vivo with no major local or systemic inflammatory responses. More importantly, the theranostic platform presents considerable hemostatic efficacy comparable with a commercial hemostat, Dengen, in rat liver bleeding models. The theranostic platform provides an unexplored strategy for the intelligent management of hemorrhage, with the potential to significantly improve patients' well‐being through the integration of diagnostic and therapeutic capabilities.

Owing to the constant wind generated by the vast ocean, energy production from offshore wind farms (OWFs) plays an important role in the expansion of renewable energy. However, areas close to large wind farms are often left unutilized, and aquaculture farmers find it difficult to efficiently utilize these unoccupied spaces due to limited information showing the feasibility of utilization of OWFs as potential scallop culture sites. To analyze whether the two scallop species Zhikong scallop (Chlamys farreri) and bay scallop (Argopecten irradians) can be grown at OWFs of Gochang and Buan, Jeollabuk-do, Republic of Korea, the growth characteristics of the two scallop species were analyzed and compared with those grown at the Tongyeong Megacosm Test Station. The results clearly showed that the growth of scallops at the OWF was significantly lower with respect to the shell lengths, height, width, and weight, compared to those grown at the megacosm station. However, scallops grown at the OWF still showed consistent growth in parallel with those grown at the megacosm test station. Yet, there was a species-specific mortality rate between the two sites. In addition, our results suggest that temperature may be a key determinant of the growth of C. farreri and A. irradians. Overall, this study contributes to establishing a foundation for the stable and continuous farming of marine bivalves (e.g., clams, oysters, mussels, and scallops) in OWF areas.

The mammalian tissue extracellular matrix (ECM) has been used as a scaffold to facilitate the repair and reconstruction of numerous tissues. However, the material properties of decellularized ECM (dECM) from in vitro cell cultures and the effect of these properties on wound remodeling remain unclear. To elucidate its biological activity, we extracted dECM from human lung fibroblasts, fabricated it into a patch, and applied it to a full-thickness skin wound. The fibroblast-derived dECM (fdECM) maintained the content of collagen Ⅰ, collagen Ⅳ, and elastin, and the extraction process did not damage its critical growth factors. The fdECM-conjugated collagen patch (COL-fdECM) facilitated wound contraction and angiogenesis in the proliferative phase when applied to the in vivo full-thickness skin wound model. Moreover, the COL-fdECM treated wound showed increased regeneration of the epidermal barrier function, mature collagen, hair follicle, and subepidermal nerve plexus, suggesting qualitative skin remodeling. This therapeutic efficacy was similarly observed when applied to the diabetic ulcer model. fdECM was shown to help remodel the tissue by regulating fibroblast growth factors, matrix metalloproteinases, and tissue inhibitors of metalloproteinases via the p38 and ERK signaling pathways in an in vitro experiment for understanding the underlying mechanism. These results provide a biological basis for cell-derived ECM as a multi-functional biomaterial applicable to various diseases.

Abstract Background Increasing antibiotic resistance continues to focus on research into the discovery of novel antimicrobial agents. Due to its antimicrobial and wound healing-promoting activity, metal nanoparticles have attracted attention for dermatological applications. This study is designed to investigate the scope and bactericidal potential of zinc ferrite nanoparticles (ZnFe2O4 NPs), and the mechanism of anti-bacterial action along with cytocompatibility, hemocompatibility, and wound healing properties. Results ZnFe2O4 NPs were synthesized via a modified co-precipitation method. Structure, size, morphology, and elemental compositions of ZnFe2O4 NPs were analyzed using X-ray diffraction pattern, Fourier transform infrared spectroscopy, and field emission scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. In PrestoBlue and live/dead assays, ZnFe2O4 NPs exhibited dose-dependent cytotoxic effects on human dermal fibroblasts. In addition, the hemocompatibility assay revealed that the NPs do not significantly rupture red blood cells up to a dose of 1000 µg/mL. Bacterial live/dead imaging and zone of inhibition analysis demonstrated that ZnFe2O4 NPs showed dose-dependent bactericidal activities in various strains of Gram-negative and Gram-positive bacteria. Interestingly, NPs showed antimicrobial activity through multiple mechanisms, such as cell membrane damage, protein leakage, and reactive oxygen species generation, and were more effective against gram-positive bacteria. Furthermore, in vitro scratch assay revealed that ZnFe2O4 NPs improved cell migration and proliferation of cells, with noticeable shrinkage of the artificial wound model. Conclusions This study indicated that ZnFe2O4 NPs have the potential to be used as a future antimicrobial and wound healing drug.

BackgroundThere is widespread prejudice in veterinary medicine that gout does not occur in non-human mammalians. However, we recently discovered monosodium urate crystals in the synovial fluid obtained from a few dogs and a cat. Since it is the definitive and gold standard to diagnose gout, we report these cases as newly emerging diseases in companion animals.Case PresentationFour dogs and one cat were presented at our hospital because of lameness due to an unknown cause. Even after the routine examinations, including radiographic imaging, laboratory examination, and arthrocentesis, we were unable to find a clear cause of polyarthritis. However, we later discovered monosodium urate crystals in the synovial fluid of the animals, confirmed by polarized microscopy. In one of the two dogs treated with immunosuppressants, the disease relapsed, and the other did not show any symptoms for 3 months. The other two dogs were treated with xanthine oxidase inhibitor, where one died, and the other did not show any symptoms for 3 years. The cat was treated with drainage and intra-articular dexamethasone injection, but the disease recurred after 6 months.ConclusionThis is the first report to confirm that articular gout can occur in dogs and cats. Care must be taken not to neglect needle-shaped materials in the synovial fluid. Gout should also be included in the differential diagnosis of arthritis and further research is needed in these animals.

In this study, we document the first recorded range extension of the genus Synaphobranchus from the East Mariana Basin in the Western Pacific Ocean. We sequenced the complete mitochondrial (mt) genome of two deep-sea eels (Synaphobranchus brevidorsalis and S. affinis) collected in the East Mariana Basin in the Western Pacific Ocean. The complete mt genomes of S. brevidorsalis and S. affinis were 16,686 bp and 16,677 bp in length, respectively, and consisted of 13 protein-coding genes, 22 tRNA genes, and two rRNA genes. Molecular phylogenetic analysis of the two deep-sea eel species was performed, based on the mt cytochrome c oxidase subunit I (COI) gene using the maximum likelihood method. The molecular phylogenetic tree demonstrated that S. brevidorsalis and S. affinis were congeneric species of S. brevidorsalis and S. affinis reported in previous studies with bootstrap values of 100% and 100%, respectively. This is the first report on the complete mt genomes of S. brevidorsalis and S. affinis collected in the East Mariana Basin in the Western Pacific Ocean. Overall, our study highlights the potential of molecular approaches in identifying species diversity and distribution in the Western Pacific Ocean.

To date, 19 species of spiny lobsters from the genus Panulirus have been discovered, of which only P. japonicus, P. penicilatus, P. stimpsoni, and P. versicolor have been documented in South Korean waters. In this study, we aimed to identify and update the current list of spiny lobster species that inhabit South Korean waters based on the morphological features and the phylogenetic profile of cytochrome oxidase I (COI) of mitochondrial DNA (mtDNA). Spiny lobsters were collected from the southern and eastern coasts of Jeju Island, South Korea. Phylogenetic analyses were performed using neighbor-joining (NJ), maximum likelihood (ML), and Bayesian inference (BI) methods. The ML tree was used to determine the spiny lobster lineages, thereby clustering the 17 specimens collected in this study into clades A, B, C, and D, which were reciprocally monophyletic with P. japonicus, P. homarus homarus, P. longipes, and P. stimpsoni, respectively. These clades were also supported by morphological examinations. Interestingly, morphological variations, including the connected pleural and transverse groove at the third abdominal somite, were observed in four specimens that were genetically confirmed as P. japonicus. This finding is novel within the P. japonicus taxonomical reports. Additionally, this study updates the documentation of spiny lobsters inhabiting South Korean waters as P. longipes and P. homarus homarus were recorded for the first time in this region.

This Roadmap on drug delivery aims to cover some of the most recent advances in the field of materials for drug delivery systems (DDSs) and emphasizes the role that multifunctional materials play in advancing the performance of modern DDS _s in the context of the most current challenges presented. The Roadmap is comprised of multiple sections, each of which introduces the status of the field, the current and future challenges faced, and a perspective of the required advances necessary for biomaterial science to tackle these challenges. It is our hope that this collective vision will contribute to the initiation of conversation and collaboration across all areas of multifunctional materials for DDSs. We stress that this article is not meant to be a fully comprehensive review but rather an up-to-date snapshot of different areas of research, with a minimal number of references that focus upon the very latest research developments.

Postmenopausal obesity is becoming a serious global health concern. Soyasaponin Ab (SA) inhibits adipocyte differentiation; however, the preventive and therapeutic potential of SA in postmenopausal obesity has not been clearly established. Here, we investigated the anti-obesity effects of SA in postmenopausal obesity in vitro and in vivo. SA inhibited adipocytic differentiation of 3T3-L1 cells and reduced lipid accumulation and lipid droplet formation. Moreover, SA significantly decreased weight gain, adipocyte area, serum metabolic profiles in OVX mice. SA also inhibited the lipid metabolism-related factors but increased the thermoregulatory factors in both in vitro and in vivo. SA treatment further increased energy expenditure through beige fat activation. Overall, we found that SA effectively accelerated energy consumption by stimulating beige fat activation, even under estrogen-deficient conditions. Thus, SA treatment may be a promising strategy for the prevention of postmenopausal obesity by promoting weight loss, reducing fat accumulation, and improving obesity-related metabolic disorders.

Benthic habitat zonation is described from in situ observations and seabed photographs taken from the coastal area of Weno Island, Chuuk, Micronesia. Habitat groups, types, and boundaries are defined by visible substratum characteristics (i.e., in situ and by digital imaging of photo-quadrats along transect lines), and by cluster and ordination analyses using relative coverage percentage of identified classification categories. The statistical similarity between habitat groups is determined by Analysis of similarity (ANOSIM). Benthic habitat groups with significant influence on the determination of habitat type are isolated by the similarity percentage (SIMPER) test. In addition to the standard practices of using transect lines and collecting data in accordance with the already well-implemented and thoroughly-tested benthic habitat classification scheme for tropical reef monitoring, we applied simple statistics that enable comparative data interpretation. Our simple, repeatable methods provide a framework for benthic habitat-related monitoring research that allows the comparison of results across regions.

Two deep-sea eels collected from the East Mariana Basin in the western Pacific Ocean are described in this study. Based on their morphological features, two eel specimens were assumed to belong to the Gray cutthroat eel family, Synaphobranchidae. Mitochondrial DNA (mtDNA) genes have been widely used as genetic markers to identify fish species. To accurately identify the species of the two eel specimens, we sequenced the mitochondrial cytochrome c oxidase subunit I (COI) and 16S ribosomal RNA (16S rRNA) genes from the two eel specimens. The sequences from the specimens were 100% identical. The molecular phylogenetic tree confirmed that the two eel specimens were closely related to Synaphobranchus affinis with a bootstrap value of 100%. This is the first study to report new records of S. affinis from the East Mariana Basin in the western Pacific Ocean.

In this study, we investigated the reproductive pattern of the commercially and ecologically important species, Ostrea denelamellosa, to inform stock management strategies in South Korea. Prior to the reproduction experiment, the complete mitochondrial (mt) genome of the flat oyster, Ostrea denselamellosa, was analyzed using next-generation sequencing technology. Then, to determine the reproductive pattern of Ostrea denselamellosa, we investigated monthly changes in the gametogenesis, reproductive cycle, and sex ratio from January to October 2021 in females. The total length of the mt genome sequence of O. denselamellosa was 16,225 bp and contained 37 genes (13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes). Molecular phylogenetic comparison with 20 known species of Pteriomorphia showed that O. denselamellosa belongs to the family Ostreidae. In addition, O. denselamellosa clustered together with the O. denselamellosa Chinese strain, with a bootstrap value of 100%. Histological analysis indicated a discrepancy in gamete development of O. denselamellosa with synchronous maturation of oocytes and asynchronous development of spermatozoa in gonads. The spawning activity occurred between May and September with a temperature range gap of 6.5 °C. The spawning activity occurred from May when the temperature reached 16.7 °C until September when the temperature dropped below 23.2 °C. Furthermore, sex ratio bias was observed. This is the first study to report the complete mt genome sequence and examine the reproductive pattern in native O. denselamellosa in South Korea. Overall, these findings will help enhance the knowledge for the management and sustainable fishery of endangered oyster species including O. denselamellosa in the South Sea of Korea.

Abstract Endovascular embolization to treat vascular hemorrhage involves pushing coil‐shaped metal wires into the artery repeatedly until they are densely packed to slow the blood flow and clot. However, coil embolization is associated with high rebleeding rates, unpredictable economics and, most importantly, they rely on the patient's ability to make a clot. These issues are exacerbated when the patient is anticoagulated or coagulopathic. A novel bioengineered tantalum‐loaded nanocomposite hydrogel for gel embolic material (Ta‐GEM) that can be rapidly delivered using clinical catheters for instant hemostasis regardless of the coagulopathic state is reported. Ta‐GEM formulation is visible by most of the clinically available imaging modalities including ultrasound, computed tomography, magnetic resonance imaging, and fluoroscopy without significant artifact. In addition, Ta‐GEM can be retrieved, allowing temporary vascular occlusion, and it can be used to rescue cases of failed coil embolization. Ta‐GEM occlusion of first‐order arteries such as the renal artery and iliac artery in a swine model is found to be safe and durable; by 28 days, 75% of the injected Ta‐GEM in the arterial lumen is replaced by dense connective tissue. Altogether, this study demonstrates that Ta‐GEM has many advantages over the current technologies and has potential applications in clinical practice.

A 6-year-old female Maltese dog presented with a cervical mass without pain. The tumor was surrounded by a thick fibrous tissue and consisted of an osteoid matrix with osteoblasts and two distinct areas: a mesenchymal cell-rich lesion with numerous multinucleated giant cells and a chondroid matrix-rich lesion. The tumor cells exhibited heterogeneous protein expression, including a positive expression of vimentin, cytokeratin, RANKL, CRLR, SOX9, and collagen 2, and was diagnosed as extraskeletal osteosarcoma. Despite its malignancy, the dog showed no sign of recurrence or metastasis three months after the resection. Further analysis of the tumor cells revealed a high expression of proliferation- and metastasis-related biomarkers in the absence of angiogenesis-related biomarkers, suggesting that the lack of angiogenesis and the elevated tumor-associated fibrosis resulted in a hypoxic tumor microenvironment and prevented metastasis.

Porous calcium phosphate ceramics are used in orthopedic and craniofacial applications to treat bone loss, or in dental applications to replace missing teeth. The implantation of these materials, however, does not induce stem cell differentiation, so suitable additional materials such as porous calcium phosphate discs are needed to influence physicochemical responses or structural changes. Rabbit adipose-derived stem cells (ADSC) and mouse osteoblastic cells (MC3T3-E1) were evaluated in vitro by the MTT assay, semi-quantitative RT-PCR, and immunoblotting using cells cultured in medium supplemented with extracts from bioceramics, including calcium metaphosphate (CMP), hydroxyapatite (HA) and collagen-grafted HA (HA-col). In vivo evaluation of the bone forming capacity of these bioceramics in rat models using femur defects and intramuscular implants for 12 weeks was performed. Histological analysis showed that newly formed stromal-rich tissues were observed in all the implanted regions and that the implants showed positive immunoreaction against type I collagen and alkaline phosphatase (ALP). The intramuscular implant region, in particular, showed strong positive immunoreactivity for both type I collagen and ALP, which was further confirmed by mRNA expression and immunoblotting results, indicating that each bioceramic material enhanced osteogenesis stimulation. These results support our hypothesis that smart bioceramics can induce osteoconduction and osteoinduction in vivo, although mature bone formation, including lacunae, osteocytes, and mineralization, was not prominent until 12 weeks after implantation.