Sustained low-dose dexamethasone delivery via a PLGA microsphere-embedded agarose implant for enhanced osteochondral repair

Stefani, Robert M.; Lee, Andy J.; Tan, Andrea R.; Halder, Saiti S.; Hu, Yizhong; Guo, Xing; Stoker, Aaron M.; Ateshian, Gerard A.; Marra, Kacey G.; Cook, James L.; Hung, Clark T.

doi:10.1016/j.actbio.2019.11.052

Cited by 65 publications

(55 citation statements)

References 78 publications

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“…PLGA is hydrolyzed into lactic acid and glycolic acid in vivo, and further metabolized into water and carbon dioxide through the tricarboxylic acid cycle, and finally excreted in the lung. The safety of PLGA has been recognized by the United States Food and Drug Administration(FDA) and the European Medicines Agency, and has now been officially included by the FDA as a pharmaceutical excipient (Han et al, 2016;Ruman et al, 2020;Stefani et al, 2020). The properties of PLGA can be changed by adjusting the monomer ratio (LA/GA), molecular weight (M W ), concentration, and terminal group, which will affect the encapsulation efficiency (EE%) and drug release kinetics of PLGA microspheres (Li et al, 2021).…”

Section: Plga As Biodegradable Microsphere Carrier Materialsmentioning

confidence: 99%

PLGA-based biodegradable microspheres in drug delivery: recent advances in research and application

Zhang²,

Sun³

et al. 2021

Drug Delivery

305

106

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Biodegradable microspheres have been widely used in the field of medicine due to their ability to deliver drug molecules of various properties through multiple pathways and their advantages of low dose and low side effects. Poly (lactic-co-glycolic acid) copolymer (PLGA) is one of the most widely used biodegradable material currently and has good biocompatibility. In application, PLGA with a specific monomer ratio (lactic acid and glycolic acid) can be selected according to the properties of drug molecules and the requirements of the drug release rate. PLGA-based biodegradable microspheres have been studied in the field of drug delivery, including the delivery of various anticancer drugs, protein or peptide drugs, bacterial or viral DNA, etc. This review describes the basic knowledge and current situation of PLGA biodegradable microspheres and discusses the selection of PLGA polymer materials. Then, the preparation methods of PLGA microspheres are introduced, including emulsification, microfluidic technology, electrospray, and spray drying. Finally, this review summarizes the application of PLGA microspheres in drug delivery and the treatment of pulmonary and ocularrelated diseases.

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Section: Plga As Biodegradable Microsphere Carrier Materialsmentioning

confidence: 99%

PLGA-based biodegradable microspheres in drug delivery: recent advances in research and application

Zhang²,

Sun³

et al. 2021

Drug Delivery

305

106

View full text Add to dashboard Cite

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“…However, these materials are limited in terms of processability and manipulatable degradation time ( Pati et al, 2014 ). In contrast, synthetic polymers have good mechanical strength, controllable degradation and high plasticity ( Li et al, 2019b ; Stefani et al, 2020 ). But they also have shortcomings, such as poor biocompatibility, acidic degradation products, low biological activity, hydrophobicity and limited interfacial integration with tissue ( Stocco et al, 2014 ; Park et al, 2018 ; Lin et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Host Response to Biomaterials for Cartilage Tissue Engineering: Key to Remodeling

Liu

Chen

et al. 2021

Front. Bioeng. Biotechnol.

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Biomaterials play a core role in cartilage repair and regeneration. The success or failure of an implanted biomaterial is largely dependent on host response following implantation. Host response has been considered to be influenced by numerous factors, such as immune components of materials, cytokines and inflammatory agents induced by implants. Both synthetic and native materials involve immune components, which are also termed as immunogenicity. Generally, the innate and adaptive immune system will be activated and various cytokines and inflammatory agents will be consequently released after biomaterials implantation, and further triggers host response to biomaterials. This will guide the constructive remolding process of damaged tissue. Therefore, biomaterial immunogenicity should be given more attention. Further understanding the specific biological mechanisms of host response to biomaterials and the effects of the host-biomaterial interaction may be beneficial to promote cartilage repair and regeneration. In this review, we summarized the characteristics of the host response to implants and the immunomodulatory properties of varied biomaterial. We hope this review will provide scientists with inspiration in cartilage regeneration by controlling immune components of biomaterials and modulating the immune system.

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“…Dex also has an anticatabolic effect on cartilage in vitro. Low concentrations of Dex were able to protect cartilage explants from TNF- α and high dosage suppressed GAG content loss [ 29 ]. Black et al suggested in IL-1 α -stimulated bovine cartilage explants that Dex treatment largely inhibited transcriptions of IL-6, MMP-3, and MMP-13 [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

CypB-CD147 Signaling Is Involved in Crosstalk between Cartilage and FLS in Collagen-Induced Arthritis

Wang

Fan

et al. 2020

Mediators of Inflammation

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To investigate the crosstalk between cartilage and fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), we adopted an in vitro coculture system model of collagen-induced arthritis (CIA) cartilage and CIA FLS monolayer. CIA rat samples of the synovium and femur head were collected for isolation of FLS and coculture system. Cartilages were treated with vehicle (Ctrl group), 10 ng/mL interleukin- (IL-) 1α (IL-1α group), and 10 ng/mL IL-1α plus 10 μM dexamethasone (Dex group) for 3 days before coculture with FLS for further 2 days. After the coculture, FLS were collected to determine the influences of articular cartilage on synoviocytes. Whether the CypB-CD147 signaling pathway is involved in the interactions between cartilage and FLS is assayed. Results showed that IL-1α-stimulated CIA cartilage promoted the proliferation and reduced the apoptosis of FLS. Increased inflammatory cytokines and decreased p57 expression were found in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. Upregulation of NF-κB and I-κB kinase β (IKK-β) and downregulation of the inhibitor of NF-κBα (I-κBα) protein were observed in cocultured FLS. After coculture, significant increases in the expression of cyclophilin B (CypB) and CD147 were observed in CIA cartilage and FLS, respectively. Furthermore, results of immunofluorescence staining showed that the anti-CD147 antibody significantly suppressed p65 nuclear translocation in cocultured FLS stimulated by IL-1α-challenged CIA cartilage. In conclusion, inflammatory effects in the cartilage-FLS coculture system are associated with the CypB-CD147 mediating NF-κB pathway which may further enhance the inflammation in RA.

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Sustained low-dose dexamethasone delivery via a PLGA microsphere-embedded agarose implant for enhanced osteochondral repair

Cited by 65 publications

References 78 publications

PLGA-based biodegradable microspheres in drug delivery: recent advances in research and application

PLGA-based biodegradable microspheres in drug delivery: recent advances in research and application

Host Response to Biomaterials for Cartilage Tissue Engineering: Key to Remodeling

CypB-CD147 Signaling Is Involved in Crosstalk between Cartilage and FLS in Collagen-Induced Arthritis

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