Controlled dexamethasone delivery via double-walled microspheres to enhance long-term adipose tissue retention
Current materials used for adipose tissue reconstruction have critical shortcomings such as suboptimal volume retention, donor-site morbidity, and poor biocompatibility. The aim of this study was to examine a controlled delivery system of dexamethasone to generate stable adipose tissue when mixed wi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-10-01
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| Series: | Journal of Tissue Engineering |
| Online Access: | https://doi.org/10.1177/2041731417735402 |
| _version_ | 1819020524628475904 |
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| author | Arta Kelmendi-Doko J Peter Rubin Katarina Klett Christopher Mahoney Sheri Wang Kacey G Marra |
| author_facet | Arta Kelmendi-Doko J Peter Rubin Katarina Klett Christopher Mahoney Sheri Wang Kacey G Marra |
| author_sort | Arta Kelmendi-Doko |
| collection | DOAJ |
| description | Current materials used for adipose tissue reconstruction have critical shortcomings such as suboptimal volume retention, donor-site morbidity, and poor biocompatibility. The aim of this study was to examine a controlled delivery system of dexamethasone to generate stable adipose tissue when mixed with disaggregated human fat in an athymic mouse model for 6 months. The hypothesis that the continued release of dexamethasone from polymeric microspheres would enhance both adipogenesis and angiogenesis more significantly when compared to the single-walled microsphere model, resulting in long-term adipose volume retention, was tested. Dexamethasone was encapsulated within single-walled poly(lactic- co -glycolic acid) microspheres (Dex SW MS) and compared to dexamethasone encapsulated in a poly(lactic- co -glycolic acid) core surrounded by a shell of poly- l -lactide. The double-walled polymer microsphere system in the second model was developed to create a more sustainable drug delivery process. Dexamethasone-loaded poly(lactic- co -glycolic acid) microspheres (Dex SW MS) and dexamethasone-loaded poly(lactic- co -glycolic acid)/poly- l -lactide double-walled microspheres (Dex DW MS) were prepared using single and double emulsion/solvent techniques. In vitro release kinetics were determined. Two doses of each type of microsphere were examined; 50 and 27 mg of Dex MS and Dex DW MS were mixed with 0.3 mL of human lipoaspirate. Additionally, 50 mg of empty MS and lipoaspirate-only controls were examined. Samples were analyzed grossly and histologically after 6 months in vivo. Mass and volume were measured; dexamethasone microsphere-containing samples demonstrated greater adipose tissue retention compared to the control group. Histological analysis, including hematoxylin and eosin and CD31 staining, indicated increased vascularization (p < 0.05) within the Dex MS-containing samples. Controlled delivery of adipogenic factors, such as dexamethasone via polymer microspheres, significantly affects adipose tissue retention by maintaining healthy tissue formation and vascularization. Dex DW MS provide an improved model to former Dex SW MS, resulting in notably longer release time and, consequently, larger volumes of adipose retained in vivo. The use of microspheres, specifically double-walled, as vehicles for controlled drug delivery of adipogenic factors therefore present a clinically relevant model of adipose retention that has the potential to greatly improve soft tissue repair. |
| first_indexed | 2024-12-21T03:52:35Z |
| format | Article |
| id | doaj.art-4102be6922e049378e53f76531c1a0f8 |
| institution | Directory Open Access Journal |
| issn | 2041-7314 |
| language | English |
| last_indexed | 2024-12-21T03:52:35Z |
| publishDate | 2017-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Tissue Engineering |
| spelling | doaj.art-4102be6922e049378e53f76531c1a0f82022-12-21T19:16:55ZengSAGE PublishingJournal of Tissue Engineering2041-73142017-10-01810.1177/2041731417735402Controlled dexamethasone delivery via double-walled microspheres to enhance long-term adipose tissue retentionArta Kelmendi-Doko0J Peter Rubin1Katarina Klett2Christopher Mahoney3Sheri Wang4Kacey G Marra5Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USAMcGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USADepartment of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USADepartment of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USADepartment of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USAMcGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USACurrent materials used for adipose tissue reconstruction have critical shortcomings such as suboptimal volume retention, donor-site morbidity, and poor biocompatibility. The aim of this study was to examine a controlled delivery system of dexamethasone to generate stable adipose tissue when mixed with disaggregated human fat in an athymic mouse model for 6 months. The hypothesis that the continued release of dexamethasone from polymeric microspheres would enhance both adipogenesis and angiogenesis more significantly when compared to the single-walled microsphere model, resulting in long-term adipose volume retention, was tested. Dexamethasone was encapsulated within single-walled poly(lactic- co -glycolic acid) microspheres (Dex SW MS) and compared to dexamethasone encapsulated in a poly(lactic- co -glycolic acid) core surrounded by a shell of poly- l -lactide. The double-walled polymer microsphere system in the second model was developed to create a more sustainable drug delivery process. Dexamethasone-loaded poly(lactic- co -glycolic acid) microspheres (Dex SW MS) and dexamethasone-loaded poly(lactic- co -glycolic acid)/poly- l -lactide double-walled microspheres (Dex DW MS) were prepared using single and double emulsion/solvent techniques. In vitro release kinetics were determined. Two doses of each type of microsphere were examined; 50 and 27 mg of Dex MS and Dex DW MS were mixed with 0.3 mL of human lipoaspirate. Additionally, 50 mg of empty MS and lipoaspirate-only controls were examined. Samples were analyzed grossly and histologically after 6 months in vivo. Mass and volume were measured; dexamethasone microsphere-containing samples demonstrated greater adipose tissue retention compared to the control group. Histological analysis, including hematoxylin and eosin and CD31 staining, indicated increased vascularization (p < 0.05) within the Dex MS-containing samples. Controlled delivery of adipogenic factors, such as dexamethasone via polymer microspheres, significantly affects adipose tissue retention by maintaining healthy tissue formation and vascularization. Dex DW MS provide an improved model to former Dex SW MS, resulting in notably longer release time and, consequently, larger volumes of adipose retained in vivo. The use of microspheres, specifically double-walled, as vehicles for controlled drug delivery of adipogenic factors therefore present a clinically relevant model of adipose retention that has the potential to greatly improve soft tissue repair.https://doi.org/10.1177/2041731417735402 |
| spellingShingle | Arta Kelmendi-Doko J Peter Rubin Katarina Klett Christopher Mahoney Sheri Wang Kacey G Marra Controlled dexamethasone delivery via double-walled microspheres to enhance long-term adipose tissue retention Journal of Tissue Engineering |
| title | Controlled dexamethasone delivery via double-walled microspheres to enhance long-term adipose tissue retention |
| title_full | Controlled dexamethasone delivery via double-walled microspheres to enhance long-term adipose tissue retention |
| title_fullStr | Controlled dexamethasone delivery via double-walled microspheres to enhance long-term adipose tissue retention |
| title_full_unstemmed | Controlled dexamethasone delivery via double-walled microspheres to enhance long-term adipose tissue retention |
| title_short | Controlled dexamethasone delivery via double-walled microspheres to enhance long-term adipose tissue retention |
| title_sort | controlled dexamethasone delivery via double walled microspheres to enhance long term adipose tissue retention |
| url | https://doi.org/10.1177/2041731417735402 |
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