Short-term results of endoscopic calcaneoplasty and retrocalcaneal bursectomy for insertional Achilles tendinopathy.

Although open surgery has traditionally been used as a surgical treatment for insertional Achilles tendinopathy, there is a possibility of serious complications (avulsion, scarring, contracture, sensory changes, and infection) due to the anatomical characteristics of the area. Endoscopic surgery has some advantages due to the smaller incision needed. The purpose of this study was to evaluate the effectiveness of endoscopic surgery in insertional Achilles tendinopathy. Twelve patients (15 feet) who underwent endoscopic surgery between 2015 and 2021 were included in this study. Clinical results were evaluated before and after surgery by visual analog scale (VAS) and, Ogilvie-Harris scores and complications. For radiological evaluation, the Fowler-Philip angle, and positive parallel pitch line were measured. VAS scores decreased from 7.6 preoperatively to 2.3 at the last postoperative follow-up, and Ogilvie-Harris values showed excellent results in 5 cases, good results in 8 cases, and fair results in 2 cases. In the radiographic results, there was no bone prominence above the Pavlov calcaneus pitch line in any case, and the Fowler-Philip angle decreased from an average of 57.5 degrees to 50.2 degrees. Only 1 patient underwent reoperation due to the recurrence of symptoms 33 months after the first surgery. After the second operation, the VAS score decreased to 3 points. No complications occurred. Endoscopic surgery is an effective and minimally invasive procedure, showing fewer complications and similar satisfaction as the open procedure. Therefore, it can be a good treatment option for patients with insertional Achilles tendinopathy as it provides the patient with a quick return to daily life.

3D printed multi-growth factor delivery patches fabricated using dual-crosslinked decellularized extracellular matrix-based hybrid inks to promote cerebral angiogenesis.

Generally, brain angiogenesis is a tightly regulated process, which scarcely occurred in the absence of specific pathological conditions. Delivery of exogenous angiogenic factors enables the induction of desired angiogenesis by stimulating neovasculature formation. However, effective strategies of mimicking the angiogenesis process with exogenous factors have not yet been fully explored. Herein, we develop a 3D printed spatiotemporally compartmentalized cerebral angiogenesis inducing (SCAI) hydrogel patch, releasing dual angiogenic growth factors (GFs), using extracellular matrix-based hybrid inks. We introduce a new hybrid biomaterial-based ink for printing patches through dual crosslinking mechanisms: Chemical crosslinking with aza-Michael addition reaction with combining methacrylated hyaluronic acid (HAMA) and vascular-tissue-derived decellularized extracellular matrix (VdECM), and thermal crosslinking of VdECM. 3D printing technology, a useful approach with fabrication versatility with customizable systems and multiple biomaterials, is adopted to print three-layered hydrogel patch with spatially separated dual GFs as outer- and inner-layers that provide tunable release profiles of multiple GFs and fabrication versatility. Consequently, these layers of the patch spatiotemporally separated with dual GFs induce excellent neovascularization in the brain area, monitored by label-free photoacoustic microscopy in vivo. The developed multi-GFs releasing patch may offer a promising therapeutic approach of spatiotemporal drugs releasing such as cerebral ischemia, ischemic heart diseases, diabetes, and even use as vaccines. STATEMENT OF SIGNIFICANCE: Effective strategies of mimicking the angiogenesis process with exogenous factors have not yet been fully explored. In this study, we develop a 3D printed spatiotemporally compartmentalized cerebral angiogenesis inducing (SCAI) hydrogel patch, releasing dual angiogenic growth factors (GFs) using extracellular matrix-based hybrid inks. We introduce a new hybrid biomaterial-based ink through dual crosslinking mechanisms: Chemical crosslinking with aza-Michael addition, and thermal crosslinking. 3D printing technology is adopted to print three-layered hydrogel patch with spatially separated dual GFs as outer- and inner-layers that provide tunable release profiles of multiple GFs and fabrication versatility. Consequently, these layers of the patch spatiotemporally separated with dual GFs induce excellent neovascularization in the brain area, monitored by photoacoustic microscopy in vivo.

Open Sciatic Nerve Decompression for Compartment Syndrome after Prolonged Lithotomy Position: A Case Report.

Background: Position-related compressive nerve injury is a frequently reported complication of the lithotomy position. In contrast, compartment syndrome-induced neuropathy after lithotomy with prolonged surgery is rare and prone to misdiagnosis. This case describes the successful open decompression of sciatic neuropathy due to compartment syndrome after a prolonged lithotomy position. Case presentation: A 56-year-old male patient complained of an abnormal sensation in the lower leg and difficulty in dorsiflexion and plantarflexion of the left foot and toes after laparoscopic anterior hepatic sectionectomy for 16 h in a lithotomy position. Physical examination revealed severe pain and paresthesia below the distal left thigh. In manual muscle test grading, dorsiflexion and plantarflexion of the left ankle and toes were classified as grade 1. Computed tomography and magnetic resonance imaging showed ischemic changes in the mid-thigh posterior muscles, and the sciatic nerve was severely swollen at the distal thigh, which was compressed by the proximal edge of the well-leg holder. After debridement of the necrotic tissue and decompression of the sciatic nerve, the pain subsided immediately, and the ankle and toe dorsiflexion motor function improved to grade 4. Conclusions: Most case reports of compressive neuropathy associated with the lithotomy position have been related to conservative treatment. However, if a lesion compressing the nerve is confirmed in an imaging study and the correlation with the patient's symptoms is evident, early surgical intervention can be an effective treatment method to minimize neurological deficits.

Modular assembly of bioprinted perfusable blood vessel and tracheal epithelium for studying inflammatory respiratory diseases.

In vitroorgan models allow for the creation of precise preclinical models that mimic organ physiology. During a pandemic of a life-threatening acute respiratory disease, an improved trachea model (TM) is required. We fabricated a modular assembly of the blood vessel and TMs using 3D bioprinting technology. First, decellularized extracellular matrix (dECM) were prepared using the porcine trachea and blood vessels. A trachea module was fabricated based on the tracheal mucosa-derived dECM and microporous membrane. Further, a blood vessel module was manufactured using the prepared vascular-tissue-derived dECM. By assembling each manufactured module, a perfusable vascularized TM simulating the interface between the tracheal epithelium and blood vessels was fabricated. This assembled model was manufactured with efficient performance, and it offered respiratory symptoms, such as inflammatory response and allergen-induced asthma exacerbation. These characteristics indicate the possibility of manufacturing a highly functional organ model that mimics a complex organ environment in the future.

3D cell aggregate printing technology and its applications.

Various cell aggregate culture technologies have been developed and actively applied to tissue engineering and organ-on-a-chip. However, the conventional culture technologies are labor-intensive, and their outcomes are highly user dependent. In addition, the technologies cannot be used to produce three-dimensional (3D) complex tissues. In this regard, 3D cell aggregate printing technology has attracted increased attention from many researchers owing to its 3D processability. The technology allows the fabrication of 3D freeform constructs using multiple types of cell aggregates in an automated manner. Technological advancement has resulted in the development of a printing technology with a high resolution of approximately 20 µm in 3D space. A high-speed printing technology that can print a cell aggregate in milliseconds has also been introduced. The developed aggregate printing technologies are being actively applied to produce various types of engineered tissues. Although various types of high-performance printing technologies have been developed, there are still some technical obstacles in the fabrication of engineered tissues that mimic the structure and function of native tissues. This review highlights the central importance and current technical level of 3D cell aggregate printing technology, and their applications to tissue/disease models, artificial tissues, and drug-screening platforms. The paper also discusses the remaining hurdles and future directions of the printing processes.

Clinical Outcomes of Total Hip Arthroplasty for Displaced Femoral Neck Fractures in Patients 80 Years of Age and Older Selected by Clinical Frailty Score.

PURPOSE: The utility of total hip arthroplasty (THA) for the treatment of displaced femoral neck fractures in elderly patients (≥80 years of age) remains controversial as a patient's general condition is an essential factor impacting recovery. This study aims to determine if THA is a valuable option for appropriately selected elderly patients. MATERIALS AND METHODS: All patients underwent cementless THA using a direct lateral approach with a rectangular stem. Eighty-two patients ≥80 years of age underwent THA due to a displaced femoral neck. Clinical frailty scale (CFS) scores <5 were indicated for THA. The modified Harris hip score (mHHS), visual analogue scale (VAS), and patient satisfaction were used to assess outcomes. RESULTS: Nine of 82 patients died in the study period with another underlying disease. One, a 90-year-old male with pneumonia expired in the intensive care unit at 7-day postoperatively, while the other eight died due to causes unrelated to THA. Of the remaining 73 patients: (i) mean mHHS score increased to 80.57±21.36 at 1-year postoperatively; (ii) VAS was 2.3±0.9 points six-months postoperatively; and (iii) 78.7% of patients reported that they were very satisfied or satisfied 1-year postoperatively. The number of perioperative complications was 10.8% (9 hips) without the need for revision surgery. CONCLUSION: The use of THA in patients ≥80 years of age with low CFS scores (<5) described here yielded favorable results and a relatively low rate of complications. However, a well-controlled comparative study or randomized trial is required to further refine selection criteria for THA in this patient population.

Acute compartment syndrome of the forearm associated with transradial coronary intervention.

This study documents our experience with acute forearm compartment syndrome after percutaneous transradial coronary artery intervention and suggests several strategies to achieve good results. A retrospective review identified the medical records of four patients with acute forearm compartment syndrome after transradial intervention who were treated by urgent fasciotomy. The mean time from the onset of symptoms to operation was 5.7 hours. In three cases bleeding was from radial artery rupture at the puncture site, and one case was caused by brachial artery rupture at the level of the distal humerus and radial artery rupture at the level of proximal forearm. We obtained satisfactory results without any complications. If acute forearm compartment syndrome after transradial intervention is diagnosed, the site of bleeding should be identified preoperatively. Early surgical decompression produced satisfactory results even in elderly patients.Level of evidence: IV.

Stabilized Loading of Hyaluronic Acid-Containing Hydrogels into Magnesium-Based Cannulated Screws.

Cannulated screws have a structure for inserting a guide wire inside them to effectively correct complicated fractures. Magnesium, an absorbable metal used to manufacture cannulated screws, may decompose in the body after a certain period of implantation. The hydrogel formed by hyaluronic acid (HA) and polygalacturonic acid (PGA) has been used into Mg-based cannulated screws to prevent bone resorption owing to the rapid corrosion of Mg with unfavorable mechanical properties and a high ambient pH. In addition, Ca ions were added to the gel for cross-linking the carboxyl groups to modify the gelation rate and physical properties of the gel. The developed hydrogels were injected into the Mg-based cannulated screws, after which they released HA and Ca. The possibility of the application of this system as a cannulated screw was evaluated based on the corrosion resistance, gel degradation rate, HA release, toxicity toward osteocytes, and experiments involving the implantation of the screws into the femurs of rats. Ca ions first bound to PGA and delayed the gelation time and dissolution rate. However, they interfered with HA binding and increased the elution of HA at the beginning of gel degradation. Ca(NO3)2 concentrations higher than 0.01 M and low pH environments inhibited osteoblast differentiation and proliferation, owing to the elution of HA from the hydrogel. On the other hand, when the HA hydrogel with a proper amount of Ca was inserted into a magnesium screw, the degradation of Mg was delayed, and the presence of the gel contributed to new bone formation and osteocyte expansion.

Decellularized extracellular matrix bioinks and the external stimuli to enhance cardiac tissue development in vitro.

Engineered heart tissue (EHT) has ample potential as a model for in vitro tissue modeling or tissue regeneration. Using 3D cell printing technology, various hydrogels have been utilized as bioinks to fabricate EHT to date. However, its efficacy has remained limited due to poor functional properties of the cultured cardiomyocytes stemming from a lack of proper microenvironmental cues. Specifically, the surrounding matrix plays a key role in modulating cardiomyocyte differentiation and maturation. Recently, the use of heart tissue-derived extracellular matrix (hdECM) bioink has come to be seen as one of the most promising candidates due to its functional and structural similarities to native tissue. Here, we demonstrated a correlation between the synthesis of cardiomyocyte-specific proteins and the surrounding microenvironment irrespective of the similar material chemistry. Primary cardiomyocytes isolated from neonatal rats were encapsulated in different composition and concentration of bioinks (hdECM and collagen). The bioinks were sequentially printed using an extrusion-based 3D bioprinter and cultured either statically or dynamically. Qualitative and quantitative evaluation revealed enhanced maturation of cardiomyocytes in hdECM, unlike the collagen group under similar culture conditions. Specifically, 3D-printed EHT using a low concentration of hdECM promoted early differentiation of cardiomyocytes. Hence, the present study provides experimental insights regarding the establishment of a 3D-printed cardiac tissue model, highlighting that the matrix and the culture microenvironment can be decisive factors for cell-material interactions that affect cardiomyocyte maturation. STATEMENT OF SIGNIFICANCE: The regulation of signal transduction and responses to extracellular matrices (ECMs) is of particular relevance in tissue maturation. In particular, there is a clear need to understand the structural and phenotypical modulation in cardiomyocytes with respect to the surrounding microenvironment. Exploration of the key regulators, such as the compositional and the biophysical properties of bioinks associated directly with cell-cell and cell-matrix interactions would assist with the fabrication of cardiac tissue constructs with enhanced functionality. Hence, we documented the synergistic effects of surrounding matrices and culture conditions on the maturation of cardiomyocytes. Additionally, we highlighted the potential of using 3D bioprinting techniques to fabricate uniformly aligned cardiac constructs for mid- to high-throughput drug testing platforms that have great reproducibility and versatility.

Evaluation of mechanical strength and bone regeneration ability of 3D printed kagome-structure scaffold using rabbit calvarial defect model.

In clinical conditions, the reconstructions performed in the complex and three-dimensional bone defects in the craniomaxillofacial (CMF) area are often limited in facial esthetics and jaw function. Furthermore, to regenerate a bone defect in the CMF area, the used scaffold should have unique features such as different mechanical strength or physical property suitable for complex shape and function of the CMF bones. Therefore, a three-dimensional synthetic scaffold with a patient-customized structure and mechanical properties is more suitable for the regeneration. In this study, the customized kagome-structure scaffold with complex morphology was assessed in vivo. The customized 3D kagome-structure model for the defect region was designed according to data using 3D computed tomography. The kagome-structure scaffold and the conventional grid-structure scaffold (as a control group) were fabricated using a 3D printer with a precision extruding deposition head using poly(ε-caprolactone) (PCL). The two types of 3D printed scaffolds were implanted in the 8-shaped defect model on the rabbit calvarium. To evaluate the osteoconductivity of the implanted scaffolds, new bone formation, hematoxylin and eosin staining, immunohistochemistry, and Masson's trichrome staining were evaluated for 16 weeks after implantation of the scaffolds. To assess the mechanical robustness and stability of the kagome-structure scaffold, numerical analysis considering the 'elastic-perfectly plastic' material properties and deformation under self-contact condition was performed by finite element analysis. As a result, the kagome-structure scaffold fabricated using 3D printing technology showed excellent mechanical robustness and enhanced osteoconductivity than the control group. Therefore, the 3D printed kagome-structure scaffold can be a better option for bone regeneration in complex and large defects than the conventional grid-type 3D printed scaffold.

Accelerated Bone Regeneration via Three-Dimensional Cell-Printed Constructs Containing Human Nasal Turbinate-Derived Stem Cells as a Clinically Applicable Therapy.

Stem cell transplantation is a promising therapeutic strategy that includes both cell therapy and tissue engineering for the treatment of many regenerative diseases; however, the efficacy and safety of stem cell therapy depend on the cell type used in therapeutic and translational applications. In this study, we validated the hypothesis that human nasal turbinate-derived mesenchymal stem cells (hTMSCs) are a potential therapeutic source of adult stem cells for clinical use in bone tissue engineering using three-dimensional (3D) cell-printing technology. hTMSCs were cultured and evaluated for clinical use according to their cell growth, cell size, and preclinical safety and were then incorporated into a multicompositional 3D bioprinting system and investigated for bone tissue regeneration in vitro and in vivo. Finally, hTMSCs were compared with human bone marrow-derived MSCs (hBMSCs), which are the most common stem cell type used in regenerative medicine. hTMSCs from three different donors showed greater and faster cell growth than hBMSCs from two different donors when cultured. The hTMSCs were smaller in size than the hBMSCs. Furthermore, the hTMSCs did not exhibit safety issues in immunodeficient mice. hTMSCs in 3D-printed constructs (3D-hTMSC) showed much greater viability, growth, and osteogenic differentiation potential in vitro than hBMSCs in 3D-printed constructs (3D-hBMSC). Likewise, 3D-hTMSC showed better cell survival and alkaline phosphatase activity and greater osteogenic protein expression than 3D-hBMSC upon subcutaneous implantation into the dorsal region of nude mice. Notably, in an orthotopic model involving implantation into a tibial defect in rats, implantation of 3D-hTMSC led to greater bone matrix formation and enhanced bone healing to a greater degree than implantation of 3D-hBMSC. The clinically reliable evidence provided by these results is underlined by the potential for rapid tissue regeneration and ambulation in bone fracture patients implanted with 3D-hTMSC.

Rabbit Calvarial Defect Model for Customized 3D-Printed Bone Grafts.

Bone graft materials are commonly used to regenerate various bone defects, but their application is often limited because of the complex defect shape in various clinical conditions. Hence, customized bone grafts using three-dimensional (3D) printing techniques have been developed. However, conventional simple bone defect models are limited for evaluating the benefits and manufacturing accuracy of 3D-printed customized bone grafts. Thus, the aim of the present study was to develop a complex-shaped bone defect model. We designed an 8-shaped bony defect that consists of two simple circles attached to the rabbit calvarium. To determine the critical-sized defect (CSD) of the 8-shaped defects, 5.6- and 7-mm-diameter trephine burs were tested, and the 7-mm-diameter bur could successfully create a CSD, which was easily reproducible on the rabbit calvarium. The rate of new bone formation was 28.65% ± 8.63% at 16 weeks following creation of the defect. To confirm its efficacy for clinical use, the 8-shaped defect was created on a rabbit calvarium and 3D computed tomography (CT) was performed. A stereolithography file was produced using the CT data, and a 3D-printed polycaprolactone graft was fabricated. Using our 8-shaped defect model, we were able to modify the tolerances of the bone graft and calvarial defect to fabricate a more precise bone graft. Customized characteristics of the bone graft were then used to improve the accuracy of the bone graft. In addition, we confirmed the fitting ability of the 3D-printed graft during implantation of the graft. Our 8-shaped defect model on the rabbit calvarium using a 7.0-mm trephine bur may be a useful CSD model for evaluating 3D-printed graft materials.

Fabrication of Microchannels and Evaluation of Guided Vascularization in Biomimetic Hydrogels.

BACKGROUND: The fabrication of microchannels in hydrogel can facilitate the perfusion of nutrients and oxygen, which leads to guidance cues for vasculogenesis. Microchannel patterning in biomimetic hydrogels is a challenging issue for tissue regeneration because of the inherent low formability of hydrogels in a complex configuration. We fabricated microchannels using wire network molding and immobilized the angiogenic factors in the hydrogel and evaluated the vasculogenesis in vitro and in vivo. METHODS: Microchannels were fabricated in a hyaluronic acid-based biomimetic hydrogel by using "wire network molding" technology. Substance P was immobilized in acrylated hyaluronic acid for angiogenic cues using Michael type addition reaction. In vitro and in vivo angiogenic activities of hydrogel with microchannels were evaluated. RESULTS: In vitro cell culture experiment shows that cell viability in two experimental biomimetic hydrogels (with microchannels and microchannels + SP) was higher than that of a biomimetic hydrogel without microchannels (bulk group). Evaluation on differentiation of human mesenchymal stem cells (hMSCs) in biomimetic hydrogels with fabricated microchannels shows that the differentiation of hMSC into endothelial cells was significantly increased compared with that of the bulk group. In vivo angiogenesis analysis shows that thin blood vessels of approximately 25-30 µm in diameter were observed in the microchannel group and microchannel + SP group, whereas not seen in the bulk group. CONCLUSION: The strategy of fabricating microchannels in a biomimetic hydrogel and simultaneously providing a chemical cue for angiogenesis is a promising formula for large-scale tissue regeneration.

Development and Evaluation of Hyaluronic Acid-Based Hybrid Bio-Ink for Tissue Regeneration.

BACKGROUND: Bioprinting has recently appeared as a powerful tool for building complex tissue and organ structures. However, the application of bioprinting to regenerative medicine has limitations, due to the restricted choices of bio-ink for cytocompatible cell encapsulation and the integrity of the fabricated structures. METHODS: In this study, we developed hybrid bio-inks based on acrylated hyaluronic acid (HA) for immobilizing bio-active peptides and tyramine-conjugated hyaluronic acids for fast gelation. RESULTS: Conventional acrylated HA-based hydrogels have a gelation time of more than 30 min, whereas hybrid bio-ink has been rapidly gelated within 200 s. Fibroblast cells cultured in this hybrid bio-ink up to 7 days showed > 90% viability. As a guidance cue for stem cell differentiation, we immobilized four different bio-active peptides: BMP-7-derived peptides (BMP-7D) and osteopontin for osteogenesis, and substance-P (SP) and Ac-SDKP (SDKP) for angiogenesis. Mesenchymal stem cells cultured in these hybrid bio-inks showed the highest angiogenic and osteogenic activity cultured in bio-ink immobilized with a SP or BMP-7D peptide. This bio-ink was loaded in a three-dimensional (3D) bioprinting device showing reproducible printing features. CONCLUSION: We have developed bio-inks that combine biochemical and mechanical cues. Biochemical cues were able to regulate differentiation of cells, and mechanical cues enabled printing structuring. This multi-functional bio-ink can be used for complex tissue engineering and regenerative medicine.

Assessments for bone regeneration using the polycaprolactone SLUP (salt-leaching using powder) scaffold.

Salt-leaching using powder (SLUP) scaffolds are novel salt-leaching scaffolds with well-interconnected pores that do not require an organic solvent or high pressure. In this study, in vitro and in vivo cell behaviors were assessed using a PCL (polycaprolactone) SLUP scaffold. Moreover, using PCL, conventional salt-leaching and 3D-plotted scaffolds were fabricated as control scaffolds. Morphology, mechanical property, water absorption, and in vitro/in vivo cell response assessments were performed to clarify the characteristics of the SLUP scaffold compared with control scaffolds. Consequently, we verified that the interconnectivity between the pores of the SLUP scaffold was enhanced compared with conventional salt-leaching scaffolds. Moreover, in vitro cell attachment and proliferation of the SLUP scaffold were higher than those of the 3D-plotted scaffold because of their morphological characteristic. Furthermore, we revealed that new bone formation and bone ingrowth of the SLUP scaffold was superior to those of the calvarial defect model and 3D-plotted scaffold because of the high porosity and improved interconnectivity of pores by the SLUP technique without high pressure using powders. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3432-3444, 2017.

Mechanical properties and cell-culture characteristics of a polycaprolactone kagome-structure scaffold fabricated by a precision extruding deposition system.

To enhance the mechanical properties of three-dimensional (3D) scaffolds used for bone regeneration in tissue engineering, many researchers have studied their structure and chemistry. In the structural engineering field, the kagome structure has been known to have an excellent relative strength. In this study, to enhance the mechanical properties of a synthetic polymer scaffold used for tissue engineering, we applied the 3D kagome structure to a porous scaffold for bone regeneration. Prior to fabricating the biocompatible-polymer scaffold, the ideal kagome structure, which was manufactured by a 3D printer of the digital light processing type, was compared with a grid-structure, which was used as the control group, using a compressive experiment. A polycaprolactone (PCL) kagome-structure scaffold was successfully fabricated by additive manufacturing using a 3D printer with a precision extruding deposition head. To assess the physical characteristics of the fabricated PCL-kagome-structure scaffold, we analyzed its porosity, pore size, morphological structure, surface roughness, compressive stiffness, and mechanical bending properties. The results showed that, the mechanical properties of proposed kagome-structure scaffold were superior to those of a grid-structure scaffold. Moreover, Sarcoma osteogenic (Saos-2) cells were used to evaluate the characteristics of in vitro cell proliferation. We carried out cell counting kit-8 (CCK-8) and DNA contents assays. Consequently, the cell proliferation of the kagome-structure scaffold was increased; this could be because the surface roughness of the kagome-structure scaffold enhances initial cell attachment.

Improvement of mechanical strength and osteogenic potential of calcium sulfate-based hydroxyapatite 3-dimensional printed scaffolds by ε-polycarbonate coating.

Powder-based three-dimensional (3D) printing is an excellent method to fabricate complex-shaped scaffolds for tissue engineering. However, their lower mechanical strength restricts their application in bone tissue engineering. Here, we created a 3D-printed scaffold coated with a ε-polycaprolactone (PCL) polymer solution (5 and 10 w/v %) to improve the mechanical strength of the scaffold. The 3D scaffold was fabricated from calcium sulfate hemihydrate powder (CaSO4-1/2 H2O), transformed into hydroxyapatite (HAp) by treatment with a hydrothermal reaction in an NH4H2PO4 solution. The surface properties and composition of the scaffold were evaluated using scanning electron microscopy and X-ray diffraction analysis. We demonstrated that the 3D scaffold coated with PCL had an improved mechanical modulus. Coating with 5 and 10% PCL increased the compressive strength significantly, by about 2-fold and 4-fold, respectively, compared with that of uncoated scaffolds. However, the porosity was reduced significantly by coating with 10% PCL. In vitro biological evaluation demonstrated that MG-63 cells adhered well and proliferated on the 3D scaffold coated with PCL, and the scaffold was not cytotoxic. In addition, alkaline phosphatase activity and real time polymerase chain reaction demonstrated that osteoblast differentiation also improved in the PCL-coated 3D scaffolds. These results indicated that PCL polymer coating could improve the compressive strength and biocompatibility of 3D HAp scaffolds for bone tissue engineering applications.

Novel Function of Lysine Methyltransferase G9a in the Regulation of Sox2 Protein Stability.

G9a is a lysine methyltransferase (KMTase) for histone H3 lysine 9 that plays critical roles in a number of biological processes. Emerging evidence suggests that aberrant expression of G9a contributes to tumor metastasis and maintenance of a malignant phenotype in cancer by inducing epigenetic silencing of tumor suppressor genes. Here, we show that G9a regulates Sox2 protein stability in breast cancer cells. When G9a lysine methyltransferase activity was chemically inhibited in the ER(+) breast cancer cell line MCF7, Sox2 protein levels were decreased. In addition, ectopic overexpression of G9a induced accumulation of Sox2. Changes in cell migration, invasion, and mammosphere formation by MCF7 cells were correlated with the activity or expression level of G9a. Ectopic expression of G9a also increased Sox2 protein levels in another ER(+) breast cancer cell line, ZR-75-1, whereas it did not affect Sox2 expression in MDA-MB-231 cells, an ER(-) breast cancer cell line, or in glioblastoma cell lines. Furthermore, treatment of mouse embryonic stem cells with a KMT inhibitor, BIX-01294, resulted in a rapid reduction in Sox2 protein expression despite increased Sox2 transcript levels. This finding suggests that G9a has a novel function in the regulation of Sox2 protein stability in a cell type-dependent manner.

Predictability of preoperative 18F-FDG PET for histopathological differentiation and early recurrence of primary malignant intrahepatic tumors.

OBJECTIVE: The limited studies with 18F-fluorodeoxyglucose (18F-FDG)-PET reported results and interpretations that differed between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC). We investigated the correlation between preoperative PET results and postoperative prognosis, including early (time-to-recurrence<6 months) tumor recurrence, and histopathological tumor differentiation in patients who had undergone surgery for primary malignant intrahepatic tumors, including HCC and IHCC. MATERIALS AND METHODS: We retrospectively reviewed 357 patients who had undergone curative surgery for malignant hepatic tumors, including primary HCC or IHCC, other than Klatskin tumors at a tertiary academic hospital between January 2005 and June 2012. All patients had undergone an 18F-FDG PET/computed tomography scan preoperatively and the maximum standardized uptake value of the tumor (max SUV tumor) and the tumor-to-nontumor SUV ratio (TNR) were calculated from 18F-FDG uptake. Histopathological differentiation grading was confirmed postoperatively. RESULTS: Among the patients, 115 cases with primary malignant intrahepatic tumors fulfilled the inclusion criteria. On univariate analysis, preoperative max SUV tumor and TNR showed a correlation with the overall and early tumor recurrence of HCC, but only max SUV tumor was associated with overall and early recurrence of IHCC (P<0.05). When considering postoperative histopathological differentiation, a correlation between max SUV tumor and TNR with HCC and between max SUV tumor and IHCC was found (P<0.05). However, on multivariate analysis, only early recurrence was associated with TNR in HCC and with max SUV tumor in IHCC. CONCLUSION: A preoperative 18F-FDG PET scan can be considered a useful reference for postoperative tumor recurrence and histopathological differentiation in cases of primary malignant intrahepatic tumors. 18F-FDG PET scan results should be interpreted separately for malignant liver tumors.

Treatment of lamivudine-resistant chronic hepatitis B infection: a multicenter retrospective study.

OBJECTIVES: To compare the efficacy of rescue therapies in lamivudine (LAM)-resistant chronic hepatitis B (CHB) infections including: (1) adefovir dipivoxil (ADV) monotherapy, (2) ADV plus LAM combination therapy and (3) entecavir (ETV) 1.0 mg monotherapy. MATERIALS AND METHODS: The authors designed a multicenter-retrospective study. Eight institutions participated in the study from Korea. RESULTS: A total of 343 LAM-resistant CHB patients were enrolled. The proportion of patients with undetectable serum hepatitis B virus (HBV) DNA levels at month 24 after the initiation of rescue therapy was higher in the ADV plus LAM combination therapy group (39/64, 60.9%) than in the ADV monotherapy (50/126, 39.7%) and ETV 1.0 mg monotherapy (19/48, 39.6%) groups (p = 0.014). Mean serum HBV DNA levels at 24 months were 2.07 ± 1.21 log(10) IU/ml in the ADV plus LAM combination therapy group, 2.74 ± 1.74 log(10) IU/ml in the ADV monotherapy group and 3.08 ± 1.97 log(10) IU/ml in the ETV 1.0 mg monotherapy group (p = 0.014). In multivariate analysis, a finding of undetectable serum HBV DNA level at 6 months and ADV plus LAM combination therapy (vs. ADV) was an independent factor for predicting undetectable serum HBV DNA at month 24 (odds ratio, 1.003; 95% confidence interval, 1.000-1.006; p = 0.026). CONCLUSIONS: ADV plus LAM combination therapy is more effective in reducing viral load than switching to ADV or ETV 1.0 mg in patients with LAM-resistant CHB.