scholarly journals Preclinical Evaluation of the Safety and Immunological Action of Allogeneic ADSC-Collagen Scaffolds in the Treatment of Chronic Ischemic Cardiomyopathy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1269
Author(s):  
Ascensión López-Díaz de Cerio ◽  
Iñigo Perez-Estenaga ◽  
Susana Inoges ◽  
Gloria Abizanda ◽  
Juan José Gavira ◽  
...  
Keyword(s):  
Immunological Response ◽  
Collagen Scaffold ◽  
Tumor Formation ◽  
Future Application ◽  
Collagen Scaffolds ◽  
Cell Engraftment ◽  
Human Adscs ◽  
Natural Support ◽  
Immunomodulatory Action ◽  
Lymphocyte Responses

The use of allogeneic adipose-derived mesenchymal stromal cells (alloADSCs) represents an attractive approach for treating myocardial infarction (MI). Furthermore, adding a natural support improves alloADSCs engraftment and survival in heart tissues, leading to a greater therapeutic effect. We aimed to examine the safety and immunological reaction induced by epicardial implantation of a clinical-grade collagen scaffold (CS) seeded with alloADSCs for its future application in humans. Thus, cellularized scaffolds were myocardially or subcutaneously implanted in immunosuppressed rodent models. The toxicological parameters were not significantly altered, and tumor formation was not found over the short or long term. Furthermore, biodistribution analyses in the infarcted immunocompetent rats displayed cell engraftment in the myocardium but no migration to other organs. The immunogenicity of alloADSC-CS was also evaluated in a preclinical porcine model of chronic MI; no significant humoral or cellular alloreactive responses were found. Moreover, CS cellularized with human ADSCs cocultured with human allogeneic immune cells produced no alloreactive response. Interestingly, alloADSC-CS significantly inhibited lymphocyte responses, confirming its immunomodulatory action. Thus, alloADSC-CS is likely safe and does not elicit any alloreactive immunological response in the host. Moreover, it exerts an immunomodulatory action, which supports its translation to a clinical setting.

In vivo Evaluation of a Collagen Scaffold Preconditioned with Adipose-derived Mesenchymal Stem Cells Used for Bone Regeneration A histological study

2018 ◽  
Vol 55 (4) ◽  
pp. 691-695
Author(s):  
Tudor Sorin Pop ◽  
Anca Maria Pop ◽  
Alina Dia Trambitas Miron ◽  
Klara Brinzaniuc ◽  
Simona Gurzu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Histological Study ◽  
Collagen Scaffold ◽  
Bone Defects ◽  
Collagen Scaffolds ◽  
In Vivo Evaluation ◽  
Calvarial Bone ◽  
Bone Apposition

The use of collagen scaffolds and stem cells for obtaining a tissue-engineering complex has been an important concept in promoting repair and regeneration of the bone tissue. Such units represent important steps in the development of an ideal scaffold-cell complex that would sustain new bone apposition. The aim of our study was to perform a histologic evaluation of the healing of critical-sized bone defects, using a biologic collagen scaffold with adipose-derived mesenchymal stem cells, in comparison to negative controls created in the adjacent bone. We used 16 Wistar rats and according to the study design 2 calvarial bone defects were created in each animal, one was filled with collagen seeded with adipose-derived stem cells and the other one was considered negative control. During the following month, at weekly intervals, the animals were euthanized and the specimens from bone defects were histologically evaluated. The results showed that these scaffolds were highly biocompatible as only moderate inflammation no rejection reactions were observed. Furthermore, the first signs of osseous healing appeared after two weeks accompanied by angiogenesis. Collagen scaffolds seeded with adipose-derived mesenchymal stem cells can be considered a promising treatment option in bone regeneration of large defects.

scholarly journals Optimization of Collagen Chemical Crosslinking to Restore Biocompatibility of Tissue-Engineered Scaffolds

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 832
Author(s):  
Mohammad Mirazul Islam ◽  
Dina B. AbuSamra ◽  
Alexandru Chivu ◽  
Pablo Argüeso ◽  
Claes H. Dohlman ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Crosslinking Agent ◽  
Collagen Scaffold ◽  
Human Monocyte ◽  
Subsequent Treatment ◽  
Sodium Metabisulfite ◽  
Corneal Tissue ◽  
Dependent Manner ◽  
Collagen Scaffolds ◽  
Enzymatic Stability

Collagen scaffolds, one of the most used biomaterials in corneal tissue engineering, are frequently crosslinked to improve mechanical properties, enzyme tolerance, and thermal stability. Crosslinkers such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) are compatible with tissues but provide low crosslinking density and reduced mechanical properties. Conversely, crosslinkers such as glutaraldehyde (GTA) can generate mechanically more robust scaffolds; however, they can also induce greater toxicity. Herein, we evaluated the effectivity of double-crosslinking with both EDC and GTA together with the capability of sodium metabisulfite (SM) and sodium borohydride (SB) to neutralize the toxicity and restore biocompatibility after crosslinking. The EDC-crosslinked collagen scaffolds were treated with different concentrations of GTA. To neutralize the free unreacted aldehyde groups, scaffolds were treated with SM or SB. The chemistry involved in these reactions together with the mechanical and functional properties of the collagen scaffolds was evaluated. The viability of the cells grown on the scaffolds was studied using different corneal cell types. The effect of each type of scaffold treatment on human monocyte differentiation was evaluated. One-way ANOVA was used for statistical analysis. The addition of GTA as a double-crosslinking agent significantly improved the mechanical properties and enzymatic stability of the EDC crosslinked collagen scaffold. GTA decreased cell biocompatibility but this effect was reversed by treatment with SB or SM. These agents did not affect the mechanical properties, enzymatic stability, or transparency of the double-crosslinked scaffold. Contact of monocytes with the different scaffolds did not trigger their differentiation into activated macrophages. Our results demonstrate that GTA improves the mechanical properties of EDC crosslinked scaffolds in a dose-dependent manner, and that subsequent treatment with SB or SM partially restores biocompatibility. This novel manufacturing approach would facilitate the translation of collagen-based artificial corneas to the clinical setting.

scholarly journals Autologous Tenocyte Implantation (ATI) and the Use of Collagen Scaffolds: a Case Report of a Novel Surgical Treatment for Gluteal Tendon Repair

2021 ◽  
pp. 194
Author(s):  
◽  
◽  
◽  
◽  
Keyword(s):  
Platelet Rich Plasma ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Collagen Scaffold ◽  
Gluteus Medius ◽  
Normal Function ◽  
Collagen Scaffolds ◽  
Mri Findings ◽  
Level Of Evidence ◽  
Mri Scans

Background: Ortho-biological therapies such as platelet-rich plasma and autologous tenocyte implantation injections are hypothesized to introduce cellular mediators such as growth factors into tendons, promoting natural healing. Methods: This case introduces a 63-year-old female with an extensive history of lateral hip pain and treatment refractory tendinopathy with tearing. She underwent open surgery to repair the gluteus medius tendon, using supplementary autologous tenocyte implantation (ATI) in conjunction with a Celgro (Orthocell, Perth, Australia) collagen scaffold. Level of evidence: 4 Results: She had normal function in the hip at 12 months. MRI scans post-operatively at 12 months showed a marked reduction in inflammation, an intact tendon and a reduction in atrophic changes in the muscle belly. Conclusion: Surgical repair of a large degenerate tear of the gluteus medius tendon, augmented with autologous tenocyte implantation in a collagen scaffold led to an excellent patient outcome and MRI findings demonstrated tendon healing with improved tendon structure and reduced inflammation.

scholarly journals Dendrimer Functionalized Metal Oxide Nanoparticle mediated Self-Assembled Collagen Scaffold for Skin Regenerative Application: Function of Metal in Metal oxides

2021 ◽  
Author(s):  
KJ Sree ◽  
Mohan Vedhanayagam ◽  
Balachandran Unni Nair ◽  
Anandasadagopan Suresh kumar
Keyword(s):  
Metal Oxide ◽  
Mechanical Strength ◽  
Cell Viability ◽  
Metal Oxide Nanoparticles ◽  
Collagen Scaffold ◽  
Albino Rats ◽  
Oxide Nanoparticles ◽  
Collagen Scaffolds ◽  
Assembly Method

Abstract Functionalized metal oxide nanoparticles cross-linked collagen scaffolds are widely used in skin regenerative applications because of their enhanced physico-chemical and biocompatibility properties. From the safety clinical trials point of view, there are no reports that have compared the effects of functionalized metal oxide nanoparticles mediated collagen scaffolds for in-vivo skin regenerative applications. In this work, Triethoxysilane - Poly (amido amine) dendrimer generation 3 (TES-PAMAM -G3 or G3) functionalized spherical shape metal oxide nanoparticles (MO NPs: ZnO, TiO2, Fe3O4, CeO2, and SiO2, Size: 12 -25 nm) cross-linked collagen scaffolds were prepared by using a self-assembly method. Triple helical conformation, pore size, mechanical strength and in-vitro cell viability of MO-TES-PAMAM-G3- collagen scaffolds were studied through different methods. The in-vivo skin regenerative proficiency of MO-TES-PAMAM-G3- collagen scaffolds were analysed by implanting the scaffold on wounds in Wistar Albino rats. The results demonstrated that MO-TES-PAMAM-G3- collagen scaffold showed superior skin regeneration properties than other scaffolds. The skin regenerative efficiency of MO NPs followed order: ZnO> TiO2> CeO2> SiO2> Fe3O4 NPs. This result can be attributed to higher mechanical strength, cell –viability and better antibacterial activity of ZnO-TES-PAMAM-G3-collagen scaffold lead to accelerate the skin regenerative properties in comparison to other metal oxide based collagen scaffolds.

scholarly journals Generation of a three-dimensional collagen scaffold-based model of the human endometrium

2020 ◽  
Vol 10 (2) ◽  
pp. 20190079 ◽  
Author(s):  
Yassen Abbas ◽  
Lucia G. Brunel ◽  
Michael S. Hollinshead ◽  
Ridma C. Fernando ◽  
Lucy Gardner ◽  
...  
Keyword(s):  
Average Pore Size ◽  
Three Dimensional ◽  
Collagen Scaffold ◽  
Study Finding ◽  
Cell Types ◽  
Apical Surface ◽  
Collagen Scaffolds ◽  
Average Pore ◽  
Stromal Cell Culture ◽  
Optimal Average

The endometrium is the secretory lining of the uterus that undergoes dynamic changes throughout the menstrual cycle in preparation for implantation and a pregnancy. Recently, endometrial organoids (EO) were established to study the glandular epithelium. We have built upon this advance and developed a multi-cellular model containing both endometrial stromal and epithelial cells. We use porous collagen scaffolds produced with controlled lyophilization to direct cellular organization, integrating organoids with primary isolates of stromal cells. The internal pore structure of the scaffold was optimized for stromal cell culture in a systematic study, finding an optimal average pore size of 101 µm. EO seeded organize to form a luminal-like epithelial layer, on the surface of the scaffold. The cells polarize with their apical surface carrying microvilli and cilia that face the pore cavities and their basal surface attaching to the scaffold with the formation of extracellular matrix proteins. Both cell types are hormone responsive on the scaffold, with hormone stimulation resulting in epithelial differentiation and stromal decidualization.

Existing Drug Repurposing for Glioblastoma to Discover Candidate Drugs as a New Approach

2021 ◽  
Vol 18 ◽  
Author(s):  
Bo Yang ◽  
Xiande Wang ◽  
Dong Dong ◽  
Yunqing Pan ◽  
Junhua Wu ◽  
...  
Keyword(s):  
Mtt Assay ◽  
Human Cancer ◽  
Drug Repurposing ◽  
Tumor Formation ◽  
New Drugs ◽  
Algorithm Analysis ◽  
Future Application ◽  
Tunel Staining ◽  
Individualized Treatments

Aims: Repurposing of drugs has been hypothesized as a means of identifying novel treatment methods for certain diseases. Background: Glioblastoma (GB) is an aggressive type of human cancer; the most effective treatment for glioblastoma is chemotherapy. Whereas, when repurposing drugs, a lot of time and money can be saved. Objective: Repurposing of the existing drug may be used to discover candidate drugs for individualized treatments of GB. Method: We used the bioinformatics method to obtain the candidate drugs. In addition, the drugs were verified by MTT assay, Transwell® assays, TUNEL staining, and in vivo tumor formation experiments, as well as statistical analysis. Result: We obtained 4 candidate drugs suitable for the treatment of glioma: camptothecin, doxorubicin, daunorubicin, and mitoxantrone by expression spectrum data, IPAS algorithm analysis, and drug-pathway connectivity analysis. These validation experiments showed that camptothecin was more effective at treating the GB, such as MTT assay, Transwell® assays, TUNEL staining, and in vivo tumor formation. Conclusion: With regard to personalized treatment, this present study may be used to guide the research of new drugs via verification experiments and tumor formation. The present study also provides a guide to systematic, individualized drug discovery for complex diseases and may contribute to the future application of individualized treatments.

Plumbagin caged silver nanoparticle stabilized collagen scaffold for wound dressing

2015 ◽  
Vol 3 (7) ◽  
pp. 1415-1425 ◽  
Author(s):  
N. Duraipandy ◽  
Rachita Lakra ◽  
Kunnavakkam Vinjimur Srivatsan ◽  
Usha Ramamoorthy ◽  
Purna Sai Korrapati ◽  
...  
Keyword(s):  
Wound Healing ◽  
Silver Nanoparticle ◽  
Wound Dressing ◽  
Collagen Scaffold ◽  
Cross Linking ◽  
Collagen Scaffolds ◽  
Wound Healing Activity

Wound dressing material based on nano-biotechnological intervention by caging plumbagin on silver nanoparticle (PCSN) as a multi-site cross-linking agent of collagen scaffolds with potent anti-microbial and wound healing activity.

scholarly journals Bone Mesenchymal Stem Cells Contribute to Ligament Regeneration and Graft–Bone Healing after Anterior Cruciate Ligament Reconstruction with Silk–Collagen Scaffold

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Fanggang Bi ◽  
Yangdi Chen ◽  
Junqi Liu ◽  
Wenhao Hu ◽  
Ke Tian
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Collagen Scaffold ◽  
Micro Ct ◽  
Collagen Scaffolds ◽  
Bone Mesenchymal Stem Cells ◽  
Bone Integration ◽  
Anterior Cruciate

Anterior cruciate ligament (ACL) reconstruction was realized using a combination of bone mesenchymal stem cells (BMSCs) and silk–collagen scaffold, and an in vivo evaluation of this combination was performed. By combining type I collagen and degummed silk fibroin mesh, silk–collagen scaffolds were prepared to simulate ligament components. BMSCs isolated from bone marrow of rabbits were cultured for a homogenous population and seeded on the silk–collagen scaffold. In the scaffold and BMSC (S/C) group, scaffolds were seeded with BMSCs for 72 h and then rolled and used to replace the ACL in 20 rabbits. In the scaffold (S) group, scaffolds immersed only in culture medium for 72 h were used for ACL reconstruction. Specimens were collected at 4 and 16 weeks postoperatively to assess ligament regeneration and bone integration. HE and immunohistochemical staining (IHC) were performed to assess ligament regeneration in the knee cavity. To assess bone integration at the graft–bone interface, HE, Russell–Movat staining, micro-CT, and biomechanical tests were performed. After 4 weeks, vigorous cell proliferation was observed in the core part of the scaffold in the S/C group, and a quantity of fibroblast-like cells and extracellular matrix (ECM) was observed in the center part of the graft at 16 weeks after surgery. At 4 and 16 weeks postoperatively, the tenascin-C expression in the S/C group was considerably higher than that in the S group (4 w, p < 0.01 ; 16 w, p < 0.01 ). Furthermore, bone integration was better in the S/C group than in the S group, with histological observation of trabecular bone growth into the graft and more mineralized tissue formation detected by micro-CT (4 w, bone volume fraction (BV/TV), p = 0.0169 , bone mineral density (BMD), p = 0.0001 ; 16 w, BV/TV, p = 0.1233 , BMD, p = 0.0494 ). These results indicate that BMSCs promote ligament regeneration in the knee cavity and bone integration at the graft–bone interface. Silk–collagen scaffolds and BMSCs will likely be combined for clinical practice in the future.

scholarly journals Evaluation of antitumor activity in strains of a new rotavirus group in Reoviridae family on a model of transplantable murine melanoma

2020 ◽  
Vol 66 (6) ◽  
pp. 712-717
Author(s):  
Sergei Kolpakov ◽  
Elena Kolpakova ◽  
Elena Zlatnik ◽  
Evgeniya Nepomnyashchaya ◽  
Inna Novikova ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Morphological Characteristics ◽  
Culture Fluid ◽  
Tumor Formation ◽  
Antitumor Effects ◽  
Murine Melanoma ◽  
Lytic Effect ◽  
Viral Particles ◽  
Immunomodulatory Action ◽  
Extensive Necrosis

The purpose was to study antitumor effects of the group K rotaviruses strains No. 228 and No. 100 in the experiment on a model of transplantable murine melanoma. Material and methods. The study included 65 С57Black/6 mice with transplantable B16/F10 melanoma and two strains of the Reoviridae family members characterized as rotaviruses, not belonging to the known groups, with the working title “group K rotaviruses (RVK)”. Animals received RVK in “vaccination” (before tumor transplantation) and “treatment” (after tumor formation) modes. Live and inactivated strains were used. RVK were administered intramuscularly as 0.3 ml of virus-containing culture fluid with at least 5x109 viral particles per 1 ml, with a total of 4 injections. Life span of mice and morphological characteristics of tumors were evaluated. Results. Injections of both strains increased the survival of tumor-bearing mice by 1.7-1.9 times in 4 of 8 experimental groups, compared to controls. The modes of RVK administration showed some differences: the survival was longer in mice with the “vaccination” mode compared to the “treatment” mode. Morphological changes in tumors were similar after application of both modes and inclued dystrophic changes of tumor cells, formation of extensive necrosis areas, and leukocyte infiltration. Discussion. Live and inactivated RVK had unidirectional effects implying its association with immunomodulatory action rather than with a direct lytic effect on the tumor. Conclusions. Both studied strains of rotaviruses in the group K had antitumor effect in the model of transplantable В16/F10 murine melanoma in the «vaccination» mode.

Effects of radiation dose and nitrogen purge on collagen scaffold properties

2021 ◽  
pp. 088532822110476
Author(s):  
Nicholas J Sant ◽  
Benedikt L Proffen ◽  
Martha M Murray
Keyword(s):  
Radiation Dose ◽  
Enzymatic Degradation ◽  
Early Stage ◽  
Collagen Scaffold ◽  
Radiation Doses ◽  
Collagen Scaffolds ◽  
Banding Patterns ◽  
Soluble Collagen ◽  
Mass Fractions ◽  
Effects Of Radiation

Sterilization of medical devices is commonly performed using radiation methods. However, collagen materials can be damaged when using standard radiation doses (25 kGy). Small increases of radiation dose can allow for increases in the acceptable initial bioburden load of aseptically manufactured devices while maintaining required sterility assurance levels, which is often critical in early stage translational settings. In this study, we hypothesized that small increases in radiation dose from 15 to 20 kGy would result in significant changes to several key characteristics of collagen scaffolds. Scaffolds were manufactured by lyophilizing the pepsin digest of dense bovine connective tissue in cylindrical molds and were irradiated at either 0, 15, 17.5, or 20 kGy with an additional group packaged in nitrogen and irradiated at 17.5 kGy. Groups were evaluated for changes to the soluble collagen and glycosaminoglycan mass fractions, protein banding patterns in electrophoresis, a collagen fragmentation assay, and resistance to enzymatic degradation. All parameters were statistically analyzed using one-way analysis of variance with Tukey’s correction for multiple comparisons. The soluble collagen mass fraction was significantly decreased in the 20 kGy group; however, there was no significant effect of radiation dose or a nitrogen-rich environment on the other measured parameters, including protein banding patterns, fragmented collagen content, and resistance to enzymatic degradation. Statement of Clinical Significance: Collagen scaffolds have proven useful in clinical applications but can be damaged by standard radiation doses. Low-dose sterilization may be a viable alternative that minimally impacts key properties of these scaffolds.

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