scholarly journals In vivo feasibility study of the use of porous polyhedral oligomeric silsesquioxane implants in partial laryngeal reconstruction

2019 ◽  
Author(s):  
Martin A. Birchall ◽  
Peggy Herrmann ◽  
Paul Sibbons
Keyword(s):  
Epithelial Cells ◽  
Thyroid Cartilage ◽  
Unmet Need ◽  
Polyhedral Oligomeric Silsesquioxane ◽  
Present Formulation ◽  
Post Surgery ◽  
Oligomeric Silsesquioxane ◽  
Post Implantation

AbstractBackgroundLoss of substantial volumes of laryngeal tissue after trauma or cancer significantly impairs quality of life. We hypothesised that repair of laryngeal defects with a candidate biomaterial, seeded with mesenchymal stem cells (MSC) and epithelial cells, may offer a therapeutic approach to this unmet need.MethodMoulded porous polyhedral oligomeric silsesquioxane polycarbonate-urea (POSS-PCU) scaffolds were seeded with human-derived MSC and epithelial cells, were implanted orthotopically into a defect created in the thyroid cartilage in eight pigs and monitoredin vivofor 2 months.In vivoassessments were performed at 1, 2, 4 and 8 weeks post implantation. Histology was performed following termination.ResultsImplant operations were uncomplicated. One pig was terminated early (2 weeks post-implantation) following expectoration of its implant. No other mortality or morbidity was observed. Endoscopy showed partial extrusion of implants at two weeks and complete extrusion of all implants by termination.ConclusionsPOSS-PCU moulded laryngeal implants, in the present formulation, are extruded from the site of implantation between two- and eight-weeks post-surgery in pigs. In its present formulation and with the present, one-stage, protocol, this material does not appear to provide a suitable scaffold and vehicle for cells intended for partial laryngeal replacement in pigs.

scholarly journals Influence of calcium ion-modified implant surfaces in protein adsorption and implant integration

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Eduardo Anitua ◽  
Andreia Cerqueira ◽  
Francisco Romero-Gavilán ◽  
Iñaki García-Arnáez ◽  
Cristina Martinez-Ramos ◽  
...  
Keyword(s):  
Protein Adsorption ◽  
Titanium Implant ◽  
Volume Density ◽  
Bone Implant ◽  
The Mean ◽  
Intervention Costs ◽  
Medial Section ◽  
Post Implantation

Abstract Background Calcium (Ca) is a well-known element in bone metabolism and blood coagulation. Here, we investigate the link between the protein adsorption pattern and the in vivo responses of surfaces modified with calcium ions (Ca-ion) as compared to standard titanium implant surfaces (control). We used LC–MS/MS to identify the proteins adhered to the surfaces after incubation with human serum and performed bilateral surgeries in the medial section of the femoral condyles of 18 New Zealand white rabbits to test osseointegration at 2 and 8 weeks post-implantation (n=9). Results Ca-ion surfaces adsorbed 181.42 times more FA10 and 3.85 times less FA12 (p<0.001), which are factors of the common and the intrinsic coagulation pathways respectively. We also detected differences in A1AT, PLMN, FA12, KNG1, HEP2, LYSC, PIP, SAMP, VTNC, SAA4, and CFAH (p<0.01). At 2 and 8 weeks post-implantation, the mean bone implant contact (BIC) with Ca-ion surfaces was respectively 1.52 and 1.25 times higher, and the mean bone volume density (BVD) was respectively 1.35 and 1.13 times higher. Differences were statistically significant for BIC at 2 and 8 weeks and for BVD at 2 weeks (p<0.05). Conclusions The strong thrombogenic protein adsorption pattern at Ca-ion surfaces correlated with significantly higher levels of implant osseointegration. More effective implant surfaces combined with smaller implants enable less invasive surgeries, shorter healing times, and overall lower intervention costs, especially in cases of low quantity or quality of bone.

scholarly journals Chondrogenically Primed Human Mesenchymal Stem Cells Persist and Undergo Early Stages of Endochondral Ossification in an Immunocompetent Xenogeneic Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Niamh Fahy ◽  
Virginia Palomares Cabeza ◽  
Andrea Lolli ◽  
Janneke Witte-Bouma ◽  
Ana Merino ◽  
...  
Keyword(s):  
T Cells ◽  
Bone Formation ◽  
Immune Cells ◽  
Endochondral Ossification ◽  
Human Mscs ◽  
Early Stages ◽  
Post Surgery ◽  
The Impact ◽  
Post Implantation

Tissue engineering approaches using progenitor cells such as mesenchymal stromal cells (MSCs) represent a promising strategy to regenerate bone. Previous work has demonstrated the potential of chondrogenically primed human MSCs to recapitulate the process of endochondral ossification and form mature bone in vivo, using immunodeficient xenogeneic models. To further the translation of such MSC-based approaches, additional investigation is required to understand the impact of interactions between human MSC constructs and host immune cells upon the success of MSC-mediated bone formation. Although human MSCs are considered hypoimmunogenic, the potential of chondrogenically primed human MSCs to induce immunogenic responses in vivo, as well as the efficacy of MSC-mediated ectopic bone formation in the presence of fully competent immune system, requires further elucidation. Therefore, the aim of this study was to investigate the capacity of chondrogenically primed human MSC constructs to persist and undergo the process of endochondral ossification in an immune competent xenogeneic model. Chondrogenically differentiated human MSC pellets were subcutaneously implanted to wild-type BALB/c mice and retrieved at 2 and 12 weeks post-implantation. The percentages of CD4+ and CD8+ T cells, B cells, and classical/non-classical monocyte subsets were not altered in the peripheral blood of mice that received chondrogenic MSC constructs compared to sham-operated controls at 2 weeks post-surgery. However, MSC-implanted mice had significantly higher levels of serum total IgG compared to sham-operated mice at this timepoint. Flow cytometric analysis of retrieved MSC constructs identified the presence of T cells and macrophages at 2 and 12 weeks post-implantation, with low levels of immune cell infiltration to implanted MSC constructs detected by CD45 and CD3 immunohistochemical staining. Despite the presence of immune cells in the tissue, MSC constructs persisted in vivo and were not degraded/resorbed. Furthermore, constructs became mineralised, with longitudinal micro-computed tomography imaging revealing an increase in mineralised tissue volume from 4 weeks post-implantation until the experimental endpoint at 12 weeks. These findings indicate that chondrogenically differentiated human MSC pellets can persist and undergo early stages of endochondral ossification following subcutaneous implantation in an immunocompetent xenogeneic model. This scaffold-free model may be further extrapolated to provide mechanistic insight to osteoimmunological processes regulating bone regeneration and homeostasis.

A polyhedral oligomeric silsesquioxane/molecular sieve codoped molecularly imprinted polymer for gastroretentive drug-controlled release in vivo

2018 ◽  
Vol 6 (12) ◽  
pp. 3170-3177 ◽  
Author(s):  
Xu Wang ◽  
Fang-Fang Yang ◽  
Li-Ping Zhang ◽  
Yan-Ping Huang ◽  
Zhao-Sheng Liu
Keyword(s):  
Controlled Release ◽  
Molecularly Imprinted Polymer ◽  
Molecular Sieve ◽  
Polyhedral Oligomeric Silsesquioxane ◽  
Imprinted Polymer ◽  
Molecularly Imprinted ◽  
Drug Controlled Release ◽  
Oligomeric Silsesquioxane ◽  
Co Doped

A novel molecularly imprinted polymer co-doped by polyhedral oligomeric silsesquioxane and molecular sieve for gastroretentive drug-controlled release.

scholarly journals Patient Derived Colonoids as Drug Testing Platforms–Critical Importance of Oxygen Concentration

2021 ◽  
Vol 12 ◽  
Author(s):  
Helene Kolstad Skovdahl ◽  
Shreya Gopalakrishnan ◽  
Tarjei Dahl Svendsen ◽  
Atle van Beelen Granlund ◽  
Ingunn Bakke ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Oxygen Concentration ◽  
Intestinal Epithelium ◽  
Drug Testing ◽  
Unmet Need ◽  
Test System ◽  
Healthy Controls ◽  
Intestinal Organoids ◽  
Experimental Pharmacology

Treatment of inflammatory bowel disease (IBD) is challenging, with a series of available drugs each helping only a fraction of patients. Patients may face time-consuming drug trials while the disease is active, thus there is an unmet need for biomarkers and assays to predict drug effect. It is well known that the intestinal epithelium is an important factor in disease pathogenesis, exhibiting physical, biochemical and immunologic driven barrier dysfunctions. One promising test system to study effects of existing or emerging IBD treatments targeting intestinal epithelial cells (IECs) is intestinal organoids (“mini-guts”). However, the fact that healthy intestinal epithelium is in a physiologically hypoxic state has largely been neglected, and studies with intestinal organoids are mainly performed at oxygen concentration of 20%. We hypothesized that lowering the incubator oxygen level from 20% to 2% would recapitulate better the in vivo physiological environment of colonic epithelial cells and enhance the translational value of intestinal organoids as a drug testing platform. In the present study we examine the effects of the key IBD cytokines and drug targets TNF/IL17 on human colonic organoids (colonoids) under atmospheric (20%) or reduced (2%) O2. We show that colonoids derived from both healthy controls and IBD-patients are viable and responsive to IBD-relevant cytokines at 2% oxygen. Because chemokine release is one of the important immunoregulatory traits of the epithelium that may be fine-tuned by IBD-drugs, we also examined chemokine expression and release at different oxygen concentrations. We show that chemokine responses to TNF/IL17 in organoids display similarities to inflamed epithelium in IBD-patients. However, inflammation-associated genes induced by TNF/IL17 were attenuated at low oxygen concentration. We detected substantial oxygen-dependent differences in gene expression in untreated as well as TNF/IL17 treated colonoids in all donors. Further, for some of the IBD-relevant cytokines differences between colonoids from healthy controls and IBD patients were more pronounced in 2% O2 than 20% O2. Our results strongly indicate that an oxygen concentration similar to the in vivo epithelial cell environment is of essence in experimental pharmacology.

Shall I trust you? From child human-robot interaction to trusting relationships

2019 ◽  
Author(s):  
Cinzia Di Dio ◽  
Federico Manzi ◽  
Giulia Peretti ◽  
Angelo Cangelosi ◽  
Paul L. Harris ◽  
...  
Keyword(s):  
Behavioral Pattern ◽  
Human Robot Interaction ◽  
School Age Children ◽  
Social Relevance ◽  
Robot Interaction ◽  
Cognitive Correlates ◽  
The Social ◽  
The Relationship

Studying trust within human-robot interaction is of great importance given the social relevance of robotic agents in a variety of contexts. We investigated the acquisition, loss and restoration of trust when preschool and school-age children played with either a human or a humanoid robot in-vivo. The relationship between trust and the quality of attachment relationships, Theory of Mind, and executive function skills was also investigated. No differences were found in children’s trust in the play-partner as a function of agency (human or robot). Nevertheless, 3-years-olds showed a trend toward trusting the human more than the robot, while 7-years-olds displayed the reverse behavioral pattern, thus highlighting the developing interplay between affective and cognitive correlates of trust.

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