Biological Mechanisms for Cartilage Repair Using a BioCartilage Scaffold: Cellular Adhesion/Migration and Bioactive Proteins

Cartilage ◽  
2020 ◽  
pp. 194760351990080 ◽  
Author(s):  
Jacqueline Commins ◽  
Rebecca Irwin ◽  
Andrea Matuska ◽  
Margaret Goodale ◽  
Michelle Delco ◽  
...  
Keyword(s):  
Fibrin Glue ◽  
Cartilage Repair ◽  
Matrix Protein ◽  
Cell Attachment ◽  
Interleukin 1 ◽  
Cellular Adhesion ◽  
Cellular Migration ◽  
Cartilage Explants ◽  
Cartilage Defects ◽  
Bioactive Proteins

Objective. BioCartilage is a desiccated, particulated cartilage allograft used for repair of focal cartilage defects. It is mixed with a biologic such as bone marrow concentrate (BMC), pressed into a contained defect, and sealed with fibrin glue. The objective of this study was to assess if BioCartilage could serve as a bioactive scaffold by affecting cellular adhesion, cellular migration, or the release interleukin-1 receptor antagonist protein (IL-1RA), and to identify its full proteomic makeup. Design. Cartilage explants were used to model confined defects. BioCartilage was mixed with BMC, grafted into defects, and sealed with 1 of 5 fibrin glues. Constructs were cultured for 24 or 48 hours and then processed for live/dead microscopy. Chondrocyte and mesenchymal stem cell (MSC) adhesion on BioCartilage was assessed using scanning electron microscopy. Conditioned medium from cultures and the biologics used in the study were assayed for IL-1RA. The protein footprint of BioCartilage was determined using bottom-up proteomics. Results. BioCartilage supported chondrocyte and MSC attachment within 24 hours, and cell viability was retained in all constructs at 24 and 48 hours. Fibrin glue did not inhibit cell attachment. BMC had the highest concentration of IL-1RA. Proteomics yielded 254 proteins, including collagens, proteoglycans, and several bioactive proteins with known anabolic roles including cartilage oligomeric matrix protein. Conclusions. This study suggests that BioCartilage has the chemical composition and architecture to support cell adherence and migration and to provide bioactive proteins, which together should have biologics advantages in cartilage repair beyond its role as a scaffold.

scholarly journals Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up

2021 ◽  
Vol 9 (1) ◽  
pp. 232596712097305
Author(s):  
Hong-Chul Lim ◽  
Yong-Beom Park ◽  
Chul-Won Ha ◽  
Brian J. Cole ◽  
Beom-Koo Lee ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Cartilage Repair ◽  
Older Patients ◽  
Cartilage Defects ◽  
Full Thickness ◽  
Phase 3 ◽  
Randomized Controlled ◽  
Cartilage Restoration

Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood–derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group ( P = .051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group ( P = .001); the overall histologic assessment score was also superior in the UCB-MSC-HA group ( P = .036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up ( P < .05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).

Fibrin glue does not improve the fixation of press-fitted cell-free collagen gel plugs in an ex vivo cartilage repair model

2011 ◽  
Vol 20 (2) ◽  
pp. 210-215 ◽  
Author(s):  
Turgay Efe ◽  
Alexander Füglein ◽  
Thomas J. Heyse ◽  
Thomas Stein ◽  
Nina Timmesfeld ◽  
...  
Keyword(s):  
Fibrin Glue ◽  
Cartilage Repair ◽  
Ex Vivo ◽  
Collagen Gel

scholarly journals Low-Intensity Pulsed Ultrasound Promotes Autophagy-Mediated Migration of Mesenchymal Stem Cells and Cartilage Repair

2021 ◽  
Vol 30 ◽  
pp. 096368972098614
Author(s):  
Peng Xia ◽  
Xinwei Wang ◽  
Qi Wang ◽  
Xiaoju Wang ◽  
Qiang Lin ◽  
...  
Keyword(s):  
Cartilage Repair ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Histopathological Analysis ◽  
Pulsed Ultrasound ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
Autophagy Inhibitor

Mesenchymal stem cell (MSC) migration is promoted by low-intensity pulsed ultrasound (LIPUS), but its mechanism is unclear. Since autophagy is known to regulate cell migration, our study aimed to investigate if LIPUS promotes the migration of MSCs via autophagy regulation. We also aimed to investigate the effects of intra-articular injection of MSCs following LIPUS stimulation on osteoarthritis (OA) cartilage. For the in vitro study, rat bone marrow-derived MSCs were treated with an autophagy inhibitor or agonist, and then they were stimulated by LIPUS. Migration of MSCs was detected by transwell migration assays, and stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR4) protein levels were quantified. For the in vivo study, a rat knee OA model was generated and treated with LIPUS after an intra-articular injection of MSCs with autophagy inhibitor added. The cartilage repair was assessed by histopathological analysis and extracellular matrix protein expression. The in vitro results suggest that LIPUS increased the expression of SDF-1 and CXCR4, and it promoted MSC migration. These effects were inhibited and enhanced by autophagy inhibitor and agonist, respectively. The in vivo results demonstrate that LIPUS significantly enhanced the cartilage repair effects of MSCs on OA, but these effects were blocked by autophagy inhibitor. Our results suggest that the migration of MSCs was enhanced by LIPUS through the activation autophagy, and LIPUS improved the protective effect of MSCs on OA cartilage via autophagy regulation.

scholarly journals Effects of a New Bioceramic Material on Human Apical Papilla Cells

2018 ◽  
Vol 9 (4) ◽  
pp. 74 ◽  
Author(s):  
Diana Sequeira ◽  
Catarina Seabra ◽  
Paulo Palma ◽  
Ana Cardoso ◽  
João Peça ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mineral Trioxide Aggregate ◽  
Cellular Adhesion ◽  
Cellular Migration ◽  
Cellular Viability ◽  
Migration Rates ◽  
Apical Papilla ◽  
And Migration ◽  
Proliferation And Migration

Background: The development of materials with bioregenerative properties is critically important for vital pulp therapies and regenerative endodontic procedures. The aim of this study was to evaluate the cytocompatibility and cytotoxicity of a new endodontic biomaterial, PulpGuard, in comparison with two other biomaterials widely used in endodontic procedures, ProRoot Mineral Trioxide Aggregate (MTA) and Biodentine. Methods: Apical papilla cells (APCs) were isolated from third molars with incomplete rhizogenesis from patients with orthodontic indication for dental extraction. Cultured APCs were incubated for 24, 48, or 72 h with different dilutions of eluates prepared from the three materials. Cellular viability, mobility, and proliferation were assessed in vitro using the Alamar Blue assay and a wound-healing test. The cells were also cultured in direct contact with the surface of each material. These were then analyzed via Scanning Electron Microscopy (SEM), and the surface chemical composition was determined by Energy-Dispersive Spectroscopy (EDS). Results: Cells incubated in the presence of eluates extracted from ProRoot MTA and PulpGuard presented rates of viability comparable to those of control cells; in contrast, undiluted Biodentine eluates induced a significant reduction of cellular viability. The wound-healing assay revealed that eluates from ProRoot MTA and PulpGuard allowed for unhindered cellular migration and proliferation. Cellular adhesion was observed on the surface of all materials tested. Consistent with their disclosed composition, EDS analysis found high relative abundance of calcium in Biodentine and ProRoot MTA and high abundance of silicon in PulpGuard. Significant amounts of zinc and calcium were also present in PulpGuard discs. Concerning solubility, Biodentine and ProRoot MTA presented mild weight loss after eluate extraction, while PulpGuard discs showed significant water uptake. Conclusions: PulpGuard displayed a good in vitro cytocompatibility profile and did not significantly affect the proliferation and migration rates of APCs. Cells cultured in the presence of PulpGuard eluates displayed a similar profile to those cultured with eluates from the widely used endodontic cement ProRoot MTA.

scholarly journals Application of piezoelectric cells printing on three-dimensional porous bioceramic scaffold for bone regeneration

2019 ◽  
Vol 5 (2) ◽  
pp. 22 ◽  
Author(s):  
Ming-You Shie ◽  
Hsin-Yuan Fang ◽  
Yen-Hong Lin ◽  
Alvin Kai-Xing Lee ◽  
Joyce Yu ◽  
...  
Keyword(s):  
Cell Attachment ◽  
Three Dimensional ◽  
Fluorescein Isothiocyanate ◽  
Cellular Adhesion ◽  
Additive Manufacture ◽  
Cell Printing ◽  
Ceramic Scaffold ◽  
Porous Bioceramic ◽  
Bone Structures ◽  
Extrusion Technology

In recent years, the additive manufacture was popularly used in tissue engineering, as the various technologies for this field of research can be used. The most common method is extrusion, which is commonly used in many bioprinting applications, such as skin. In this study, we combined the two printing techniques; first, we use the extrusion technology to form the ceramic scaffold. Then, the stem cells were printed directly on the surface of the ceramic scaffold through a piezoelectric nozzle. We also evaluated the effects of polydopamine (PDA)-coated ceramic scaffolds for cell attachment after printing on the surface of the scaffold. In addition, we used fluorescein isothiocyanate to simulate the cell adhered on the scaffold surface after ejected by a piezoelectric nozzle. Finally, the attachment, growth, and differentiation behaviors of stem cell after printing on calcium silicate/polycaprolactone (CS/PCL) and PDACS/PCL surfaces were also evaluated. The PDACS/PCL scaffold is more hydrophilic than the original CS/PCL scaffold that provided for better cellular adhesion and proliferation. Moreover, the cell printing technology using the piezoelectric nozzle, the different cells can be accurately printed on the surface of the scaffold that provided and analyzed more information of the interaction between different cells on the material. We believe that this method may serve as a useful and effective approach for the regeneration of defective complex hard tissues in deep bone structures.

Effect of in vitro culture on a chondrocyte-fibrin glue hydrogel for cartilage repair

2009 ◽  
Vol 18 (10) ◽  
pp. 1400-1406 ◽  
Author(s):  
Celeste Scotti ◽  
Laura Mangiavini ◽  
Federica Boschetti ◽  
Francesca Vitari ◽  
Cinzia Domeneghini ◽  
...  
Keyword(s):  
In Vitro Culture ◽  
Fibrin Glue ◽  
Cartilage Repair

scholarly journals Xenopus embryonic cell adhesion to fibronectin: position-specific activation of RGD/synergy site-dependent migratory behavior at gastrulation.

1996 ◽  
Vol 134 (1) ◽  
pp. 227-240 ◽  
Author(s):  
J W Ramos ◽  
D W DeSimone
Keyword(s):  
Cell Adhesion ◽  
Matrix Protein ◽  
Marginal Zone ◽  
Cell Attachment ◽  
Extracellular Matrix Protein ◽  
Mesoderm Induction ◽  
Type Iii ◽  
Basic Body ◽  
And Migration

During Xenopus laevis gastrulation, the basic body plan of the embryo is generated by movement of the marginal zone cells of the blastula into the blastocoel cavity. This morphogenetic process involves cell adhesion to the extracellular matrix protein fibronectin (FN). Regions of FN required for the attachment and migration of involuting marginal zone (IMZ) cells were analyzed in vitro using FN fusion protein substrates. IMZ cell attachment to FN is mediated by the Arg-Gly-Asp (RGD) sequence located in the type III-10 repeat and by the Pro-Pro-Arg-Arg-Ala-Arg (PPRRAR) sequence in the type III-13 repeat of the Hep II domain. IMZ cells spread and migrate persistently on fusion proteins containing both the RGD and synergy site sequence Pro-Pro-Ser-Arg-Asn (PPSRN) located in the type III-9 repeat. Cell recognition of the synergy site is positionally regulated in the early embryo. During gastrulation, IMZ cells will spread and migrate on FN whereas presumptive pre-involuting mesoderm, vegetal pole endoderm, and animal cap ectoderm will not. However, animal cap ectoderm cells acquire the ability to spread and migrate on the RGD/synergy region when treated with the mesoderm inducing factor activin-A. These data suggest that mesoderm induction activates the position-specific recognition of the synergy site of FN in vivo. Moreover, we demonstrate the functional importance of this site using a monoclonal antibody that blocks synergy region-dependent cell spreading and migration on FN. Normal IMZ movement is perturbed when this antibody is injected into the blastocoel cavity indicating that IMZ cell interaction with the synergy region is required for normal gastrulation.

Effect of 5-azacytidine on gene expression in marrow stromal cells

1989 ◽  
Vol 9 (6) ◽  
pp. 2748-2751
Author(s):  
D F Andrews ◽  
J Nemunaitis ◽  
C Tompkins ◽  
J W Singer
Keyword(s):  
Stromal Cells ◽  
Time Course ◽  
Matrix Protein ◽  
Interleukin 1 ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Marrow Stromal Cells ◽  
Necrosis Factor Alpha ◽  
Factor Alpha

When exposed to 5-azacytidine, marrow stromal cells from active long-term marrow cultures and cell lines derived from simian virus 40-transformed stromal cells rapidly upregulated c-abl and interleukin-6 transcripts while downregulating the expression of collagen I, a major matrix protein. Similar effects occurred with interleukin-1 alpha and tumor necrosis factor alpha, although the time course was considerably prolonged.

Restrictin: a chick neural extracellular matrix protein involved in cell attachment co-purifies with the cell recognition molecule F11

Development ◽  
1991 ◽  
Vol 113 (1) ◽  
pp. 151-164 ◽  
Author(s):  
F.G. Rathjen ◽  
J.M. Wolff ◽  
R. Chiquet-Ehrismann
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Matrix Protein ◽  
Cell Attachment ◽  
Extracellular Matrix Protein ◽  
Relative Molecular Mass ◽  
Adhesion Assay ◽  
Cell Recognition ◽  
Neural Extracellular Matrix ◽  
Recognition Molecule

We report here the characterization of restrictin, a novel chick neural extracellular matrix glycoprotein associated with the cell recognition molecule F11. Immunoaffinity chromatography using monoclonal antibody 23–13 directed to restrictin yield a major relative molecular mass band at 170 × 10(3) and minor bands at 160, 180, 250 and 320 × 10(3) which are immunologically related to each other. Neural cells attach on immobilized restrictin in a short-term adhesion assay. This adhesion can be blocked specifically by monoclonal or polyclonal antibodies to restrictin but not by antibodies to F11 or by the peptide GRGDSP. Antibodies to restrictin do not interfere with the fasciculation of retinal axons and the isolated restrictin does not stimulate the outgrowth of axons. In the developing nervous system, restrictin is localized in very restricted regions and is found within areas of F11 expression. The timing and pattern of expression of restrictin and its cell attachment activity suggest that it participates in developmental events of the nervous system.

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