scholarly journals Engineered mucoperiosteal scaffold for cleft palate regeneration towards the non-immunogenic transplantation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. I. Rizzo ◽  
L. Tomao ◽  
S. Tedesco ◽  
M. Cajozzo ◽  
M. Esposito ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Host Cells ◽  
Mesenchymal Precursor Cells ◽  
Set Up ◽  
Palate Bone ◽  
Palatal Bone ◽  
Molecular Resonance

AbstractCleft lip and palate (CL/P) is the most prevalent craniofacial birth defect in humans. None of the surgical procedures currently used for CL/P repair lead to definitive correction of hard palate bone interruption. Advances in tissue engineering and regenerative medicine aim to develop new strategies to restore palatal bone interruption by using tissue or organ-decellularized bioscaffolds seeded with host cells. Aim of this study was to set up a new natural scaffold deriving from a decellularized porcine mucoperiosteum, engineered by an innovative micro-perforation procedure based on Quantum Molecular Resonance (QMR) and then subjected to in vitro recellularization with human bone marrow-derived mesenchymal stem cells (hBM-MSCs). Our results demonstrated the efficiency of decellularization treatment gaining a natural, non-immunogenic scaffold with preserved collagen microenvironment that displays a favorable support to hMSC engraftment, spreading and differentiation. Ultrastructural analysis showed that the micro-perforation procedure preserved the collagen mesh, increasing the osteoinductive potential for mesenchymal precursor cells. In conclusion, we developed a novel tissue engineering protocol to obtain a non-immunogenic mucoperiosteal scaffold suitable for allogenic transplantation and CL/P repair. The innovative micro-perforation procedure improving hMSC osteogenic differentiation potentially impacts for enhanced palatal bone regeneration leading to future clinical applications in humans.

scholarly journals Effective decellularisation of human saphenous veins for biocompatible arterial tissue engineering applications: Bench optimisation and feasibility in vivo testing

2021 ◽  
Vol 12 ◽  
pp. 204173142098752
Author(s):  
Nadiah S Sulaiman ◽  
Andrew R Bond ◽  
Vito D Bruno ◽  
John Joseph ◽  
Jason L Johnson ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Mechanical Strength ◽  
Vascular Tissue ◽  
Sodium Dodecyl ◽  
Host Cells ◽  
Replacement Model ◽  
In Vivo Testing ◽  
Vascular Scaffolds

Human saphenous vein (hSV) and synthetic grafts are commonly used conduits in vascular grafting, despite high failure rates. Decellularising hSVs (D-hSVs) to produce vascular scaffolds might be an effective alternative. We assessed the effectiveness of a detergent-based method using 0% to 1% sodium dodecyl sulphate (SDS) to decellularise hSV. Decellularisation effectiveness was measured in vitro by nuclear counting, DNA content, residual cell viability, extracellular matrix integrity and mechanical strength. Cytotoxicity was assessed on human and porcine cells. The most effective SDS concentration was used to prepare D-hSV grafts that underwent preliminary in vivo testing using a porcine carotid artery replacement model. Effective decellularisation was achieved with 0.01% SDS, and D-hSVs were biocompatible after seeding. In vivo xeno-transplantation confirmed excellent mechanical strength and biocompatibility with recruitment of host cells without mechanical failure, and a 50% patency rate at 4-weeks. We have developed a simple biocompatible methodology to effectively decellularise hSVs. This could enhance vascular tissue engineering toward future clinical applications.

scholarly journals SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Shiyu Chen ◽  
Zhonglin Jia ◽  
Ming Cai ◽  
Mujie Ye ◽  
Dandan Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Noncoding Rna ◽  
Chondrogenic Differentiation ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Tissue Sample ◽  
Human Umbilical Cord

Non-syndromic cleft lip and palate (NSCLP) is one of the most common congenital malformations with multifactorial etiology. Although long non-coding RNAs (lncRNAs) have been implicated in the development of lip and palate, their roles in NSCLP are not fully elucidated. This study aimed to investigate how dysregulated lncRNAs contribute to NSCLP. Using lncRNA sequencing, bioinformatics analysis, and clinical tissue sample detection, we identified that lncRNA ZFAS1 was significantly upregulated in NSCLP. The upregulation of ZFAS1 mediated by SP1 transcription factor (SP1) inhibited expression levels of Wnt family member 4 (WNT4) through the binding with CCCTC-binding factor (CTCF), subsequently inactivating the WNT/β-catenin signaling pathway, which has been reported to play a significant role on the development of lip and palate. Moreover, in vitro, the overexpression of ZFAS1 inhibited cell proliferation and migration in human oral keratinocytes and human umbilical cord mesenchymal stem cells (HUC-MSCs) and also repressed chondrogenic differentiation of HUC-MSCs. In vivo, ZFAS1 suppressed cell proliferation and numbers of chondrocyte in the zebrafish ethmoid plate. In summary, these results indicated that ZFAS1 may be involved in NSCLP by affecting cell proliferation, migration, and chondrogenic differentiation through inactivating the WNT/β-catenin signaling pathway.

Biallelic mutations in the TOGARAM1 gene cause a novel primary ciliopathy

2020 ◽  
pp. jmedgenet-2020-106833
Author(s):  
Valeria Morbidoni ◽  
Emanuele Agolini ◽  
Kevin C Slep ◽  
Luca Pannone ◽  
Daniela Zuccarello ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Developmental Disorders ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Missense Variant ◽  
Causative Role ◽  
Biallelic Mutations ◽  
The Impact

BackgroundDysfunction in non-motile cilia is associated with a broad spectrum of developmental disorders characterised by clinical heterogeneity. While over 100 genes have been associated with primary ciliopathies, with wide phenotypic overlap, some patients still lack a molecular diagnosis.ObjectiveTo investigate and functionally characterise the molecular cause of a malformation disorder observed in two sibling fetuses characterised by microphthalmia, cleft lip and palate, and brain anomalies.MethodsA trio-based whole exome sequencing (WES) strategy was used to identify candidate variants in the TOGARAM1 gene. In silico, in vitro and in vivo (Caenorhabditis elegans) studies were carried out to explore the impact of mutations on protein structure and function, and relevant biological processes.ResultsTOGARAM1 encodes a member of the Crescerin1 family of proteins regulating microtubule dynamics. Its orthologue in C. elegans, che-12, is expressed in a subset of sensory neurons and localises in the dendritic cilium where it is required for chemosensation. Nematode lines harbouring the corresponding missense variant in TOGARAM1 were generated by CRISPR/Cas9 technology. Although chemotaxis ability on a NaCl gradient was not affected, che-12 point mutants displayed impaired lipophilic dye uptake, with shorter and altered cilia in sensory neurons. Finally, in vitro analysis of microtubule polymerisation in the presence of wild-type or mutant TOG2 domain revealed a faster polymerisation associated with the mutant protein, suggesting aberrant tubulin binding.ConclusionsOur data are in favour of a causative role of TOGARAM1 variants in the pathogenesis of this novel disorder, connecting this gene with primary ciliopathy.

scholarly journals Smart Porous Multi-Stimulus Polysaccharide-Based Biomaterials for Tissue Engineering

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5286
Author(s):  
Fernando Alvarado-Hidalgo ◽  
Karla Ramírez-Sánchez ◽  
Ricardo Starbird-Perez
Keyword(s):  
Tissue Engineering ◽  
Porous Materials ◽  
In Vitro Regeneration ◽  
Textural Properties ◽  
Host Cells ◽  
Future Research ◽  
Porous Scaffolds ◽  
3D Scaffold ◽  
Stimulation Of

Recently, tissue engineering and regenerative medicine studies have evaluated smart biomaterials as implantable scaffolds and their interaction with cells for biomedical applications. Porous materials have been used in tissue engineering as synthetic extracellular matrices, promoting the attachment and migration of host cells to induce the in vitro regeneration of different tissues. Biomimetic 3D scaffold systems allow control over biophysical and biochemical cues, modulating the extracellular environment through mechanical, electrical, and biochemical stimulation of cells, driving their molecular reprogramming. In this review, first we outline the main advantages of using polysaccharides as raw materials for porous scaffolds, as well as the most common processing pathways to obtain the adequate textural properties, allowing the integration and attachment of cells. The second approach focuses on the tunable characteristics of the synthetic matrix, emphasizing the effect of their mechanical properties and the modification with conducting polymers in the cell response. The use and influence of polysaccharide-based porous materials as drug delivery systems for biochemical stimulation of cells is also described. Overall, engineered biomaterials are proposed as an effective strategy to improve in vitro tissue regeneration and future research directions of modified polysaccharide-based materials in the biomedical field are suggested.

scholarly journals ORAL AND CRANIOFACIAL CHARACTERISTICS OF UNTREATED ADULT UNILATERAL CLEFT LIP AND PALATE INDIVIDUALS

2012 ◽  
Vol 02 (03) ◽  
pp. 16-20
Author(s):  
M. S. Ravi
Keyword(s):  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Sagittal Plane ◽  
Dental Morphology ◽  
Facial Morphology ◽  
Lateral Cephalogram ◽  
The Common ◽  
Set Up ◽  
The Individual ◽  
Craniofacial Characteristics

Abstract Introduction: Cleft lip and palate anomaly being the common congenital defect having significant effects on the facial morphology, function and growth and development of the individual, requires a detailed study of the Dental and craniofacial characteristics. Design and setting: The study is conducted in a hospital set up and the subjects were selected at random as per the inclusion criterion. Objectiveof study was to evaluate the craniofacial and Dental morphology in untreated unilateral cleft lip and palate (UCLP) individuals. Materials and Methods: A total of 64 individuals in the age group of 15-28 yrs were selected and grouped in to two groups; Cleft group consisting of 13 males and 19 females having untreated UCLP and another group of 16 male and 16female non cleft individuals. Study cast, lateral cephalogram and frontal cephalogram analysis were carried out .The obtained data were analyzed using ANOVA to compare the values between the groups. Result: Significant differences in cranio- facial characteristics were noted between the cleft and non cleft individuals. These differences were more pronounced in sagittal plane and less in transverse plane. Conclusion: Significant differences exist in the cranio- facial morphology between the untreated UCLP individuals and non cleft individuals.

scholarly journals Biomaterials for Cleft Lip and Palate Regeneration

2019 ◽  
Vol 20 (9) ◽  
pp. 2176 ◽  
Author(s):  
Marcela Martín-del-Campo ◽  
Raúl Rosales-Ibañez ◽  
Luis Rojo
Keyword(s):  
Tissue Engineering ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Self Esteem ◽  
Cell Therapies ◽  
Face Area ◽  
Hard Tissues ◽  
Cleft Lip Palate ◽  
Advanced Biomaterials ◽  
Craniofacial Defect

Craniofacial bone defect anomalies affect both soft and hard tissues and can be caused by trauma, bone recessions from tumors and cysts, or even from congenital disorders. On this note, cleft/lip palate is the most prevalent congenital craniofacial defect caused by disturbed embryonic development of soft and hard tissues around the oral cavity and face area, resulting in most cases, of severe limitations with chewing, swallowing, and talking as well as problems of insufficient space for teeth, proper breathing, and self-esteem problems as a consequence of facial appearance. Spectacular advances in regenerative medicine have arrived, giving new hope to patients that can benefit from new tissue engineering therapies based on the supportive action of 3D biomaterials together with the synergic action of osteo-inductive molecules and recruited stem cells that can be driven to the process of bone regeneration. However, few studies have focused on the application of tissue engineering to the regeneration of the cleft/lip and only a few have reported significant advances to offer real clinical solutions. This review provides an updated and deep analysis of the studies that have reported on the use of advanced biomaterials and cell therapies for the regeneration of cleft lip and palate regeneration.

scholarly journals The biomechanical evaluation of magnetic forces to drive osteogenesis in newborn’s with cleft lip and palate

2020 ◽  
Vol 31 (9) ◽  
Author(s):  
Prasad Nalabothu ◽  
Carlalberta Verna ◽  
Markus Steineck ◽  
Andreas Albert Mueller ◽  
Michel Dalstra
Keyword(s):  
Cleft Lip ◽  
Load Transfer ◽  
Cleft Lip And Palate ◽  
Element Model ◽  
Bone Apposition ◽  
Magnetic Attraction ◽  
Distraction Device ◽  
Palatal Rugae ◽  
Biomechanical Evaluation ◽  
Set Up

Abstract This study examined the potential for dental magnets to act as a driving force for osteogenesis in the palate of newborns with a unilateral cleft lip and palate. In the first part of the study dental magnets were arranged in a set up mimicking a distraction device and the curves of the magnetic attraction force versus gap distance curves generated, with and without the presence of palatal rugae tissue in between both sides of the distraction device. The attraction forces ranged from 1 to 12 N depending on the gap distance and the presence of soft tissue in the gap. In the second part of the study these forces were used as input for a 3D finite element model of the palate of a newborn affected by unilateral cleft lip and palate. In the analysis of load transfer, it was found that the strains generated by a magnetically induced distraction exceed 1,500 µstrain suggesting that bone locally is submitted to mild overload leading to bone apposition.

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