Regeneration of Volumetric Muscle Loss Using MSCs Encapsulated in PRP-Derived Fibrin Microbeads.

Volumetric muscle loss (VML) is one of the major types of soft tissue injury frequently encountered worldwide. In case of VML, the endogenous regenerative capacity of the skeletal muscle tissue is usually not sufficient for complete healing of the damaged area resulting in permanent functional musculoskeletal impairment. Therefore, the development of new tissue engineering approaches that will enable functional skeletal muscle regeneration by overcoming the limitations of current clinical treatments for VML injuries has become a critical goal. Platelet-rich plasma (PRP) is an inexpensive and relatively effective blood product with a high concentration of platelets containing various growth factors and cytokines involved in wound healing and tissue regeneration. Due to its autologous nature, PRP has been a safe and widely used treatment option for various wound types for many years. Recently, PRP-based biomaterials have emerged as a promising approach to promote muscle tissue regeneration upon injury. This chapter describes the use of PRP-derived fibrin microbeads as a versatile encapsulation matrix for the localized delivery of mesenchymal stem cells and growth factors to treat VML using tissue engineering strategies.

Magnetic biocomposite scaffold based on decellularized tendon ECM and MNP-deposited halloysite nanotubes: physicochemical, thermal, rheological, mechanical andin vitrobiological evaluations.

The development of new three-dimensional biomaterials with advanced versatile properties is critical to the success of tissue engineering (TE) applications. Here, (a) bioactive decellularized tendon extracellular matrix (dECM) with a sol-gel transition feature at physiological temperature, (b) halloysite nanotubes (HNT) with known mechanical properties and bioactivity, and (c) magnetic nanoparticles (MNP) with superparamagnetic and osteogenic properties were combined to develop a new scaffold that could be used in prospective bone TE applications. Deposition of MNPs on HNTs resulted in magnetic nanostructures without agglomeration of MNPs. A completely cell-free, collagen- and glycosaminoglycan- rich dECM was obtained and characterized. dECM-based scaffolds incorporated with 1%, 2% and 4% MNP-HNT were analysed for their physical, chemical, andin vitrobiological properties. Fourier-transform infrared spectroscopy, x-ray powder diffractometry and vibrating sample magnetometry analyses confirmed the presence of dECM, HNT and MNP in all scaffold types. The capacity to form apatite layer upon incubation in simulated body fluid revealed that dECM-MNP-HNT is a bioactive material. Combining dECM with MNP-HNT improved the thermal stability and compressive strength of the macroporous scaffolds upto 2% MNP-HNT.In vitrocytotoxicity and hemolysis experiments showed that the scaffolds were essentially biocompatible. Human bone marrow mesenchymal stem cells adhered and proliferated well on the macroporous constructs containing 1% and 2% MNP-HNT; and remained metabolically active for at least 21 din vitro. Collectively, the findings support the idea that magnetic nanocomposite dECM scaffolds containing MNP-HNT could be a potential template for TE applications.

Biomimetic mineralization of platelet lysate/oxidized dextran cryogel as a macroporous 3D composite scaffold for bone repair.

Scaffold development approaches using autologous sources for tissue repair are of great importance in obtaining bio-active/-compatible constructs. Platelet-rich plasma (PRP) containing various growth factors and platelet lysate (PL) derived from PRP are autologous products that have the potential to accelerate the tissue repair response by inducing a transient inflammatory event. Considering the regenerative capacity of PRP and PL, PRP/PL-based scaffolds are thought to hold great promise for tissue engineering as a natural source of autologous growth factors and a provider of mechanical support for cells. Here, a bio-mineralized PRP-based scaffold was developed using oxidized dextran (OD) and evaluated for future application in bone tissue engineering. Prepared PL/OD scaffolds were incubated in simulated body fluid (SBF) for 7, 14 and 21 d periods. Mineralized PL/OD scaffolds were characterized using Fourier transform infrared spectroscopy, x-ray diffraction spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis, porosity and compression tests. SEM and energy-dispersive x-ray spectroscopy analyses revealed mineral accumulation on the PL/OD scaffold as a result of SBF incubation.In vitrocytotoxicity andin vitrohemolysis tests revealed that the scaffolds were non-toxic and hemocompatible. Additionally, human osteoblasts (hOBs) exhibited good attachment and spreading behavior on the scaffolds and maintained their viability throughout the culture period. The alkaline phosphatase activity assay and calcium release results revealed that PL/OD scaffolds preserved the osteogenic properties of hOBs. Overall, findings suggest that mineralized PL/OD scaffold may be a promising scaffold for bone tissue engineering.

Decellularized Bone Matrix/45S5 Bioactive Glass Biocomposite Hydrogel-Based Constructs with Angiogenic and Osteogenic Properties: Ex Ovo and Ex Vivo Evaluations.

Decellularized extracellular matrix is often used to create an in vivo-like environment that supports cell growth and proliferation, as it reflects the micro/macrostructure and molecular composition of tissues. On the other hand, bioactive glasses (BG) are surface-reactive glass-ceramics that can convert to hydroxyapatite in vivo and promote new bone formation. This study is designed to evaluate the key properties of a novel angiogenic and osteogenic biocomposite graft made of bovine decellularized bone matrix (DBM) hydrogel and 45S5 BG microparticles (10 and 20 wt%) to combine the existing superior properties of both biomaterial classes. Morphological, physicochemical, mechanical, and thermal characterizations of DBM and DBM/BG composite hydrogels are performed. Their in vitro biocompatibility is confirmed by cytotoxicity and hemocompatibility analyses. Ex vivo chick embryo aortic arch and ex ovo chick chorioallantoic membrane (CAM) assays reveal that the present pro-angiogenic property of DBM hydrogels is enhanced by the incorporation of BG. Histochemical stainings (Alcian blue and Alizarin red) and digital image analysis of ossification on hind limbs of embryos used in the CAM model reveal the osteogenic potential of biomaterials. The findings support the notion that the developed DBM/BG composite hydrogel constructs have the potential to be a suitable graft for bone repair.

Advanced liposome and polymersome-based drug delivery systems: Considerations for physicochemical properties, targeting strategies and stimuli-sensitive approaches.

Liposomes and polymersomes are colloidal vesicles that are self-assembled from lipids and amphiphilic polymers, respectively. Because of their ability to encapsulate both hydrophilic and hydrophobic therapeutics, they are of great interest in drug delivery research. Today, the applications of liposomes and polymersomes have expanded to a wide variety of complex therapeutic molecules, including nucleic acids, proteins and enzymes. Thanks to their chemical versatility, they can be tailored to different drug delivery applications to achieve maximum therapeutic index. This review article evaluates liposomes and polymersomes from a perspective that takes into account the physical and biological barriers that reduce the efficiency of the drug delivery process. In this context, the design approaches of liposomes and polymersomes are discussed with representative examples in terms of their physicochemical properties (size, shape, charge, mechanical), targeting strategies (passive and active) and response to different stimuli (pH, redox, enzyme, temperature, light, magnetic field, ultrasound). Finally, the challenges limiting the transition from laboratory to practice, recent clinical developments, and future perspectives are addressed.

The relationship between executive functions and chronotype in healthy siblings of children with autism spectrum disorder.

The aim of this study is to examine executive functions in healthy siblings of children with autism spectrum disorder (ASD) and to evaluate the relationship between chronotype and executive functions (EF). This study included 40 healthy siblings (case group) of children with ASD and 40 healthy controls. Executive functions were evaluated by Stroop Test, Serial Digit Learning Test (SDLT) and Cancellation Test (CT). Children's Chronotype Questionnaire (CCTQ) and Autism Spectrum Screening Questionnaire (ASSQ) were administered to parents. It was determined that the Stroop Test and CT performances of the case group were significantly worse than the control group. There was no difference in SDLT. It was determined that the total CCTQ score of the case group was significantly higher. In addition, a significant positive correlation was found between the chronotype total score and the number of false targets in the second part of CT. In the logistic regression analysis; the chronotype total score, Stroop test fifth part correction number and CT fourth part error number were determined as possible factors in the differentiation of the case and control groups. More studies are needed to evaluate the relationship between executive functions and chronotype in siblings of children with ASD.

Advances in Regenerative Medicine and Biomaterials.

The low regenerative potential of the human body hinders proper regeneration of dysfunctional or lost tissues and organs due to trauma, congenital defects, and diseases. Tissue or organ transplantation has hence been a major conventional option for replacing the diseased or dysfunctional body parts of the patients. In fact, a great number of patients on waiting lists would benefit tremendously if tissue and organs could be replaced with biomimetic spare parts on demand. Herein, regenerative medicine and advanced biomaterials strive to reach this distant goal. Tissue engineering aims to create new biological tissue or organ substitutes, and promote regeneration of damaged or diseased tissue and organs. This approach has been jointly evolving with the major advances in biomaterials, stem cells, and additive manufacturing technologies. In particular, three-dimensional (3D) bioprinting utilizes 3D printing to fabricate viable tissue-like structures (perhaps organs in the future) using bioinks composed of special hydrogels, cells, growth factors, and other bioactive contents. A third generation of multifunctional biomaterials could also show opportunities for building biomimetic scaffolds, upon which to regenerate stem cells in vivo. Besides, decellularization technology based on isolation of extracellular matrix of tissue and organs from their inhabiting cells is presented as an alternative to synthetic biomaterials. Today, the gained knowledge of functional microtissue engineering and biointerfaces, along with the remarkable advances in pluripotent stem cell technology, seems to be instrumental for the development of more realistic microphysiological 3D in vitro tissue models, which can be utilized for personalized disease modeling and drug development. This chapter will discuss the recent advances in the field of regenerative medicine and biomaterials, alongside challenges, limitations, and potentials of the current technologies.

Bioactive composite hydrogels as 3D mesenchymal stem cell encapsulation environment for bone tissue engineering: in vitro and in vivo studies.

Although decellularized bone matrix (DBM) has often been used in scaffold form for osteogenic applications, its use as a stem cell encapsulation matrix adaptable to surgical shaping procedures has been neglected. This study aimed to investigate the feasibility of utilizing solubilized DBM and nanohydroxyapatite (nHAp)-incorporated DBM hydrogels as encapsulation matrix for bone marrow-derived MSCs (BM-MSCs). First, DBM and DBM/nHAp hydrogels were assessed by physical, chemical, turbidimetric, thermal, and mechanical methods; then, in vitro cytocompatibility and in vitro hemocompatibility were investigated. An in vivo study was performed to evaluate the osteogenic properties of hydrogels alone or with BM-MSCs encapsulated in them. The findings revealed that hydrogels retained high levels of collagen and glycosaminoglycans after successful decellularization. They were found to be cytocompatible and hemocompatible in vitro, and were able to gel with sufficient mechanical stability at physiological temperature. BM-MSCs survived in culture for at least 2 weeks as metabolically active when encapsulated in both DBM and DBM/nHAp. Preliminary in vivo study showed that DBM-nHAp has higher osteogenicity than DBM. Moreover, BM-MSC encapsulated DMB/nHAp showed predominant bone-like tissue formation at 30 days in the rat ectopic site compared to its cell-free form.

Comparison of Limberg Flap and Karydakis Flap Repair in Pilonidal Sinus Surgery: A Prospective Case-Control Study.

Background Pilonidal sinus disease (PSD) is a chronic inflammation and infection of the sacrococcygeal region. It often affects young adult males and produces clinical findings with abscess and discharge in the sacrococcygeal region or painful sinus tract in the natal cleft. The best surgical technique for sacrococcygeal PSD is still disputed. This study aimed to compare the Karydakis flap technique (KFT) and Limberg flap technique (LFT) used in the surgical treatment of the sacrococcygeal pilonidal sinus. Methodology A total of 140 patients diagnosed with pilonidal sinus between 2010 and 2012 were included in the study. The patients were divided into two groups, namely, LFT (n = 73) and KFT (n = 67). Preoperative findings of the patients, surgical findings, and short and long-term postoperative findings were recorded and statistically compared. Results Regarding cosmetic results, the Karydakis flap was better than the Limberg flap with a faster return to normal life. There was no statistical difference between the two groups concerning wound dehiscence, postoperative visual analog scale scores, seroma formation, and recurrence. Conclusions Considering the faster return to normal life and greater cosmetic satisfaction of the patients, the KFT should be chosen instead of the LFT as the standard technique in pilonidal sinus surgery.

Evaluation of Human Osteoblasts on NIPS Micro-Patterned PCL Carriers Containing Nanohydroxyapatite and Reduced Graphene Oxide Using PSµM.

The content and surface topology of tissue engineering scaffolds are two important parameters in regulating the cell behavior. In this study, a phase separation micromolding (PSµM) method was implemented to develop micro-groove-imprinted poly(ε-caprolactone) (PCL)-nano hydroxyapatite (nHAp)-reduced graphene oxide (rGO) ternary blend constructs. Physical and chemical characterizations of cell-devoid constructs were performed by FTIR, XRD, TGA, DSC, porosity, swelling, wettability analysis, tensile and compression mechanical tests. The in vitro biological performance of human osteoblasts cultured on micro-patterned blend constructs was evaluated by MTT and alamarBlue viability assays. The findings revealed that nHAp and rGO significantly promote cell viability and proliferation, while the micro-pattern determines the direction of cell migration. Alkaline phosphatase and Ca2+ analyses were carried out to determine the osteogenic properties of cell-laden constructs. This study describes a simple method to generate topologically modified ternary blend PCL/nHAp/rGO constructs using the PSµM method, which contributes to cell proliferation and migration, which is particularly important in regenerative medicine.

Rectus sheath hematoma as a revisited and rare cause of abdominal pain?

OBJECTIVES: Rectus sheath hematoma is the accumulation of blood within rectus abdominis muscle. The aim of this study was to investigate the clinical presentation, diagnostic methods, treatment strategy, and outcomes of patients diagnosed with rectus sheath hematoma. METHODS: Patients diagnosed and treated for spontaneous rectus sheath hematoma between January 2014 and December 2019 were included in the study. RESULTS: A total of 11 patients were diagnosed as spontaneous rectus sheath hematoma, with a median age of 63.5 ± IQR (55.5-73.25). 8 patients were treated by transfusion and medical therapy, while two patients underwent surgery and drainage. One patient was treated with arterial embolization. No mortality was encountered. CONCLUSION: Anticoagulant therapy was a major risk factor. Treatment is mostly based on supportive care to maintain hemodynamic stability. KEY WORDS: Abdominal pain, Hematoma, Interventional radiology, Rectus sheath.

Development of a multicellular 3D-bioprinted microtissue model of human periodontal ligament-alveolar bone biointerface: Towards a pre-clinical model of periodontal diseases and personalized periodontal tissue engineering.

While periodontal (PD) disease is among principal causes of tooth loss worldwide, regulation of concomitant soft and mineralized PD tissues, and PD pathogenesis have not been completely clarified yet. Besides, relevant pre-clinical models and in vitro platforms have limitations in simulating human physiology. Here, we have harnessed three-dimensional bioprinting (3DBP) technology for developing a multi-cellular microtissue model resembling PD ligament-alveolar bone (PDL-AB) biointerface for the first time. 3DBP parameters were optimized; the physical, chemical, rheological, mechanical, and thermal properties of the constructs were assessed. Constructs containing gelatin methacryloyl (Gel-MA) and hydroxyapatite-magnetic iron oxide nanoparticles showed higher level of compressive strength when compared with that of Gel-MA constructs. Bioprinted self-supporting microtissue was cultured under flow in a microfluidic platform for >10 days without significant loss of shape fidelity. Confocal microscopy analysis indicated that encapsulated cells were homogenously distributed inside the matrix and preserved their viability for >7 days under microfluidic conditions. Immunofluorescence analysis showed the cohesion of stromal cell surface marker-1+ human PDL fibroblasts containing PDL layer with the osteocalcin+ human osteoblasts containing mineralized layer in time, demonstrating some permeability of the printed constructs to cell migration. Preliminary tetracycline interaction study indicated the uptake of model drug by the cells inside the 3D-microtissue. Also, the non-toxic levels of tetracycline were determined for the encapsulated cells. Thus, the effects of tetracyclines on PDL-AB have clinical significance for treating PD diseases. This 3D-bioprinted multi-cellular periodontal/osteoblastic microtissue model has potential as an in vitro platform for studying processes of the human PDL.

Macro- and microporous polycaprolactone/duck's feet collagen scaffold fabricated by combining facile phase separation and particulate leaching techniques to enhance osteogenesis for bone tissue engineering.

Herein, a facile macro- and microporous polycaprolactone/duck's feet collagen scaffold (PCL/DC) was fabricated and characterized to confirm its applicability in bone tissue engineering. A biomimetic scaffold for bone tissue engineering and regeneration for bone defects is an important element. PCL is a widely applied biomaterial for bone tissue engineering due to its biocompatibility and biodegradability. However, the high hydrophobicity and low cell attachment site properties of PCL lead to an insufficient microenvironment in designing a scaffold. Collagen is a nature-derived biomaterial that is widely used in tissue engineering and has excellent biocompatibility, mechanical properties, and cell attachment moieties. Among the resources from which collagen can be obtained, DC contains a high amount of collagen type I (COL1), is biocompatible, and is cost-effective. In this study, the scaffolds were fabricated by blending DC with PCL in various ratios and applied non-solvent-induced phase separation (NIPS) and thermal-induced phase separation (TIPS) (N-TIPS), solvent casting and particulate leaching (SCPL), and gas foaming method to fabricate macro- and microporous structure. The characterization of the fabricated scaffolds was carried out by morphological analysis, bioactivity test, physicochemical analysis, and mechanical test. In vitro study was carried out by viability test, morphology observation, and gene expression. The results showed that the incorporation of DC enhances the physicochemical and mechanical properties of the scaffolds. Also, a large amount of bone mimetic apatite was formed according to the DC content in the bioactivity test. The in vitro study showed that the PCL/DC scaffold is biocompatible and the existence of apatite and DC formed a favorable microenvironment for cell proliferation and differentiation. Overall, the novel porous PCL/DC scaffold can be a promising biomaterial model for bone tissue engineering and regeneration.

Fabrication and Molecular Modeling of Navette-Shaped Fullerene Nanorods Using Tobacco Mosaic Virus as a Nanotemplate.

To date, metallization studies have been performed with the nanometer-scale template, Tobacco Mosaic Virus (TMV). Here we show that fullerenes as well can be deposited on TMV coat protein in a controlled manner. Two methods were followed for the coating process. First, underivatized fullerene was dispersed in different solvents to bring the underivatized fullerene and wild-type TMV together. Improved depositions were obtained with the fullerene dicarboxylic derivative synthesized via the Bingel method. The form of the coating was analyzed by transmission electron microscopy. Our results demonstrate that the coating efficiency with the carboxy derivative was much better compared to the underivatized fullerene. The goal of coupling a carbon nanoparticle to a biological molecule, the viral coat of TMV, was achieved with the carboxy derivative of fullerene, resulting in the production of navette-shaped nanorods. The interactions between carboxyfullerenes and TMV were investigated through modeling with computational simulations and Gaussian-based density functional theory (DFT) calculations using the Gaussian09 program package. The theoretical calculations supported the experimental findings. This inexpensive and untroublesome method promises new fullerene hybrid nanomaterials in particular shapes and structures.

Decellularized liver ECM-based 3D scaffolds: Compositional, physical, chemical, rheological, thermal, mechanical, and in vitro biological evaluations.

The extracellular matrix (ECM) is involved in many critical cellular interactions through its biological macromolecules. In this study, a macroporous 3D scaffold originating from decellularized bovine liver ECM (dL-ECM), with defined compositional, physical, chemical, rheological, thermal, mechanical, and in vitro biological properties was developed. First, protocols were determined that effectively remove cells and DNA while ECM retains biological macromolecules collagen, elastin, sGAGs in tissue. Rheological analysis revealed the elastic properties of pepsin-digested dL-ECM. Then, dL-ECM hydrogel was neutralized, molded, formed into macroporous (~100-200 µm) scaffolds in aqueous medium at 37 °C, and lyophilized. The scaffolds had water retention ability, and were mechanically stable for at least 14 days in the culture medium. The findings also showed that increasing the dL-ECM concentration from 10 mg/mL to 20 mg/mL resulted in a significant increase in the mechanical strength of the scaffolds. The hemolysis test revealed high in vitro hemocompatibility of the dL-ECM scaffolds. Studies investigating the viability and proliferation status of human adipose stem cells seeded over a 2-week culture period have demonstrated the suitability of dL-ECM scaffolds as a cell substrate. Prospective studies may reveal the extent to which 3D dL-ECM sponges have the potential to create a biomimetic environment for cells.

A Fast and Reliable Method to Interpret Short-Term Mortality in Perforated Peptic Ulcer: Red Cell Distribution Width is Sensitive and Specific.

INTRODUCTION: Peptic ulcer is an important health problem worldwide with a prevalence of around 5%. Peptic ulcer perforation is a potentially mortal complication of peptic ulcer disease. We aimed to investigate the potential use of red cell distribution width as a prognostic marker in peptic ulcer perforation. METHODS: The files, operation notes, biochemical and hematological parameters, and prognosis of patients who were operated for a peptic ulcer perforation were reviewed in a retrospective cohort study. The relation of red cell distribution width (RDW) to main outcome in-hospital mortality was assessed. RESULTS: The mean age of the 172 patients was 40 ± 17.89. There were 158 (92%) males and 14 (8%) females. The in-hospital mortality was 8.7% (15/172). The median RDW in the group with mortality was 15.00 (interquartile range (IQR): 14.30-17.20) compared with the median RDW in the group with no mortality as 13.2 (IQR: 12.80-14.00, p ≤ 0.001). Receiver operator characteristic curves were plotted for RDW to identify nonsurvivors and yielded a significant area under the curve as 0.812 (95% confidence interval: 0.682-0.942). The sensitivity and specificity of RDW at a cutoff value of 14.25% were calculated with an accuracy of 81.98 (95% confidence interval: 75.40-87.41) as 80.00 (51.91-95.67) and 82.17 (75.27-87.81), respectively. CONCLUSION: Increased RDW may be of use to interpret mortality in patients with peptic ulcer perforation.

Preliminary assessment of an injectable extracellular matrix from decellularized bovine myocardial tissue.

The goal of this study was to develop an injectable form of decellularized bovine myocardial tissue matrix which could retain high levels of functional ECM molecules, and could gel at physiological temperature. Dissected ventricular tissue was processed by a detergent-based protocol, lyophilized, enzymatically-digested, and neutralized to form the injectable myocardial matrix (IMM). Histochemical analysis, DNA quantification, and agarose gel electrophoresis demonstrated the efficiency of the applied protocol. Chemical, thermal, morphological, and rheological characterization; protein and sulfated glycosaminoglycan (sGAG) content analysis were performed, in vitro biological properties were evaluated. An in vivo histocompatibility and biodegradability study was performed. Histochemistry revealed complete removal of myocardial cells. DNA content analysis revealed a significant decrease (87%) in the nuclear material, while protein and sGAG contents were highly preserved following decellularization. Soluble IMM was capable of turning into gel form at ∼37 °C, indicating selfassembling property. In vitro findings showed the biomaterial was noncytotoxic, nonhemolytic, and supported the attachment and proliferation of mesenchymal stem cells. In vivo study demonstrated IMM was well-tolerated by rats receiving subcutaneous injection. This work demonstrates that the IMM from decellularized bovine myocardial tissue has the potential for use as a feasible regenerative biomaterial in prospective tissue engineering and regenerative medicine studies.

Magneto-sensitive decellularized bone matrix with or without low frequency-pulsed electromagnetic field exposure for the healing of a critical-size bone defect.

Bioactive ECM-based materials mimic the complex composition and structure of natural tissues. Decellularized cancellous bone matrix (DBM) has potential for guiding new bone formation and accelerating the regeneration process. On the other hand, low frequency-pulsed electromagnetic field (LF-PEMF) has been shown to enhance the regeneration capacity of bone defects. The present study sought to explore the feasibility of using DBM and DBM/MNP, and LF-PEMF for treating critical-size bone defects. Firstly, decellularization protocol was optimized to obtain a bioactive DBM, then MNPs were incorporated. Later, the physical, chemical and biological properties of DBM and DBM/MNP were assessed in vitro. MNPs homogeneously distributed into the DBM were not found to be toxic to human osteoblast cultures. Finally, an in vivo study was carried out with DBM and DBM/MNP composites in a bilateral critical-size rat cranial defect model (n = 48) with or without LF-PEMF exposure for 45 and 90 days. The histomorphometric and radiographic evaluations revealed that, while the collagen (positive control) and Sham (negative control) groups showed high incidence of fibrous connective tissue together with low level of osteogenic activity, both the DBM and DBM/MNP-grafted groups significantly promoted new bone tissue formation and angiogenesis, by the appropriate use of LF-PEMF for 90 days.

Biomimetic 3D-Bone Tissue Model.

Various approaches have been evaluated for developing three-dimensional (3D) scaffolds for modeling or engineering of the bone tissue. However, most of such attempts have come up short in mimicking the natural bone tissue extracellular matrix (ECM) microenvironment, especially its natural bioactive content. Here we describe the methodology for the preparation of a natural ECM-based multichannel construct as a biomimetic 3D bone tissue model. We elucidate the construction of the composite scaffold incorporating decellularized small intestinal submucosa ECM, synthetic hydroxyapatite and poly(ε-caprolactone), and the mechanical stimulation of the cell-seeded construct under bioreactor culture.

The Effects of Intervening With Synonasal Changes on Headaches in Migraine Patients Using Endonasal Surgery.

OBJECTIVE: Some anatomical changes might trigger headaches in people who have migraine, and that surgical applications eliminating the structural problems in treatment-resistant migraine patients are effective in pain treatment. METHODS: A total of 36 patients, who did not respond to different treatment options without aura migraine and chronic migraine that were showing synonasal and anatomical changes in synonasal nasal endoscopy and/or paranasal sinus CT screening, responding insufficiently and/or approximately one year period also did not respond to different treatment options, were included in this study between June 2016 and September 2019. RESULTS: The relation between migraine episodes and synonasal symptoms was found to be statistically significant. A significant difference was detected between nasal congestion and obstruction, postnasal discharge, and runny nose in patients with attacks compared to patients without attacks. The difference between mean pain severity values was statistically significant when compared to preoperative values (3.0(3.0∼4.0)) and post-operative values (1.0(0∼1.0)). When the pain severity after the operation (1.0(1.0∼2.75)) was compared with the severity of pain before the operation (5.0 (3.0∼5.0)), it was determined that there was a significant decrease in pain severity in patients diagnosed with chronic migraine, the difference between the mean pain severity values was statistically significant, and the prevalence of pain decreased at a significant level after the operation. CONCLUSION: The results of the present study indicate that the elimination of synonasal structural changes, which were hypothesized to trigger pain in migraine patients, could have a pain-reducing effect on the frequency and severity of the pain.