Biologization of Pcl-Mesh Using Platelet Rich Fibrin (Prf) Enhances Its Regenerative Potential In Vitro

Introduction: Resorbable synthetic scaffolds are promising for different indications, especially in the context of bone regeneration. However, they require additional biological components to enhance their osteogenic potential. In addition to different cell types, autologous blood-derived matrices offer many advantages to enhance the regenerative capacity of biomaterials. The present study aimed to analyze whether biologization of a PCL-mesh coated using differently centrifuged Platelet rich fibrin (PRF) matrices will have a positive influence on primary human osteoblasts activity in vitro. A polymeric resorbable scaffold (Osteomesh, OsteoporeTM (OP), Singapore) was combined with differently centrifuged PRF matrices to evaluate the additional influence of this biologization concept on bone regeneration in vitro. Peripheral blood of three healthy donors was used to gain PRF matrices centrifuged either at High (710× g, 8 min) or Low (44× g, 8 min) relative centrifugal force (RCF) according to the low speed centrifugation concept (LSCC). OP-PRF constructs were cultured with pOBs. POBs cultured on the uncoated OP served as a control. After three and seven days of cultivation, cell culture supernatants were collected to analyze the pOBs activity by determining the concentrations of VEGF, TGF-β1, PDGF, OPG, IL-8, and ALP- activity. Immunofluorescence staining was used to evaluate the Osteopontin expression of pOBs. After three days, the group of OP+PRFLow+pOBs showed significantly higher expression of IL-8, TGF-ß1, PDGF, and VEGF compared to the group of OP+PRFHigh+pOBs and OP+pOBs. Similar results were observed on day 7. Moreover, OP+PRFLow+pOBs exhibited significantly higher activity of ALP compared to OP+PRFHigh+pOBs and OP+pOBs. Immunofluorescence staining showed a higher number of pOBs adherent to OP+PRFLow+pOBs compared to the groups OP+PRFHigh+pOBs and OP+pOBs. To the best of our knowledge, this study is the first to investigate the osteoblasts activity when cultured on a PRF-coated PCL-mesh in vitro. The presented results suggest that PRFLow centrifuged according to LSCC exhibits autologous blood cells and growth factors, seem to have a significant effect on osteogenesis. Thereby, the combination of OP with PRFLow showed promising results to support bone regeneration. Further in vivo studies are required to verify the results and carry out potential results for clinical translation.

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Three-Dimensional Zirconia-Based Scaffolds for Load-Bearing Bone-Regeneration Applications: Prospects and Challenges

Materials ◽

10.3390/ma14123207 ◽

2021 ◽

Vol 14 (12) ◽

pp. 3207

Author(s):

Kumaresan Sakthiabirami ◽

Vaiyapuri Soundharrajan ◽

Jin-Ho Kang ◽

Yunzhi Peter Yang ◽

Sang-Won Park

Keyword(s):

Bone Regeneration ◽

Biological Activities ◽

Three Dimensional ◽

In Vivo Studies ◽

High Mechanical Strength ◽

Real World Applications ◽

3D Fabrication ◽

Dental Applications

The design of zirconia-based scaffolds using conventional techniques for bone-regeneration applications has been studied extensively. Similar to dental applications, the use of three-dimensional (3D) zirconia-based ceramics for bone tissue engineering (BTE) has recently attracted considerable attention because of their high mechanical strength and biocompatibility. However, techniques to fabricate zirconia-based scaffolds for bone regeneration are in a stage of infancy. Hence, the biological activities of zirconia-based ceramics for bone-regeneration applications have not been fully investigated, in contrast to the well-established calcium phosphate-based ceramics for bone-regeneration applications. This paper outlines recent research developments and challenges concerning numerous three-dimensional (3D) zirconia-based scaffolds and reviews the associated fundamental fabrication techniques, key 3D fabrication developments and practical encounters to identify the optimal 3D fabrication technique for obtaining 3D zirconia-based scaffolds suitable for real-world applications. This review mainly summarized the articles that focused on in vitro and in vivo studies along with the fundamental mechanical characterizations on the 3D zirconia-based scaffolds.

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3D PCL/fish collagen composite scaffolds incorporating osteogenic abalone protein hydrolysates for bone regeneration application: in vitro and in vivo studies

Journal of Biomaterials Science Polymer Edition ◽

10.1080/09205063.2020.1834908 ◽

2020 ◽

pp. 1-17

Author(s):

Gun-Woo Oh ◽

Van-Tinh Nguyen ◽

Seong-Yeong Heo ◽

Seok-Chun Ko ◽

Chang Su Kim ◽

...

Keyword(s):

Bone Regeneration ◽

Protein Hydrolysates ◽

In Vivo Studies ◽

Composite Scaffolds ◽

Fish Collagen

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In-vitro and in-vivo studies of PLA / PCL / gelatin composite scaffold containing ascorbic acid for bone regeneration

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2020.102077 ◽

2020 ◽

pp. 102077 ◽

Cited By ~ 1

Author(s):

Seyedeh Fatemeh Hashemi ◽

Mohsen Mehrabi ◽

Arian Ehterami ◽

Anneh Mohammad Gharravi ◽

Fateme Sadat Bitaraf ◽

...

Keyword(s):

Ascorbic Acid ◽

Bone Regeneration ◽

Composite Scaffold ◽

In Vivo Studies

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Isopsoralen Enhanced Osteogenesis by Targeting AhR/ERα

Molecules ◽

10.3390/molecules23102600 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2600 ◽

Cited By ~ 8

Author(s):

Luna Ge ◽

Yazhou Cui ◽

Kai Cheng ◽

Jinxiang Han

Keyword(s):

Osteoblast Differentiation ◽

Estrogen Receptor Alpha ◽

Biological Effects ◽

Hormone Deficiency ◽

In Vivo Studies ◽

Osteogenic Potential ◽

Type I ◽

Dependent Manner

Isopsoralen (IPRN), one of the main effective ingredients in Psoralea corylifolia Linn, has a variety of biological effects, including antiosteoporotic effects. In vivo studies show that IPRN can increase bone strength and trabecular bone microstructure in a sex hormone deficiency-induced osteoporosis model. However, the mechanism underlying this osteogenic potential has not been investigated in detail. In the present study, we investigated the molecular mechanism of IPRN-induced osteogenesis in MC3T3-E1 cells. Isopsoralen promoted osteoblast differentiation and mineralization, increased calcium nodule levels and alkaline phosphatase (ALP) activity and upregulated osteoblast markers, including ALP, runt-related transcription factor 2 (RUNX2), and collagen type I alpha 1 chain (COL1A1). Furthermore, IPRN limited the nucleocytoplasmic shuttling of aryl hydrocarbon receptor (AhR) by directly binding to AhR. The AhR target gene cytochrome P450 family 1 subfamily A member 1 (CYP1A1) was also inhibited in vitro and in vivo. This effect was inhibited by the AhR agonists indole-3-carbinol (I3C) and 3-methylcholanthrene (3MC). Moreover, IPRN also increased estrogen receptor alpha (ERα) expression in an AhR-dependent manner. Taken together, these results suggest that IPRN acts as an AhR antagonist and promotes osteoblast differentiation via the AhR/ERα axis.

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Osteogenic Potential of Multipotent Adult Progenitor Cells for Calvaria Bone Regeneration

Advances in Medicine ◽

10.1155/2016/2803081 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11

Author(s):

Dong Joon Lee ◽

Yonsil Park ◽

Wei-Shou Hu ◽

Ching-Chang Ko

Keyword(s):

Bone Regeneration ◽

Progenitor Cells ◽

Adult Stem Cells ◽

Single Cells ◽

Osteogenic Potential ◽

Type I ◽

Differentiation Potential ◽

Multipotent Adult Progenitor Cells

Osteogenic cells derived from rat multipotent adult progenitor cells (rMAPCs) were investigated for their potential use in bone regeneration. rMAPCs are adult stem cells derived from bone marrow that have a high proliferation capacity and the differentiation potential to multiple lineages. They may also offer immunomodulatory properties favorable for applications for regenerative medicine. rMAPCs were cultivated as single cells or as 3D aggregates in osteogenic media for up to 38 days, and their differentiation to bone lineage was then assessed by immunostaining of osteocalcin and collagen type I and by mineralization assays. The capability of rMAPCs in facilitating bone regeneration was evaluatedin vivoby the direct implantation of multipotent adult progenitor cell (MAPC) aggregates in rat calvarial defects. Bone regeneration was examined radiographically, histologically, and histomorphometrically. Results showed that rMAPCs successfully differentiated into osteogenic lineage by demonstrating mineralized extracellular matrix formationin vitroand induced new bone formation by the effect of rMAPC aggregatesin vivo. These outcomes confirm that rMAPCs have a good osteogenic potential and provide insights into rMAPCs as a novel adult stem cell source for bone regeneration.

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Development of Porous Beads to Provide Regulated BMP-2 Stimulation for Varying Durations: In Vitro and In Vivo Studies for Bone Regeneration

Biomacromolecules ◽

10.1021/acs.biomac.6b00009 ◽

2016 ◽

Vol 17 (5) ◽

pp. 1633-1642 ◽

Cited By ~ 14

Author(s):

Ho Yong Kim ◽

Jin Ho Lee ◽

Jeong-Won Yun ◽

Jin-Ho Park ◽

Bong-Wook Park ◽

...

Keyword(s):

Bone Regeneration ◽

In Vivo Studies ◽

Porous Beads

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Role of Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) in the Bone Regeneration: A Systematic Review from 2007-2018

Annual Research & Review in Biology ◽

10.9734/arrb/2019/v31i230045 ◽

2019 ◽

pp. 1-16

Author(s):

Ismail Hadisoebroto Dilogo ◽

Jessica Fiolin

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Bone Regeneration ◽

Conditioned Medium ◽

Bone Healing ◽

In Vitro Studies ◽

In Vivo Studies

Background: The therapeutic value of mesenchymal stem cells (MSCs) in tissue engineering and regenerative medicine is attributable in part to paracrine pathways triggered by several secreted factors secreted into culture media. The secreted factor here is known as the conditioned medium (CM) or secretome. Objectives: This review is aimed to investigate and summarise the in-vitro, pre-clinical in-vivo studies regarding the role of CM-MSC in bone regeneration from 2007 until 2018 Data Sources: A systematic literature search on PubMed, MEDLINE, OVID, Scopus and Cochrane library was carried out by using search terms: Secretome, conditioned medium, mesenchymal stem cell, bone healing, osteogenic, osteogenesis. Methods: A total of 611 articles were reviewed. Ten articles were identified as relevant for this systematic literature review. Results: Three tables of studies were constructed for in vitro studies and in-vivo studies. Conclusion: All of the included in-vitro studies and in-vivo studies have shown a promoting effect of bone regeneration at various stages. Although there are no clinical studies regarding the use of CM-MSC in the human bone regeneration that have been conducted, transplantation of secretome has shown a promising result in the acceleration of bone healing process.

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Increased BMSC Exosomal miR-140-3p Alleviates Bone Degradation and Promotes Bone Restoration by Targeting Plxnb1 in Diabetic Rats

10.21203/rs.3.rs-1073550/v1 ◽

2021 ◽

Author(s):

Ning Wang ◽

Xuanchen Liu ◽

Zhen Tang ◽

Xinghui Wei ◽

Hui Dong ◽

...

Keyword(s):

Diabetes Mellitus ◽

Bone Formation ◽

Bone Regeneration ◽

Bone Defect ◽

Diabetic Rats ◽

Osteogenic Potential ◽

Bone Degradation ◽

Defect Repair

Abstract Background: Diabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participate in osteoblastogenesis and modulating bone formation. However, their impacts on the development of bone degeneration in DM are not yet known. The role of miRNAs in BMSCs exosomes on regulating hyperglycemia bone degeneration was investigated in the present study. Results: The osteogenic potential in bone defect repair of exosomes derived from diabetes mellitus BMSCs derived exosomes (DM-Exos) were revealed to be lower than that in normal BMSCs derived exosomes (N-Exos) in vitro and in vivo. Here, we demonstrate that miR-140-3p level was significantly altered in exosomes derived from BMSCs, ADSCs and serum from DM rats. In in vitro experiments, upregulated miR-140-3p exosomes promoted DM BMSCs differentiation into osteoblasts. The effects were exerted by miR-140-3p targeting plxnb1, plexin B1 is the receptor of semaphoring 4D(Sema4D) that inhibited osteocytes differentiation, thereby promoting bone formation. In DM rats with bone defect, miR-140-3p upregulated exosomes were transplanted into injured bone and accelerated bone regeneration. Besides, miR-140-3p in the exosomes was transferred into BMSCs and osteoblasts and promoted bone regeneration by targeting the plexin B1/RohA/ROCK signaling pathway. Conclusions: Normal-Exos and miR-140-3p overexpressed-Exos accelerated diabetic wound healing by promoting the osteoblastogenesis function of BMSCs through inhibition plexin B1 expression which is the receptor of Sema4D and the plexin B1/RhoA/ROCK pathway compared with diabetes mellitus-Exos. This offers a new insight and a new therapy for treating diabetic bone unhealing.

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