Oral surgery in people with inherited bleeding disorder: A retrospective study.

INTRODUCTION: The objectives were to describe the peri-operative management of people with inherited bleeding disorders in oral surgery and to investigate the association between type of surgery and risk of developing bleeding complications. MATERIALS AND METHODS: This retrospective observational study included patients with haemophilia A or B, von Willebrand disease, Glanzmann thrombasthenia or isolated coagulation factor deficiency such as afibrinogenemia who underwent osseous (third molar extraction, ortho-surgical traction, dental implant placement) or nonosseous oral surgery between 2014 and 2021 at Bordeaux University Hospital (France). Patients and oral surgery characteristics were retrieved from medical records. Odds ratio (OR) and 95% confidence interval (CI) were estimated using logistic regression. RESULTS: Of the 83 patients included, general anaesthesia was performed in 16%. Twelve had a bleeding complication (14.5%) including six after osseous surgery. The most serious complication was the appearance of anti-FVIII inhibitor in a patient with moderate haemophilia A. All bleeding complications were managed by a local treatment and factor injections where indicated. No association was observed between type of surgery (osseous vs. nonosseous) and risk of bleeding complications after controlling for sex, age, disease type and severity, multiple extractions, type of anaesthesia and use of fibrin glue (OR: 3.21, 95% CI: .69-14.88). CONCLUSION: In this study, we have observed that bleeding complications after oral surgery in people with inherited bleeding disorders were moderately frequent and easily managed. However, in this study, we observed a serious complication highlighting the necessity of a thorough benefit-risk balance evaluation during the preoperative planning of the surgical and medical protocol.

Critères influençant le choix du premier poste après l'internat de chirurgie orale en France.

INTRODUCTION: The Specialized Diploma in Oral Surgery (Diplôme d’études spécialisées en chirurgie orale) was established in 2011. It gives its holders a unique combination of medical and surgical expertise. As a specialty, oral surgery can be pursued via both medical and dental pathways. However, the criteria guiding students’ choice of first job after residency remain largely unknown. PURPOSE OF THE RESEARCH: The primary objective was to evaluate the factors influencing students’ choice of first job after completing their oral surgery residency. RESULTS: The main geographical factors influencing job choice were the presence of family or friends, a short commute, and the location of the spouse’s place of work. Key practice conditions included access to advanced technical facilities and an operating theater offering general anesthesia. Clinical activities ranged from pre-implant grafts to general oral surgery. The likelihood of pursuing a hospital-based position in the same facility was correlated with the well-being experienced during the residency (p < 0.05) and with the oral surgeons’ medical background (p = 0.001). Significant associations exist between region of origin, internship location, and practice region (p < 0.001; p <0.001). CONCLUSIONS: The main factors influencing the choice of first position after oral surgery residency depend on family-related and technical criteria.

Vascularization of Cell-Laden Microfibres by Femtosecond Laser Processing.

To face the increasing demand for organ transplantation, currently the development of tissue engineering appears as the best opportunity to effectively regenerate functional tissues and organs. However, these approaches still face the lack of an efficient method to produce an efficient vascularization system. To answer these issues, the formation of an intra-volume channel within a three-dimensional, scaffold free, mature, and cell-covered collagen microfibre is here investigated through laser-induced cavitation. An intra-volume channel was formed upon irradiation with a near-infrared, femtosecond laser beam, focused with a high numerical aperture lens. The laser beam directly crossed the surface of a dense and living-cell bilayer and was focused behind the bilayer to induce channel formation in the hydrogel core while preserving the cell bilayer. Channel formation was assessed through confocal microscopy. Channel generation inside the hydrogel core was enhanced by the formation of voluminous cavitation bubbles with a lifetime longer than 30 s, which also improved intra-volume channel durability. Twenty-four hours after laser processing, cellular viability dropped due to a lack of sufficient hydration for processing longer than 10 min. However, the processing automation could drastically reduce the cellular mortality, this way enabling the formation of hollowed microfibres with a high density of living-cell outer bilayer.

Intra-volume processing of gelatine hydrogel by femtosecond laser-induced cavitation.

Cell oxygenation and nutrition are crucial for the viability of tissue-engineered constructs, and different alternatives are currently being developed to achieve an adequate vascularisation of the engineered tissue. One of the alternatives is the generation of channel-like patterns in a bioconstruct. Here, the formation of full-formed channels inside hydrogels by laser-induced cavitation was investigated. A near-infrared, femtosecond laser beam focused with a high numerical aperture was employed to obtain intra-volume modifications of a block of gelatine hydrogel. Characterisation of the laser-processed gelatine was carried out by optical microscopy and epifluorescence microscopy right after and 24 h after the laser process. Rheology analyses on the unprocessed gelatine blocks were conducted to better understand the cavitation mechanism taking place during the intense laser interaction. Different cavitation patterns were observed at varying dose values by changing the repetition rate and the overlap between successive pulses while keeping the laser fluence and the number of passes fixed. This way, cavitation bubble features and behaviour can be controlled to optimise the formation of intra-volume channels in the gelatine volume. Results showed that the generation of fully formed channels was linked to the formation of large non-spherical cavitation bubbles during the laser interaction at high dose and low repetition rates. In conclusion, the formation of fully formed channels was made possible with a near-infrared, femtosecond laser beam strongly focused inside gelatine hydrogel blocks through laser-induced cavitation at high dose and low repetition rates.

Towards an in vitro model of the glomerular barrier unit with an innovative bioassembly method.

BACKGROUND: The development of an artificial glomerular unit may be pivotal for renal pathophysiology studies at a multicellular scale. Using a tissue engineering approach, we aimed to reproduce in part the specific glomerular barrier architecture by manufacturing a glomerular microfibre (Mf). METHODS: Immortalized human glomerular cell lines of endothelial cells (GEnCs) and podocytes were used. Cells and a three-dimensional (3D) matrix were characterized by immunofluorescence with confocal analysis, Western blot and polymerase chain reaction. Optical and electron microscopy were used to study Mf and cell shapes. We also analysed cell viability and cell metabolism within the 3D construct at 14 days. RESULTS: Using the Mf manufacturing method, we repeatedly obtained a cellularized Mf sorting human glomerular cells in 3D. Around a central structure made of collagen I, we obtained an internal layer composed of GEnC, a newly formed glomerular basement membrane rich in α5 collagen IV and an external layer of podocytes. The cell concentration, optimal seeding time and role of physical stresses were modulated to obtain the Mf. Cell viability and expression of specific proteins (nephrin, synaptopodin, vascular endothelial growth factor receptor 2 (VEGFR2) and von Willebrandt factor (vWF)) were maintained for 19 days in the Mf system. Mf ultrastructure, observed with EM, had similarities with the human glomerular barrier. CONCLUSION: In summary, with our 3D bio-engineered glomerular fibre, GEnC and podocytes produced a glomerular basement membrane. In the future, this glomerular Mf will allow us to study cell interactions in a 3D system and increase our knowledge of glomerular pathophysiology.

Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations.

BACKGROUND: Amelogenesis imperfecta (AI) is a group of genetic diseases characterised by tooth enamel defects. AI was recently described in patients with familial hypercalciuria and hypomagnesaemia with nephrocalcinosis (FHHNC) caused by CLDN16 mutations. In the kidney, claudin-16 interacts with claudin-19 to control the paracellular passage of calcium and magnesium. FHHNC can be linked to mutations in both genes. Claudin-16 was shown to be expressed during amelogenesis; however, no data are available on claudin-19. Moreover, the enamel phenotype of patients with CLDN19 mutations has never been described. In this study, we describe the clinical and genetic features of nine patients with FHHNC carrying CLDN19 mutations and the claudin-19 expression profile in rat ameloblasts. METHODS: Six FHHNC Brazilian patients were subjected to mutational analysis. Three additional French patients were recruited for orodental characterisation. The expression profile of claudin-19 was evaluated by RT-qPCR and immunofluorescence using enamel epithelium from rat incisors. RESULTS: All patients presented AI at different degrees of severity. Two new likely pathogenic variations in CLDN19 were found: p.Arg200Gln and p.Leu90Arg. RT-qPCR revealed low Cldn19 expression in ameloblasts. Confocal analysis indicated that claudin-19 was immunolocalised at the distal poles of secretory and maturing ameloblasts. CONCLUSIONS: For the first time, it was demonstrated that AI is associated with FHHNC in patients carrying CLDN19 mutations. The data suggest claudin-19 as an additional determinant in enamel formation. Indeed, the coexistence of hypoplastic and hypomineralised AI in the patients was consistent with claudin-19 expression in both secretory and maturation stages. Additional indirect systemic effects cannot be excluded.

Human amniotic membrane for guided bone regeneration of calvarial defects in mice.

Due to its biological properties, human amniotic membrane (hAM) is widely studied in the field of tissue engineering and regenerative medicine. hAM is already very attractive for wound healing and it may be helpful as a support for bone regeneration. However, few studies assessed its potential for guided bone regeneration (GBR). The purpose of the present study was to assess the potential of the hAM as a membrane for GBR. In vitro, cell viability in fresh and cryopreserved hAM was assessed. In vivo, we evaluated the impact of fresh versus cryopreserved hAM, using both the epithelial or the mesenchymal layer facing the defect, on bone regeneration in a critical calvarial bone defect in mice. Then, the efficacy of cryopreserved hAM associated with a bone substitute was compared to a collagen membrane currently used for GBR. In vitro, no statistical difference was observed between the conditions concerning cell viability. Without graft material, cryopreserved hAM induced more bone formation when the mesenchymal layer covered the defect compared to the defect left empty. When associated with a bone substitute, such improved bone repair was not observed. These preliminary results suggest that cryopreserved hAM has a limited potential for GBR.

A Role for CD154, the CD40 Ligand, in Granulomatous Inflammation.

Granulomatous inflammation is a distinctive form of chronic inflammation in which predominant cells include macrophages, epithelioid cells, and multinucleated giant cells. Mechanisms regulating granulomatous inflammation remain ill-understood. CD154, the ligand of CD40, is a key mediator of inflammation. CD154 confers a proinflammatory phenotype to macrophages and controls several macrophagic functions. Here, we studied the contribution of CD154 in a mouse model of toxic liver injury with carbon tetrachloride and a model of absorbable suture graft. In both models, granulomas are triggered in response to endogenous persistent liver calcified necrotic lesions or by grafted sutures. CD154-deficient mice showed delayed clearance of carbon tetrachloride-induced liver calcified necrotic lesions and impaired progression of suture-induced granuloma. In vitro, CD154 stimulated phagocytosis of opsonized erythrocytes by macrophages, suggesting a potential mechanism for the altered granulomatous inflammation in CD154KO mice. These results suggest that CD154 may contribute to the natural history of granulomatous inflammation.

Layer-by-layer bioassembly of cellularized polylactic acid porous membranes for bone tissue engineering.

The conventional tissue engineering is based on seeding of macroporous scaffold on its surface ("top-down" approach). The main limitation is poor cell viability in the middle of the scaffold due to poor diffusion of oxygen and nutrients and insufficient vascularization. Layer-by-Layer (LBL) bioassembly is based on "bottom-up" approach, which considers assembly of small cellularized blocks. The aim of this work was to evaluate proliferation and differentiation of human bone marrow stromal cells (HBMSCs) and endothelial progenitor cells (EPCs) in two and three dimensions (2D, 3D) using a LBL assembly of polylactic acid (PLA) scaffolds fabricated by 3D printing. 2D experiments have shown maintain of cell viability on PLA, especially when a co-cuture system was used, as well as adequate morphology of seeded cells. Early osteoblastic and endothelial differentiations were observed and cell proliferation was increased after 7 days of culture. In 3D, cell migration was observed between layers of LBL constructs, as well as an osteoblastic differentiation. These results indicate that LBL assembly of PLA layers could be suitable for BTE, in order to promote homogenous cell distribution inside the scaffold and gene expression specific to the cells implanted in the case of co-culture system.

Web-Based Information on the Treatment of Tobacco Dependence for Oral Health Professionals: Analysis of English-Written Websites.

BACKGROUND: Studies have been conducted on the content and quality of Web-based information for patients who are interested in smoking cessation advice and for health care practitioners regarding the content of e-learning programs about tobacco cessation. However, to the best of our knowledge, there is no such information about the quality of Web-based learning resources regarding smoking cessation dedicated to oral health professionals. OBJECTIVE: The aim of this study was to identify and evaluate the quality of the content of webpages providing information about smoking cessation for oral health care professionals. METHODS: Websites were identified using Google and Health on Net (HON) search engines using the terms: smoking cessation OR quit smoking OR stop smoking OR 3As OR 5As OR tobacco counselling AND dentistry OR dental clinic OR dentist OR dental hygienist OR oral health professionals. The first 100 consecutive results of the 2 search engines were considered for the study. Quality assessment was rated using the DISCERN questionnaire, the Journal of the American Medical Association (JAMA) benchmarks, and the HON seal. In addition, smoking cessation content on each site was assessed using an abbreviated version of the Smoke Treatment Scale (STS-C) and the Smoking Treatment Scale-Rating (STS-R). To assess legibility of the selected websites, the Flesch Reading Ease (FRES) and the Flesch-Kinkaid Reading Grade Level (FKRGL) were used. Websites were also classified into multimedia and nonmultimedia and friendly and nonfriendly usability. RESULTS: Of the first 200 sites selected (100 of Google and 100 of HON), only 11 met the inclusion criteria and mainly belonged to governmental institutions (n=8), with the others being prepared by Professional Associations (n=2) and nonprofit organizations (n=1). Only 3 were exclusively dedicated to smoking cessation. The average score obtained with the DISCERN was 3.0, and the average score in the FKRGL and FRES was 13.31 (standard deviation, SD 3.34) and 40.73 (SD 15.46), respectively. Of the 11 websites evaluated, none achieved all the four JAMA benchmarks. The mean score of STS-R among all the websites was 2.81 (SD 0.95) out of 5. A significant strong positive correlation was obtained between the DISCERN mean values and the STS-R (R=.89, P=.01). CONCLUSIONS: The mean quality of webpages with information for oral health care professionals about smoking cessation is low and displayed a high heterogeneity. These webpages are also difficult to read and often lack multimedia resources, which further limits their usefulness.

[Oral cavity cancer: A distinct entity]. / Le cancer de la cavité orale : une entité spécifique ?

Oral Squamous cell carcinoma represent the 17th most frequent cancer in the world. The main risk factors are alcohol and tobacco consumption but dietary, familial, genetic, or oral diseases may be involved in oral carcinogenesis. Diagnosis is made on biopsy, but detection remains late, leading to a poor prognosis. New technologies could reduce these delays, notably Artificial Intelligence and the quantitative evaluation of salivary biological markers. Currently, management of oral cancer consists in surgery, which can be mutilating despite possible reconstructions. In the future, immunotherapies could become a therapeutic alternative and the immune microenvironment could constitute a source of prognostic markers.

Title: Le cancer de la cavité orale : une entité spécifique ? Abstract: Les carcinomes épidermoïdes de la cavité orale sont le 17e cancer le plus fréquent dans le monde. Les facteurs de risque principaux sont l'alcool et le tabac mais des facteurs alimentaires, familiaux, génétiques ou certaines maladies orales peuvent intervenir dans la genèse de ces cancers. Le diagnostic est tardif, entraînant un pronostic sombre. De nouvelles approches, comme l'utilisation de l'intelligence artificielle ou de marqueurs biologiques salivaires pourraient réduire ces délais. La prise en charge actuelle de ces cancers repose sur la chirurgie, la chimiothérapie et la radiothérapie, mais avec une iatrogénie importante. Les immunothérapies pourraient devenir une alternative à ces traitements et certaines caractéristiques du microenvironnement immunitaire pourraient constituer un/des marqueurs pronostiques.

[Uses of 3D printing and Bioprinting for pre-implant bone reconstruction in Oral Surgery]. / Impression 3D et bioimpression pour la régénération osseuse en chirurgie orale.

Pre-implant bone surgery in oral surgery allows to reconstruct maxillary atrophies related to traumatic, infectious or tumoral processes. In this context, the ideal biomaterial remains autogenous bone, but biomaterials (of natural or synthetic origin) allow to limit the morbidity linked to bone harvesting, and to simplify these surgical procedures. In this article, we illustrate how 3D printing technologies can be used as an adjuvant to treat bone defects of complex shape or to create anatomical models used to plan interventions. Finally, some perspectives brought by tissue engineering and bioprinting (creation of complex in vitro models) are presented.

Title: Impression 3D et bioimpression pour la régénération osseuse en chirurgie orale. Abstract: La chirurgie osseuse pré-implantaire en chirurgie orale permet de reconstruire les atrophies des maxillaires en rapport avec des processus traumatiques, infectieux ou tumoraux. Dans ce contexte, le biomatériau idéal reste l'os autogène mais les biomatériaux (d'origine naturelle ou synthétique) permettent de limiter la morbidité liée aux prélèvements osseux et de simplifier ces interventions chirurgicales. Dans cet article, nous illustrons l'apport récent de l'impression 3D dans ce contexte pour traiter des défauts osseux de forme complexe ou pour créer des modèles anatomiques servant à planifier les interventions. Enfin, les perspectives apportées par l'ingénierie tissulaire et la bioimpression (création de modèles in vitro complexes) sont détaillées.

Harnessing Human Placental Membrane-Derived Bioinks: Characterization and Applications in Bioprinting and Vasculogenesis.

Bioprinting applications in the clinical field generate great interest, but developing suitable biomaterial inks for medical settings is a challenge. Placental tissues offer a promising solution due to their abundance, stability, and status as medical waste. They contain basement membrane components, have a clinical history, and support angiogenesis. This study formulates bioinks from two placental tissues, amnion (AM) and chorion (CHO), and compares their unique extracellular matrix (ECM) and growth factor compositions. Rheological properties of the bioinks are evaluated for bioprinting and maturation of human endothelial cells. Both AM and Cho-derived bioinks sustained human endothelial cell viability, proliferation, and maturation, promoting optimal vasculogenesis. These bioinks derived from human sources have significant potential for tissue engineering applications, particularly in supporting vasculogenesis. This research contributes to the advancement of tissue engineering and regenerative medicine, bringing everyone closer to clinically viable bioprinting solutions using placental tissues as valuable biomaterials.

3D bioprinted breast cancer model reveals stroma-mediated modulation of extracellular matrix and radiosensitivity.

Deciphering breast cancer treatment resistance remains hindered by the lack of models that can successfully capture the four-dimensional dynamics of the tumor microenvironment. Here, we show that microextrusion bioprinting can reproducibly generate distinct cancer and stromal compartments integrating cells relevant to human pathology. Our findings unveil the functional maturation of this millimeter-sized model, showcasing the development of a hypoxic cancer core and an increased surface proliferation. Maturation was also driven by the presence of cancer-associated fibroblasts (CAF) that induced elevated microvascular-like structures complexity. Such modulation was concomitant to extracellular matrix remodeling, with high levels of collagen and matricellular proteins deposition by CAF, simultaneously increasing tumor stiffness and recapitulating breast cancer fibrotic development. Importantly, our bioprinted model faithfully reproduced response to treatment, further modulated by CAF. Notably, CAF played a protective role for cancer cells against radiotherapy, facilitating increased paracrine communications. This model holds promise as a platform to decipher interactions within the microenvironment and evaluate stroma-targeted drugs in a context relevant to human pathology.

Development of Novel Polysaccharide Membranes for Guided Bone Regeneration: In Vitro and In Vivo Evaluations.

INTRODUCTION: Guided bone regeneration (GBR) procedures require selecting suitable membranes for oral surgery. Pullulan and/or dextran-based polysaccharide materials have shown encouraging results in bone regeneration as bone substitutes but have not been used to produce barrier membranes. The present study aimed to develop and characterize pullulan/dextran-derived membranes for GBR. MATERIALS AND METHODS: Two pullulan/dextran-based membranes, containing or not hydroxyapatite (HA) particles, were developed. In vitro, cytotoxicity evaluation was performed using human bone marrow mesenchymal stem cells (hBMSCs). Biocompatibility was assessed on rats in a subcutaneous model for up to 16 weeks. In vivo, rat femoral defects were created on 36 rats to compare the two pullulan/dextran-based membranes with a commercial collagen membrane (Bio-Gide®). Bone repair was assessed radiologically and histologically. RESULTS: Both polysaccharide membranes demonstrated cytocompatibility and biocompatibility. Micro-computed tomography (micro-CT) analyses at two weeks revealed that the HA-containing membrane promoted a significant increase in bone formation compared to Bio-Gide®. At one month, similar effects were observed among the three membranes in terms of bone regeneration. CONCLUSION: The developed pullulan/dextran-based membranes evidenced biocompatibility without interfering with bone regeneration and maturation. The HA-containing membrane, which facilitated early bone regeneration and offered adequate mechanical support, showed promising potential for GBR procedures.

"Plasma cell gingivitis" encompasses multiple entities: a retrospective series of 37 cases.

BACKGROUND: Plasma cell gingivitis is defined as gingival inflammation comprised of plasma cell infiltrates. This diagnostic criterion is non-specific and underlying mechanisms remain unknown. OBJECTIVES: We performed a multidisciplinary clinico-pathological review of cases previously identified as "gingivitis with plasma cell infiltrates", with assessment of putative contributing factors and critical appraisal of the final diagnosis. MATERIALS & METHODS: Cases previously identified as "gingivitis with plasma cell infiltrates" between 2000 and 2020 were included from archives from the GEMUB group, a French multidisciplinary network of physicians with expertise on oral mucosa. RESULTS: Among the 37 included cases, multidisciplinary clinico-pathological review allowed differential diagnosis in seven cases (oral lichen planus n=4, plasma cell granuloma n=1, plasmacytoma n=1, and mucous membrane pemphigoid n=1). The remaining cases were classified as "reactive plasma cell gingivitis" (induced by drugs, trauma/irritation or periodontal disease) (n=18) or "idiopathic plasma cell gingivitis" when no contributing factors were identified (n=12). Clinico-pathological characteristics did not differ significantly between "reactive" and "idiopathic" cases, preventing us from identifying specific features of "idiopathic" plasma cell gingivitis. CONCLUSION: "Plasma cell gingivitis" is a polymorphous, non-specific entity with various aetiologies, of which the diagnosis requires multidisciplinary anatomo-clinical correlation for exclusion of secondary causes of plasma cell infiltration. Although our study was limited by its retrospective design, most cases of "plasma cell gingivitis" appeared to be associated with an underlying cause. We propose a diagnostic algorithm to properly investigate such cases.

Recent Advances of Pullulan and/or Dextran-Based Materials for Bone Tissue Engineering Strategies in Preclinical Studies: A Systematic Review.

Bone tissue engineering (BTE) strategies are increasingly investigated to overcome the limitations of currently used bone substitutes and to improve the bone regeneration process. Among the natural polymers used for tissue engineering, dextran and pullulan appear as natural hydrophilic polysaccharides that became promising biomaterials for BTE. This systematic review aimed to present the different published applications of pullulan and dextran-based biomaterials for BTE. An electronic search in Pubmed, Scopus, and Web of Science databases was conducted. Selection of articles was performed following PRISMA guidelines. This systematic review led to the inclusion of 28 articles on the use of pullulan and/or dextran-based biomaterials to promote bone regeneration in preclinical models. Sixteen studies focused on dextran-based materials for bone regeneration, six on pullulan substitutes and six on the combination of pullulan and dextran. Several strategies have been developed to provide bone regeneration capacity, mainly through their fabrication processes (functionalization methods, cross-linking process), or the addition of bioactive elements. We have summarized here the strategies employed to use the polysaccharide scaffolds (fabrication process, composition, application usages, route of administration), and we highlighted their relevance and limitations for BTE applications.

From local to global matrix organization by fibroblasts: a 4D laser-assisted bioprinting approach.

Fibroblasts and myofibroblasts play a central role in skin homeostasis through dermal organization and maintenance. Nonetheless, the dynamic interactions between (myo)fibroblasts and the extracellular matrix (ECM) remain poorly exploited in skin repair strategies. Indeed, there is still an unmet need for soft tissue models allowing to study the spatial-temporal remodeling properties of (myo)fibroblasts.In vivo, wound healing studies in animals are limited by species specificity.In vitro, most models rely on collagen gels reorganized by randomly distributed fibroblasts. But biofabrication technologies have significantly evolved over the past ten years. High-resolution bioprinting now allows to investigate various cellular micropatterns and the emergent tissue organizations over time. In order to harness the full dynamic properties of cells and active biomaterials, it is essential to consider 'time' as the 4th dimension in soft tissue design. Following this 4D bioprinting approach, we aimed to develop a novel model that could replicate fibroblast dynamic remodelingin vitro. For this purpose, (myo)fibroblasts were patterned on collagen gels with laser-assisted bioprinting (LAB) to study the generated matrix deformations and reorganizations. First, distinct populations, mainly composed of fibroblasts or myofibroblasts, were establishedin vitroto account for the variety of fibroblastic remodeling properties. Then, LAB was used to organize both populations on collagen gels in even isotropic patterns with high resolution, high density and high viability. With maturation, bioprinted patterns of fibroblasts and myofibroblasts reorganized into dispersed or aggregated cells, respectively. Stress-release contraction assays revealed that these phenotype-specific pattern maturations were associated with distinct lattice tension states. The two populations were then patterned in anisotropic rows in order to direct the cell-generated deformations and to orient global matrix remodeling. Only maturation of anisotropic fibroblast patterns, but not myofibroblasts, resulted in collagen anisotropic reorganizations both at tissue-scale, with lattice contraction, and at microscale, with embedded microbead displacements. Following a 4D bioprinting approach, LAB patterning enabled to elicit and orient the dynamic matrix remodeling mechanisms of distinct fibroblastic populations and organizations on collagen. For future studies, this method provides a new versatile tool to investigatein vitrodermal organizations and properties, processes of remodeling in healing, and new treatment opportunities.

Development of a vascular substitute produced by weaving yarn made from human amniotic membrane.

Because synthetic vascular prostheses perform poorly in small-diameter revascularization, biological vascular substitutes are being developed as an alternative. Although theirin vivoresults are promising, their production involves long, complex, and expensive tissue engineering methods. To overcome these limitations, we propose an innovative approach that combines the human amniotic membrane (HAM), which is a widely available and cost-effective biological raw material, with a rapid and robust textile-inspired assembly strategy. Fetal membranes were collected after cesarean deliveries at term. Once isolated by dissection, HAM sheets were cut into ribbons that could be further processed by twisting into threads. Characterization of the HAM yarns (both ribbons and threads) showed that their physical and mechanical properties could be easily tuned. Since our clinical strategy will be to provide an off-the-shelf allogeneic implant, we studied the effects of decellularization and/or gamma sterilization on the histological, mechanical, and biological properties of HAM ribbons. Gamma irradiation of hydrated HAMs, with or without decellularization, did not interfere with the ability of the matrix to support endothelium formationin vitro. Finally, our HAM-based, woven tissue-engineered vascular grafts (TEVGs) exhibited clinically relevant mechanical properties. Thus, this study demonstrates that human, completely biological, allogeneic, small-diameter TEVGs can be produced from HAM, thereby avoiding costly cell culture and bioreactors.