Patient-derived xenografts (PDXs) can be improved by implantation of a humanized niche. Nevertheless, the overall complexity of the current protocols, as well as the use of specific biomaterials and procedures, limits the wider adoption of this approach. Here, we identify the essential minimum steps required to create the humanized scaffolds and achieve successful acute myeloid leukemia (AML) engraftment. We compared seven biomaterials, which included both published and custom-designed materials. The highest level of bone marrow niche was achieved with extracellular matrix gels and custom collagen fiber, both of which allowed for a simple non-surgical implantation. The biomaterial selection did not influence the following AML infiltration. Regarding xenotransplantation, standard intravenous administration produced the most robust engraftment, even for two out of four otherwise non-engrafting AML samples. In contrast, direct intra-scaffold xenotransplantation did not offer any advantage. In summary, we demonstrate that the combination of an injectable biomaterial for scaffold creation plus an intravenous route for AML xenotransplantation provide the most convenient and robust approach to produce AML PDX using a humanized niche.
- MeSH
- akutní myeloidní leukemie * patologie MeSH
- biokompatibilní materiály * farmakologie aplikace a dávkování MeSH
- heterografty MeSH
- lidé MeSH
- myši SCID MeSH
- myši MeSH
- tkáňové podpůrné struktury * chemie MeSH
- transplantace heterologní * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Material-induced ossification is suggested as a suitable approach to heal large bone defects. Fiber-reinforced composite-bioactive glasses (FRC-BGs) display properties that could enhance the ossification of calvarial defects. Here, we analyzed the healing processes of a FRC-BG implant in vivo from the perspective of material-induced ossification. Histological analysis of the implant, which was removed 5 months after insertion, showed the formation of viable, noninflammatory mesenchymal tissue with newly-formed mineralized woven bone, as well as nonmineralized connective tissue with capillaries and larger blood vessels. The presence of osteocytes was detected within the newly generated bone matrix. To expand our understanding on the osteogenic properties of FRC-BG, we cultured human adipose tissue-derived mesenchymal stromal cells (AD-MSCs) in the presence of two different BGs (45S5 and S53P4) and Al2 O3 control. AD-MSCs grew and proliferated on all the scaffolds tested, as well as secreted abundant extracellular matrix, when osteogenic differentiation was appropriately stimulated. 45S5 and S53P4 induced enhanced expression of COL2A1, COL10A1, COL5A1 collagen subunits, and pro-osteogenic genes BMP2 and BMP4. The concomitant downregulation of BMP3 was also detected. Our findings show that FRC-BG can support the vascularization of the implant and the formation of abundant connective tissue in vivo. Specifically, BG 45S5 and BG S53P4 are suited to evoke the osteogenic potential of host mesenchymal stromal cells. In conclusion, FRC-BG implant demonstrated material-induced ossification both in vitro and in vivo.
- MeSH
- biokompatibilní materiály aplikace a dávkování MeSH
- lebka zranění metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- osteogeneze účinky léků MeSH
- protézy a implantáty * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
PURPOSE OF THE STUDY Cranioplasty is currently the most common neurosurgical procedure. The purpose of this study is to describe the first experience with successful use of the Cranio-Oss (PEEK) custom implant for cranioplasty. MATERIAL AND METHODS In the period 2012 to 2013, a total of 26 cranioplasties were performed. In fourteen patients, their own bone flap was used for reconstruction. In four cases, a synthetic Cranio-Oss bone implant made of PEEK was used. In six patients, the defect was covered by an intraoperatively-made Palacos implant and in two cases, minor defects were covered with a titanium mesh. The patients were followed up for at least five years. Cranio-Oss is a cranial implant made from polyetheretherketone (PEEK), a synthetic biocompatible material. The implant is created using the CAD/CAM method in the shape of the bone defect based on the CT scan. Creating optimal roughness of the implant surface and of the surface of the contact area attached to the bone bed is controlled and included already in the strategy for machining individual areas of the implant during its manufacturing at a 5-axis machining centre. RESULTS The Cranio-Oss implant was used in four younger patients to cover larger and complex-shaped defects. The mean age of patients in this group was 47 years. The implant was fixed to the skull by micro-plates. In all the cases the wound healed well with good cosmetic results without the necessity of revision with respect to the used implant. The follow-up CT scans always showed the implant in situ with no signs of malposition. DISCUSSION Autologous bone flap is the most suitable material for defect reconstruction after craniectomy. This option is affordable and represents one of the best methods of reconstruction of defects after craniectomy in terms of cosmetic results. In some cases, the original skull cannot be used for cranioplasty (e.g. if destructed by tumourous process, infected or in comminuted fractures). In such cases, the defect needs to be managed using a synthetic implant. In case of extensive defects, the most suitable option is a custom made implant from advanced biomaterials. CONCLUSIONS Authors prefer using autologous bone flaps during cranioplasty. In cases where this method is unavailable, a synthetic bone substitute has to be used. The first medium-term experience with the use of a Cranio-Oss implant made of PEEK showed that it is a suitable alternative to the patient's own bone. No complications associated with this synthetic implant were reported and its use to manage skull defects can be strongly recommended. With respect to legal and accreditationrelated difficulties connected with bone fragments storage and thanks to the continuous cost reduction of synthetic implants will their importance grow in the future. Key words: decompressive craniectomy, bone substitute, craniotrauma.
- MeSH
- biokompatibilní materiály aplikace a dávkování MeSH
- ketony aplikace a dávkování MeSH
- lebka chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- polyethylenglykoly aplikace a dávkování MeSH
- protézy a implantáty MeSH
- retrospektivní studie MeSH
- zákroky plastické chirurgie přístrojové vybavení metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Injectable hydrogels that aim to mechanically stabilise the weakened left ventricle wall to restore cardiac function or to deliver stem cells in cardiac regenerative therapy have shown promising data. However, the clinical translation of hydrogel-based therapies has been limited due to difficulties injecting them through catheters. We have engineered a novel catheter, Advanced Materials Catheter (AMCath), that overcomes translational hurdles associated with delivering fast-gelling covalently cross-linked hyaluronic acid hydrogels to the myocardium. We developed an experimental technique to measure the force required to inject such hydrogels and determined the mechanical/viscoelastic properties of the resulting hydrogels. The preliminary in vivo feasibility of delivering fast-gelling hydrogels through AMCath was demonstrated by accessing the porcine left ventricle and showing that the hydrogel was retained in the myocardium post-injection (three 200 μL injections delivered, 192, 204 and 183 μL measured). However, the mechanical properties of the hydrogels were reduced by passage through AMCath (≤20.62% reduction). We have also shown AMCath can be used to deliver cardiopoietic adipose-derived stem cell-loaded hydrogels without compromising the viability (80% viability) of the cells in vitro. Therefore, we show that hydrogel/catheter compatibility issues can be overcome as we have demonstrated the minimally invasive delivery of a fast-gelling covalently cross-linked hydrogel to the beating myocardium.
- MeSH
- biokompatibilní materiály aplikace a dávkování MeSH
- buněčné linie MeSH
- design vybavení MeSH
- hydrogely aplikace a dávkování MeSH
- imobilizované buňky cytologie transplantace MeSH
- infarkt myokardu terapie MeSH
- injekce MeSH
- kmenové buňky cytologie MeSH
- kyselina hyaluronová aplikace a dávkování MeSH
- lékové transportní systémy přístrojové vybavení MeSH
- lidé MeSH
- prasata MeSH
- reagencia zkříženě vázaná aplikace a dávkování MeSH
- srdeční katétry * MeSH
- transplantace kmenových buněk MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- biokompatibilní materiály * aplikace a dávkování terapeutické užití MeSH
- chirurgie operační metody MeSH
- dospělí MeSH
- fraktury kostí chirurgie terapie MeSH
- hojení fraktur * MeSH
- lidé středního věku MeSH
- lidé MeSH
- protézy a implantáty MeSH
- sklo * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Tissue engineering (TE) and regenerative medicine are progressively developed areas due to many novel tissue replacements and implementation strategies. Increasing knowledge involving the fabrication of biomaterials with advanced physicochemical and biological characteristics, successful isolation and preparation of stem cells, incorporation of growth and differentiation factors, and biomimetic environments gives us a unique opportunity to develop various types of scaffolds for TE. The current strategies for soft tissue reconstitution or regeneration highlight the importance of novel regenerative therapies in cases of significant soft tissue loss and in cases of congenital defects, disease, trauma and ageing. Various types of biomaterials and scaffolds have been tested for soft tissue regeneration. The synthetic types of materials have gained great attention due to high versatility, tunability and easy functionalization for better biocompatibility. This article reviews the current materials that are usually the most used for the fabrication of scaffolds for soft TE; in addition, the types of scaffolds together with examples of their applications for the regenerative purposes of soft tissue, as well as their major physicochemical characteristics regarding the increased applicability of these materials in medicine, are reviewed.
- MeSH
- biokompatibilní materiály aplikace a dávkování metabolismus MeSH
- lidé MeSH
- polymery aplikace a dávkování metabolismus MeSH
- poranění měkkých tkání farmakoterapie metabolismus MeSH
- stárnutí účinky léků fyziologie MeSH
- tkáňové inženýrství metody trendy MeSH
- tkáňové podpůrné struktury * trendy MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The objective is to compare the long-term voice outcomes of vocal fold augmentation (VFA) using autologous fat injection via direct microlaryngoscopy versus office-based calcium hydroxylapatite (CaHA) injection. Patients with glottal insufficiency and a gap no greater than 3 mm caused by unilateral vocal fold paralysis or vocal fold atrophy were prospectively recruited to the study from September 2012 to September 2015. From September 2012 to May 2014, VFA was only performed using autologous fat via direct microlaryngoscopy under general anesthesia (N = 14). From May 2014 to September 2015, VFA was performed as an office-based procedure using a transoral approach to inject CaHA (N = 17). Videolaryngostroboscopic evaluation, subjective satisfaction with voice, voice handicap index (VHI), and maximal phonation time (MPT) were analyzed pre-injection and 12 months after VFA. A total of 31 patients were analyzed. One year after VFA, 67.8% of the patients were satisfied with their voice, with no significant difference between groups (P = 0.247). The mean improvement in VHI in the autologous fat group was 31.6 ± 16.82 versus 35 ± 27.24 in the CaHA group (P = 0.664). MPT improvement was also similar in the two groups: 5.5 ± 2.52 for the autologous fat group versus 6.0 ± 3.98 for the CaHA group (P = 0.823). Both autologous fat injection via direct microlaryngoscopy and office-based CaHA injection have good long-term results. There were no differences in the treatment results of the two procedures 1 year after injection.
- MeSH
- atrofie MeSH
- biokompatibilní materiály aplikace a dávkování MeSH
- dlouhodobé vedlejší účinky * diagnóza etiologie patofyziologie MeSH
- dospělí MeSH
- hlasové řasy * patologie patofyziologie chirurgie MeSH
- hydroxyapatit aplikace a dávkování MeSH
- injekce MeSH
- kvalita hlasu * MeSH
- laryngoskopie metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- ochrnutí hlasivek * diagnóza chirurgie MeSH
- srovnávací výzkum účinnosti MeSH
- tuková tkáň transplantace MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
For biodegradable porous scaffolds to have a potential application in cartilage regeneration, they should enable cell growth and differentiation and should have adequate mechanical properties. In this study, our aim was to prepare biocompatible scaffolds with improved biomechanical properties. To this end, we have developed foam scaffolds from poly-epsilon-caprolactone (PCL) with incorporated chitosan microparticles. The scaffolds were prepared by a salt leaching technique from either 10 or 15 wt% PCL solutions containing 0, 10 and 20 wt% chitosan microparticles, where the same amount and size of NaCl was used as a porogen in all the cases. PCL scaffolds without and with low amounts of chitosan (0 and 10 wt% chitosan) showed higher DNA content than scaffolds with high amounts of chitosan during a 22-day experiment. 10 wt% PCL with 10 and 20 wt% chitosan showed significantly increased viscoelastic properties compared to 15 wt% PCL scaffolds with 0 and 10 wt% chitosan. Thus, 10 wt% PCL scaffolds with 0 wt% and 10 wt% chitosan are potential scaffolds for cartilage regeneration.
- MeSH
- biokompatibilní materiály aplikace a dávkování chemie MeSH
- chrupavka cytologie fyziologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikrosféry * MeSH
- polyestery aplikace a dávkování chemie MeSH
- proliferace buněk účinky léků fyziologie MeSH
- řízená tkáňová regenerace metody MeSH
- tkáňové podpůrné struktury * MeSH
- viabilita buněk účinky léků fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
As an Extracellular Matrix (ECM) component, Hyaluronic acid (HA) plays a multi-faceted role in cell migration, proliferation and differentiation at micro level and system level events such as tissue water homeostasis. Among its biological functions, it is known to interact with cytokines and contribute to their retention in ECM microenvironment. In addition to its biological functions, it has advantageous physical properties which result in the industrial endeavors in the synthesis and extraction of HA for variety of applications ranging from medical to cosmetic. Recently, HA and its derivatives have been the focus of active research for applications in biomedical device coatings, drug delivery systems and in the form of scaffolds or cell-laden hydrogels for tissue engineering. A specific reason for the increase in use of HA based structures is their immunomodulatory and regeneration inducing capacities. In this context, this article reviews recent literature on modulation of the implantable biomaterial microenvironment by systems based on HA and its derivatives, particularly hydrogels and microscale coatings that are able to deliver cytokines in order to reduce the adverse immune reactions and promote tissue healing.
- MeSH
- biokompatibilní materiály aplikace a dávkování MeSH
- hojení ran účinky léků MeSH
- hydrogely aplikace a dávkování MeSH
- imunomodulace účinky léků MeSH
- kyselina hyaluronová aplikace a dávkování MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- regenerativní lékařství metody MeSH
- tkáňové inženýrství metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION AND HYPOTHESIS: Information on urethral bulking therapy in women after previous pelvic radiotherapy is lacking. This study compared the safety and efficacy of polyacrylamide intraurethral injections in patients with and without previous radiotherapy. METHODS: A total of 46 patients with severe stress urinary incontinence (SUI) were enrolled in this multicenter prospective trial. Group A consisted of 24 patients with previous radiotherapy to the pelvis for the treatment of a gynaecological malignancy. Group B consisted of 22 patients without previous radiotherapy. All patients were treated with a transurethral injection of a bulking solution (Bulkamid). The average follow-up was 12.4 months. The paired Wilcoxon test was used to compare the results before and after the procedure within the groups, and the two-sample Wilcoxon test was used for comparisons between groups. RESULTS: Complete continence was achieved in 25 % of patients in group A and in 36.4 % of patients in group B. Significantly reduced urine leakage was observed in both groups (p = 0.0164 in group A and p = 0.0002 in group B). The total scores in the International Consultation on Incontinence Questionnaire decreased by 5.2 in group A (p = 0.0000) and 6.36 in group B (p = 0.0001). The scores for the Total Patient Perception of Bladder Condition decreased by 1.54 in group A (p = 0.0001) and 2.59 in group B (p = 0.0000), with a significant difference between groups (p = 0.0224). No clinically significant changes in urodynamic parameters were observed. No severe adverse events were noted. CONCLUSIONS: Based on our results, we conclude that urethral bulking therapy is a valuable treatment option in patients with severe SUI who have undergone pelvic radiotherapy for the treatment of gynaecological malignancy.
- MeSH
- akrylové pryskyřice aplikace a dávkování škodlivé účinky MeSH
- biokompatibilní materiály aplikace a dávkování škodlivé účinky MeSH
- dospělí MeSH
- hydrogely aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory ženských pohlavních orgánů komplikace radioterapie MeSH
- prospektivní studie MeSH
- průzkumy a dotazníky MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stresová inkontinence moči komplikace farmakoterapie patofyziologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH