The effect of modifying the nanostructure of gelatin fiber scaffolds on early angiogenesis in vitro and in vivo

Two Factors ◽

Fiber Scaffolds

Abstract Early angiogenesis is one of the key challenges in tissue regeneration. Crosslinking mode and fiber diameter are critical factors to affect the adhesion and proliferation of cells. However, whether and how these two factors affect early angiogenesis remain largely unknown. To address the issue, the optimal crosslinking mode and fiber diameter of gelatin fiber membrane for early angiogenesis in vivo and in vitro were explored in this work. Compared with the post crosslinked gelatin fiber membrane with the same fiber diameter, the 700 nm diameter in situ crosslinked gelatin fiber membrane was found to have smaller roughness (230.67 ± 19 nm) and stronger hydrophilicity (54.77 ± 1.2°), which were suitable for cell growth and adhesion. Moreover, the in situ crosslinked gelatin fiber membrane with a fiber diameter of 1000 nm had significant advantages in early angiogenesis over the two with fiber diameters of 500 and 700 nm by up-regulating the expression of Ang1, VEGF, and integrin-β1. Our findings indicated that the in situ crosslinked gelatin fiber membrane with a diameter of 1000 nm might solve the problem of insufficient blood supply in the early stage of soft tissue regeneration and has broad clinical application prospects in promoting tissue regeneration.

An Investigation of Radial Reflux in an Isolated Peripheral Canine Vein Segment

Phlebology The Journal of Venous Disease ◽

10.1177/026835559501000308 ◽

1995 ◽

Vol 10 (3) ◽

pp. 115-121 ◽

Cited By ~ 6

Author(s):

T. P. Crotty

Keyword(s):

Turbulent Flow ◽

Varicose Veins ◽

Early Stage ◽

Vein Segment ◽

Adrenergic Activity ◽

Conventional Histology ◽

University Department

Objective: To investigate the effects of flow from the vein lumen into the vasa venarum (radial reflux) and the factors regulating it. Design: In vivo and in vitro animal study. Setting: University Department of Physiology. Materials: Segments of canine vein were perfused in vitro ( n = 84) and in situ ( n = 60). Main outcome measures: Specimens were studied by conventional histology using light microscopy. Results: Radial reflux caused dilatation of constricted segments and when associated with turbulent flow resulted in the formation of acute short-lived varices, marked dilatation of sinusoidal venules at the medioadventitial junction of the segments and of sinusoidal venules in the paradventitial tissue. Conclusion: During laminar flow radial reflux operated as a feedback to regulate venoconstrictor tone. During turbulent flow it caused more widespread vascular changes and inhibited adrenergic activity. The changes are of particular interest because they mimicked those that characterize the early stage of varicose veins.

In-Vivo Toxicity Studies and In-Vitro Inactivation of SARS-CoV-2 by Povidone-iodine In-situ Gel Forming Formulations

10.1101/2020.05.18.103184 ◽

2020 ◽

Cited By ~ 2

Author(s):

Bo Liang ◽

Xudong Yuan ◽

Gang Wei ◽

Wei Wang ◽

Ming Zhang ◽

...

Keyword(s):

Povidone Iodine ◽

Early Stage ◽

Etiologic Agent ◽

Dependent Manner ◽

Forming Technology ◽

Long Acting ◽

Dose Dependent

AbstractTo curb the spread of SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, we characterize the virucidal activity of long-acting Povidone Iodine (PVP-I) compositions developed using an in-situ gel forming technology. The PVP-I gel forming nasal spray (IVIEW-1503) and PVP-I gel forming ophthalmic eye drop (IVIEW-1201) rapidly inactivated SARS-CoV-2, inhibiting the viral infection of VERO76 cells. No toxicity was observed for the PVP-I formulations. Significant inactivation was noted with preincubation of the virus with these PVP-I formulations at the lowest concentrations tested. It has been demonstrated that both PVP-I formulations can inactivate SARS-CoV-2 virus efficiently in both a dose-dependent and a time-dependent manner. These results suggest IVIEW-1503 and IVIEW-1201 could be potential agents to reduce or prevent the transmission of the virus through the nasal cavity and the eye, respectively. Further studies are needed to clinically evaluate these formulations in early-stage COVID-19 patients.

Which substances loaded onto collagen scaffolds influence oral tissue regeneration?—an overview of the last 15 years

Clinical Oral Investigations ◽

10.1007/s00784-020-03520-0 ◽

2020 ◽

Vol 24 (10) ◽

pp. 3363-3394

Author(s):

Michael Edelmayer ◽

Christian Wehner ◽

Christian Ulm ◽

Werner Zechner ◽

David Shafer ◽

...

Keyword(s):

Tissue Regeneration ◽

Release Kinetics ◽

Tissue Cell ◽

Collagen Scaffolds ◽

Positive Effects ◽

Oral Tissue ◽

Periodontal Healing

Abstract Background Collagen scaffolds are widely used for guided bone or tissue regeneration. Aiming to enhance their regenerative properties, studies have loaded various substances onto these scaffolds. This review aims to provide an overview of existing literature which conducted in vitro, in vivo, and clinical testing of drug-loaded collagen scaffolds and analyze their outcome of promoting oral regeneration. Materials and methods PubMed, Scopus, and Ovid Medline® were systematically searched for publications from 2005 to 2019. Journal articles assessing the effect of substances on oral hard or soft tissue regeneration, while using collagen carriers, were screened and qualitatively analyzed. Studies were grouped according to their used substance type—biological medical products, pharmaceuticals, and tissue-, cell-, and matrix-derived products. Results A total of 77 publications, applying 36 different substances, were included. Collagen scaffolds were demonstrating favorable adsorption behavior and release kinetics which could even be modified. BMP-2 was investigated most frequently, showing positive effects on oral tissue regeneration. BMP-9 showed comparable results at lower concentrations. Also, FGF2 enhanced bone and periodontal healing. Antibiotics improved the scaffold’s anti-microbial activity and reduced the penetrability for bacteria. Conclusion Growth factors showed promising results for oral tissue regeneration, while other substances were investigated less frequently. Found effects of investigated substances as well as adsorption and release properties of collagen scaffolds should be considered for further investigation. Clinical relevance: Collagen scaffolds are reliable carriers for any of the applied substances. BMP-2, BMP-9, and FGF2 showed enhanced bone and periodontal healing. Antibiotics improved anti-microbial properties of the scaffolds.

Exosomes derived from stem cells from apical papilla promote craniofacial soft tissue regeneration by enhancing Cdc42-mediated vascularization

10.21203/rs.3.rs-60880/v3 ◽

2021 ◽

Author(s):

Yao Liu ◽

Xueying Zhuang ◽

Si Yu ◽

Ning Yang ◽

Jianhong Zeng ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Cell Migration ◽

Soft Tissue ◽

Tissue Regeneration ◽

Apical Papilla ◽

Abstract Background: Reconstruction of complex critical-size defects (CSD) in the craniofacial region is a major challenge, and soft tissue regeneration is crucial in determining the therapeutic outcomes of craniofacial CSD. Stem cells from apical papilla (SCAP) are neural crest-derived mesenchymal stem cells (MSCs) that are homologous to cells in craniofacial tissue and represent a promising source for craniofacial tissue regeneration. Exosomes, which contain compound bioactive compounds, are the key factors in stem cell paracrine action. However, the roles of exosomes derived from SCAP (SCAP-Exo) in tissue regeneration are not fully understood. Here, we explored the effects and underlying mechanisms of SCAP-Exo on CSD in maxillofacial soft tissue. Methods: SCAP-Exo were isolated and identified by transmission electron microscopy and nanoparticle tracking analysis. The effects of SCAP-Exo on wound healing and vascularization were detected by measuring the wound area and performing histological and immunofluorescence analysis on the palatal gingival CSD of mice. Real-time live cell imaging and functional assays were used to assess the effects of SCAP-Exo on the biological functions of endothelial cells (ECs). Furthermore, the molecular mechanisms of SCAP-Exo-mediated EC angiogenesis in vitro were tested by immunofluorescence staining, Western blot and pull-down assays. Finally, in vivo experiments were carried out to verify whether SCAP-Exo could affect vascularization and wound healing through cell division cycle 42 (Cdc42). Results: We found that SCAP-Exo promoted tissue regeneration of palatal gingival CSD by enhancing vascularization in the early phase in vivo and that SCAP-Exo improved the angiogenic capacity of ECs in vitro . Mechanistically, SCAP-Exo elevated cell migration by improving cytoskeletal reorganization of ECs via Cdc42 signalling. Furthermore, we revealed that SCAP-Exo transferred Cdc42 into the cytoplasm of ECs and that the Cdc42 protein could be reused directly by recipient ECs, which resulted in the activation of Cdc42-dependent filopodium formation and elevation in cell migration of ECs. Conclusion: This study demonstrated that SCAP-Exo had a superior effect on angiogenesis and effectively promoted craniofacial soft tissue regeneration. These data provide a new option for SCAP-Exo to be used in a cell-free approach to optimize tissue regeneration in the clinic.

Macrophage Identification In Situ

Biomedicines ◽

10.3390/biomedicines9101393 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1393

Author(s):

Krisztina Nikovics ◽

Anne-Laure Favier

Keyword(s):

Tissue Regeneration ◽

Reporter Genes ◽

Cellular Mechanisms ◽

Comprehensive Overview ◽

Distinctive Features ◽

Long Time

Understanding the processes of inflammation and tissue regeneration after injury is of great importance. For a long time, macrophages have been known to play a central role during different stages of inflammation and tissue regeneration. However, the molecular and cellular mechanisms by which they exert their effects are as yet mostly unknown. While in vitro macrophages have been characterized, recent progress in macrophage biology studies revealed that macrophages in vivo exhibited distinctive features. Actually, the precise characterization of the macrophages in vivo is essential to develop new healing treatments and can be approached via in situ analyses. Nowadays, the characterization of macrophages in situ has improved significantly using antigen surface markers and cytokine secretion identification resulting in specific patterns. This review aims for a comprehensive overview of different tools used for in situ macrophage identification, reporter genes, immunolabeling and in situ hybridization, discussing their advantages and limitations.

Exosomes Derived From Stem Cells From Apical Papilla Promote Craniofacial Soft Tissue Regeneration Through Enhancing Cdc42-Mediated Vascularization

10.21203/rs.3.rs-60880/v1 ◽

2020 ◽

Author(s):

Yao Liu ◽

Xueying Zhuang ◽

Si Yu ◽

Ning Yang ◽

Jianhong Zeng ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Endothelial Cells ◽

Soft Tissue ◽

Tissue Regeneration ◽

Apical Papilla ◽

Abstract Background: Reconstruction of complex critical-size defects (CSD) in craniofacial region is a major challenge, and the soft tissue regeneration is crucial in determining the therapeutic outcome of craniofacial CSD. Stem cells from apical papilla (SCAP) are neural crest-derived mesenchymal stem cells (MSCs) which are homologous to craniofacial tissue, and represent a promising source for craniofacial tissue regeneration. Exosomes, which contained compound bioactive contents, are the key factors of stem cell paracrine action. However, the roles of exosomes derived from SCAP (SCAP-Exo) in tissue regeneration are not fully understood. Here, we explored the effects and underlying mechanisms of SCAP-Exo on CSD in maxillofacial soft tissue.Methods: SCAP-Exo were isolated and identified by transmission electron microscopy and nanoparticle tracking analysis. The effects of SCAP-Exo on wound healing and vascularisation were detected by measuring wound area, histological and immunofluorescence analysis in the palate gingiva CSD of mice. Real-time live cell imaging and functional assays were used to assess the effects of SCAP-Exo on the biological functions of endothelial cells (ECs). Furthermore, the molecular mechanisms of SCAP-Exo mediated ECs angiogenesis in vitro was tested by immunofluorescence staining, Western blot and Pull-Down assays. Finally, in vivo experiments were carried out to verify whether SCAP-Exo could affect the vascularisation and wound healing through Cdc42.Results: We showed that SCAP-Exo promoted tissue regeneration of palatal gingiva CSD by enhancing vascularisation in the early phase in vivo, and also indicated SCAP-Exo improved the angiogenic capacity of endothelial cells (ECs) in vitro. Mechanistically, SCAP-Exo elevated cell migration by improving cytoskeletal reorganization of ECs via cell division cycle 42 (Cdc42) signalling. Furthermore, we revealed that SCAP-Exo transferred Cdc42 into the cytoplasm of ECs, and the Cdc42 protein could be reused directly by the recipient ECs, which resulted in the activation of Cdc42 dependent filopodia formation and elevation of cell migration of ECs.Conclusion: This study demonstrated that SCAP-Exo had a superior effect on angiogenesis and effectively promoted craniofacial soft tissue regeneration. These data provide a new option for SCAP-Exo to be used as a cell-free approach to optimize tissue regeneration in the clinic.

Multiblock copolymers type PDC- a family of multifunctional biomaterials for regenerative medicine1

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-211264 ◽

2021 ◽

pp. 1-15

Author(s):

Imram Ullah ◽

Weiwei Wang ◽

Nan Ma ◽

Andreas Lendlein

Keyword(s):

Tissue Regeneration ◽

Initial Phase ◽

Shape Memory Polymers ◽

Multiblock Copolymers ◽

Promising Candidate ◽

Structural Support ◽

Cell Material Interactions

Multiblock copolymers type PDC are polyetheresterurethanes composed of poly(ɛ-caprolactone) and poly(p-dioxanone) segments. They were designed as degradadable shape-memory polymers for medical devices, which can be implanted minimally-invasively. While providing structural support in the initial phase after implantation, they are capable to modulate soft tissue regeneration while degradation. In this perspective, we elucidate cell-material interactions, compatibility both in-vitro and in-vivo and biofunctionality of PDC, which represents a promising candidate biomaterial family especially for cardiovascular applications.

The Selective Centrifugation Ensures a Better In Vitro Isolation of ASCs and Restores a Soft Tissue Regeneration In Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms18051038 ◽

2017 ◽

Vol 18 (5) ◽

pp. 1038 ◽

Cited By ~ 6

Author(s):

Francesco De Francesco ◽

Antonio Guastafierro ◽

Gianfranco Nicoletti ◽

Sergio Razzano ◽

Michele Riccio ◽

...

Keyword(s):

Soft Tissue ◽

Tissue Regeneration ◽

Soft Tissue Regeneration

Exosomes derived from stem cells from apical papilla promote craniofacial soft tissue regeneration by enhancing Cdc42-mediated vascularization

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02151-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yao Liu ◽

Xueying Zhuang ◽

Si Yu ◽

Ning Yang ◽

Jianhong Zeng ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Cell Migration ◽

Soft Tissue ◽

Tissue Regeneration ◽

Apical Papilla ◽

Abstract Background Reconstruction of complex critical-size defects (CSD) in the craniofacial region is a major challenge, and soft tissue regeneration is crucial in determining the therapeutic outcomes of craniofacial CSD. Stem cells from apical papilla (SCAP) are neural crest-derived mesenchymal stem cells (MSCs) that are homologous to cells in craniofacial tissue and represent a promising source for craniofacial tissue regeneration. Exosomes, which contain compound bioactive compounds, are the key factors in stem cell paracrine action. However, the roles of exosomes derived from SCAP (SCAP-Exo) in tissue regeneration are not fully understood. Here, we explored the effects and underlying mechanisms of SCAP-Exo on CSD in maxillofacial soft tissue. Methods SCAP-Exo were isolated and identified by transmission electron microscopy and nanoparticle tracking analysis. The effects of SCAP-Exo on wound healing and vascularization were detected by measuring the wound area and performing histological and immunofluorescence analysis on the palatal gingival CSD of mice. Real-time live-cell imaging and functional assays were used to assess the effects of SCAP-Exo on the biological functions of endothelial cells (ECs). Furthermore, the molecular mechanisms of SCAP-Exo-mediated EC angiogenesis in vitro were tested by immunofluorescence staining, Western blot, and pull-down assays. Finally, in vivo experiments were carried out to verify whether SCAP-Exo could affect vascularization and wound healing through cell division cycle 42 (Cdc42). Results We found that SCAP-Exo promoted tissue regeneration of palatal gingival CSD by enhancing vascularization in the early phase in vivo and that SCAP-Exo improved the angiogenic capacity of ECs in vitro. Mechanistically, SCAP-Exo elevated cell migration by improving cytoskeletal reorganization of ECs via Cdc42 signalling. Furthermore, we revealed that SCAP-Exo transferred Cdc42 into the cytoplasm of ECs and that the Cdc42 protein could be reused directly by recipient ECs, which resulted in the activation of Cdc42-dependent filopodium formation and elevation in cell migration of ECs. Conclusion This study demonstrated that SCAP-Exo had a superior effect on angiogenesis and effectively promoted craniofacial soft tissue regeneration. These data provide a new option for SCAP-Exo to be used in a cell-free approach to optimize tissue regeneration in the clinic.

Exosomes derived from stem cells from apical papilla promote craniofacial soft tissue regeneration through enhancing Cdc42-mediated vascularization

10.21203/rs.3.rs-60880/v2 ◽

2020 ◽

Author(s):

Yao Liu ◽

Xueying Zhuang ◽

Si Yu ◽

Ning Yang ◽

Jianhong Zeng ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Endothelial Cells ◽

Soft Tissue ◽

Tissue Regeneration ◽

Apical Papilla ◽

Abstract Background: Reconstruction of complex critical-size defects (CSD) in craniofacial region is a major challenge, and the soft tissue regeneration is crucial in determining the therapeutic outcome of craniofacial CSD. Stem cells from apical papilla (SCAP) are neural crest-derived mesenchymal stem cells (MSCs) which are homologous to craniofacial tissue, and represent a promising source for craniofacial tissue regeneration. Exosomes, which contained compound bioactive contents, are the key factors of stem cell paracrine action. However, the roles of exosomes derived from SCAP (SCAP-Exo) in tissue regeneration are not fully understood. Here, we explored the effects and underlying mechanisms of SCAP-Exo on CSD in maxillofacial soft tissue. Methods: SCAP-Exo were isolated and identified by transmission electron microscopy and nanoparticle tracking analysis. The effects of SCAP-Exo on wound healing and vascularisation were detected by measuring wound area, histological and immunofluorescence analysis in the palate gingiva CSD of mice. Real-time live cell imaging and functional assays were used to assess the effects of SCAP-Exo on the biological functions of endothelial cells (ECs). Furthermore, the molecular mechanisms of SCAP-Exo mediated ECs angiogenesis in vitro was tested by immunofluorescence staining, Western blot and Pull-Down assays. Finally, in vivo experiments were carried out to verify whether SCAP-Exo could affect the vascularisation and wound healing through Cdc42. Results: We showed that SCAP-Exo promoted tissue regeneration of palatal gingiva CSD by enhancing vascularisation in the early phase in vivo , and also indicated SCAP-Exo improved the angiogenic capacity of endothelial cells (ECs) in vitro . Mechanistically, SCAP-Exo elevated cell migration by improving cytoskeletal reorganization of ECs via cell division cycle 42 (Cdc42) signalling. Furthermore, we revealed that SCAP-Exo transferred Cdc42 into the cytoplasm of ECs, and the Cdc42 protein could be reused directly by the recipient ECs, which resulted in the activation of Cdc42 dependent filopodia formation and elevation of cell migration of ECs. Conclusion: This study demonstrated that SCAP-Exo had a superior effect on angiogenesis and effectively promoted craniofacial soft tissue regeneration. These data provide a new option for SCAP-Exo to be used as a cell-free approach to optimize tissue regeneration in the clinic.