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Article ; Online: Release mechanisms and applications of drug delivery systems for extended-release.

Wang, Shuying / Liu, Renhe / Fu, Yao / Kao, W John

2020 Volume 17, Issue 9, Page(s) 1289–1304

Abstract: Introduction: Drug delivery systems with extended-release profiles are ideal in improving patient compliance with enhanced efficacy. To develop devices capable of a prolonged delivery kinetics, it is crucial to understand the various underlying ... ...

Abstract	Introduction: Drug delivery systems with extended-release profiles are ideal in improving patient compliance with enhanced efficacy. To develop devices capable of a prolonged delivery kinetics, it is crucial to understand the various underlying mechanisms contributing to extended drug release and the impact thereof on modulating the long-term performance of such systems in a practical application environment. Areas covered: This review article intends to provide a comprehensive summary of release mechanisms in extended-release drug delivery systems, particularly polymer-based systems; however, other material types will also be mentioned. Selected current research in the delivery of small molecule drugs and macromolecules is highlighted. Emphasis is placed on the combined impact of different release mechanisms and drug properties on the long-term release kinetics Expert opinion: The development of drug delivery systems over an extended duration is promising but also challenging when considering the numerous interrelated delivery-related parameters. Achieving a well-controlled extended drug release requires advanced techniques to minimize burst release and lag phase, a better understanding of the dynamic interrelationship between drug properties and release profiles over time, and a thorough elucidation of the impact of multiple
MeSH term(s)	Delayed-Action Preparations ; Drug Delivery Systems ; Drug Liberation ; Humans ; Polymers/chemistry
Chemical Substances	Delayed-Action Preparations ; Polymers
Language	English
Publishing date	2020-08-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2167286-6
ISSN	1744-7593 ; 1742-5247
ISSN (online)	1744-7593
ISSN	1742-5247
DOI	10.1080/17425247.2020.1788541
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Article ; Online: Combinatorial biomatrix/cell-based therapies for restoration of host tissue architecture and function.

Cantu, David Antonio / Kao, W John

Advanced healthcare materials

2013 Volume 2, Issue 12, Page(s) 1544–1563

Abstract: This Progress Report reviews recent advances in the utility of extracellular matrix (ECM)-mimic biomaterials in presenting and delivering therapeutic cells to promote tissue healing. This overview gives a brief introduction of different cell types being ... ...

Abstract	This Progress Report reviews recent advances in the utility of extracellular matrix (ECM)-mimic biomaterials in presenting and delivering therapeutic cells to promote tissue healing. This overview gives a brief introduction of different cell types being used in regenerative medicine and tissue engineering while addressing critical issues that must be overcome before cell-based approaches can be routinely employed in the clinic. A selection of five commonly used cell-associated, biomaterial platforms (collagen, hyaluronic acid, fibrin, alginate, and poly(ethylene glycol)) are reviewed for treatment of a number of acute injury or diseases with emphasis on animal models and clinical trials. This article concludes with current challenges and future perspectives regarding foreign body host response to biomaterials and immunological reactions to allogeneic or xenogeneic cells, vascularization and angiogenesis, matching mechanical strength and anisotropy of native tissues, as well as other non-technical issues regarding the clinical translation of biomatrix/cell-based therapies.
MeSH term(s)	Animals ; Biocompatible Materials/chemistry ; Extracellular Matrix/chemistry ; Humans ; Regenerative Medicine/methods ; Stem Cells/cytology ; Tissue Engineering/methods ; Tissue Scaffolds
Chemical Substances	Biocompatible Materials
Language	English
Publishing date	2013-07-05
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2649576-4
ISSN	2192-2659 ; 2192-2640
ISSN (online)	2192-2659
ISSN	2192-2640
DOI	10.1002/adhm.201300063
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Article ; Online: Minocycline modulates NFκB phosphorylation and enhances antimicrobial activity against Staphylococcus aureus in mesenchymal stromal/stem cells.

Guerra, Alberto Daniel / Rose, Warren E / Hematti, Peiman / Kao, W John

Stem cell research & therapy

2017 Volume 8, Issue 1, Page(s) 171

Abstract: Background: Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties due to their anti-inflammatory, angiogenic, and even antibacterial properties. We have shown previously that minocycline enhances the wound healing phenotype of ... ...

Abstract	Background: Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties due to their anti-inflammatory, angiogenic, and even antibacterial properties. We have shown previously that minocycline enhances the wound healing phenotype of MSCs, and MSCs encapsulated in poly(ethylene glycol) and gelatin-based hydrogels with minocycline have antibacterial properties against Staphylococcus aureus (SA). Here, we investigated the signaling pathway that minocycline modulates in MSCs which results in their enhanced wound healing phenotype and determined whether preconditioning MSCs with minocycline has an effect on antimicrobial activity. We further investigated the in-vivo antimicrobial efficacy of MSC and antibiotic-loaded hydrogels in inoculated full-thickness cutaneous wounds. Methods: Modulation of cell signaling pathways in MSCs with minocycline was analyzed via western blot, immunofluorescence, and ELISA. Antimicrobial efficacy of MSCs pretreated with minocycline was determined by direct and transwell coculture with SA. MSC viability after SA coculture was determined via a LIVE/DEAD® stain. Internalization of SA by MSCs pretreated with minocycline was determined via confocal imaging. All protein and cytokine analysis was done via ELISA. The in-vivo antimicrobial efficacy of MSC and antibiotic-loaded hydrogels was determined in Sprague-Dawley rats inoculated with SA. Two-way ANOVA for multiple comparisons was used with Bonferroni test assessment and an unpaired two-tailed Student's t test was used to determine p values for all assays with multiple or two conditions, respectively. Results: Minocycline leads to the phosphorylation of transcriptional nuclear factor-κB (NFκB), but not c-Jun NH Conclusions: Minocycline modulates the NFκB pathway in MSCs that leads to an enhanced production of IL-6 and internalization of SA. This mechanism may have contributed to the in-vivo antibacterial efficacy of MSC and antibiotic-loaded hydrogels.
MeSH term(s)	Adult ; Cells, Immobilized/immunology ; Female ; Humans ; Male ; Mesenchymal Stromal Cells/immunology ; Minocycline/pharmacology ; NF-kappa B/immunology ; Phosphorylation/drug effects ; Phosphorylation/immunology ; Staphylococcus aureus/immunology
Chemical Substances	NF-kappa B ; Minocycline (FYY3R43WGO)
Language	English
Publishing date	2017--21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-017-0623-1
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Article ; Online: Minocycline enhances the mesenchymal stromal/stem cell pro-healing phenotype in triple antimicrobial-loaded hydrogels.

Guerra, Alberto Daniel / Rose, Warren E / Hematti, Peiman / Kao, W John

Acta biomaterialia

2017 Volume 51, Page(s) 184–196

Abstract: Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties including an anti-inflammatory cytokine profile and the promotion of angiogenesis via expression of growth factors in pre-clinical models. MSCs encapsulated in poly(ethylene ... ...

Abstract	Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties including an anti-inflammatory cytokine profile and the promotion of angiogenesis via expression of growth factors in pre-clinical models. MSCs encapsulated in poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) crosslinked hydrogels have led to controlled cellular presentation at wound sites with favorable wound healing outcomes. However, the therapeutic potential of MSC-loaded hydrogels may be limited by non-specific protein adsorption on the delivery matrix that could facilitate the initial adhesion of microorganisms and subsequent virulent biofilm formation. Antimicrobials loaded concurrently in the hydrogels with MSCs could reduce microbial bioburden and promote healing, but the antimicrobial effect on the MSC wound healing capacity and the antibacterial efficacy of the hydrogels is unknown. We demonstrate that minocycline specifically induces a favorable change in MSC migration capacity, proliferation, gene expression, extracellular matrix (ECM) attachment, and adhesion molecule and growth factor release with subsequent increased angiogenesis. We then demonstrate that hydrogels loaded with MSCs, minocycline, vancomycin, and linezolid can significantly decrease bacterial bioburden. Our study suggests that minocycline can serve as a dual mechanism for the regenerative capacity of MSCs and the reduction of bioburden in triple antimicrobial-loaded hydrogels. Statement of significance: Wound healing is a complex biological process that can be hindered by bacterial infection, excessive inflammation, and inadequate microvasculature. In this study, we develop a new formulation of poly(ethylene glycol) diacrylate and thiolated gelatin poly(ethylene glycol) crosslinked hydrogels loaded with minocycline, vancomycin, linezolid, and mesenchymal stromal/stem cells that induces a favorable wound healing phenotype in mesenchymal stromal/stem cells and prevents bacterial bioburden on the hydrogel. This combinatorial approach to biomaterial development has the potential to impact wound healing for contaminated full thickness cutaneous wounds.
MeSH term(s)	Adult ; Anti-Infective Agents/pharmacology ; Bacterial Adhesion/drug effects ; Cell Adhesion/drug effects ; Cell Survival/drug effects ; Human Umbilical Vein Endothelial Cells/drug effects ; Humans ; Hydrogels/pharmacology ; Immunomodulation/drug effects ; Intercellular Signaling Peptides and Proteins/pharmacology ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/drug effects ; Microbial Sensitivity Tests ; Minocycline/pharmacology ; Neovascularization, Physiologic/drug effects ; Phenotype ; Staphylococcus aureus/drug effects ; Staphylococcus aureus/growth & development ; Wound Healing/drug effects
Chemical Substances	Anti-Infective Agents ; Hydrogels ; Intercellular Signaling Peptides and Proteins ; Minocycline (FYY3R43WGO)
Language	English
Publishing date	2017-01-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2017.01.021
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Article ; Online: Poly(ethylene glycol)-containing hydrogels modulate α-defensin release from polymorphonuclear leukocytes and monocyte recruitment.

Lieberthal, Tyler Jacob / Cohen, Hannah Caitlin / Kao, W John

Journal of biomedical materials research. Part A

2015 Volume 103, Issue 12, Page(s) 3772–3780

Abstract: Polymorphonuclear leukocytes (PMNs) release granule proteins as the first line of defense against bacteria and set up chemotactic gradients that result in monocyte infiltration to the site of injury. Although well established, the role of biomaterials in ...

Abstract	Polymorphonuclear leukocytes (PMNs) release granule proteins as the first line of defense against bacteria and set up chemotactic gradients that result in monocyte infiltration to the site of injury. Although well established, the role of biomaterials in regulating adherent PMN degranulation and subsequent PMN-monocyte paracrine interactions is less clear. The aim of this study was to determine how biomaterials affect the degranulation of selected biomarkers and downstream monocyte adhesion and transendothelial migration. Poly(ethylene glycol) (PEG)-containing hydrogels (PEG and an interpenetrating network of PEG and gelatin) promote the release of the α-defensins human neutrophil peptides 1-3, but not azurocidin or monocyte chemotactic protein-1. Although human neutrophil peptides 1-3 are monocyte chemoattractants, no subsequent effects on monocyte transmigration are observed in static conditions. Under flow conditions, monocyte adhesion on human umbilical vein endothelial cells stimulated with tumor necrosis factor-α is elevated in the presence of granule proteins from PMNs adherent on polydimethylsiloxane, but not from PMNs cultured on PEG hydrogels. These results suggest that PEG promotes PMN antimicrobial capacity without enhanced monocyte recruitment.
MeSH term(s)	Biocompatible Materials/metabolism ; Cell Adhesion ; Cell Degranulation ; Cells, Cultured ; Chemotaxis, Leukocyte ; Human Umbilical Vein Endothelial Cells ; Humans ; Hydrogels/metabolism ; Monocytes/cytology ; Monocytes/metabolism ; Neutrophils/cytology ; Neutrophils/metabolism ; Polyethylene Glycols/metabolism ; alpha-Defensins/metabolism
Chemical Substances	Biocompatible Materials ; Hydrogels ; alpha-Defensins ; Polyethylene Glycols (30IQX730WE)
Language	English
Publishing date	2015-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2099989-6
ISSN	1552-4965 ; 1549-3296 ; 0021-9304
ISSN (online)	1552-4965
ISSN	1549-3296 ; 0021-9304
DOI	10.1002/jbm.a.35519
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Book ; Conference proceedings: Biomaterials: the enabling technology

Kao, W. John

: Society for Biomaterials 2006 annual meeting, April 26 - 29, 2006, David L. Lawrence Convention Center, Pittsburg, Pennsylvania, USA; transactions of the 31st annual meeting

(Transactions / Society for Biomaterials ; 29)

2006

Event/congress	Annual meeting. Society for Biomaterials (31, 2006.04.26-29, PittsburghPa.)
Author's details	[W. John Kao, program chair]
Series title	Transactions / Society for Biomaterials ; 29
Language	English
Size	S. 365-719
Publisher	Society for Biomaterials
Publishing place	Mount Laurel, NJ
Document type	Book ; Conference proceedings
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Book ; Conference proceedings: Biomaterials: the enabling technology

Kao, W. John

: Society for Biomaterials 2006 annual meeting, April 26 - 29, 2006, David L. Lawrence Convention Center, Pittsburg, Pennsylvania, USA; transactions of the 31st annual meeting

(Transactions / Society for Biomaterials ; 29)

2006

Event/congress	Annual meeting. Society for Biomaterials (31, 2006.04.26-29, PittsburghPa.)
Author's details	[W. John Kao, program chair]
Series title	Transactions / Society for Biomaterials ; 29
Language	English
Size	LVIII, 444 S
Publisher	Society for Biomaterials
Publishing place	Mount Laurel, NJ
Document type	Book ; Conference proceedings
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Book ; Conference proceedings: Biomaterials: the enabling technology

Kao, W. John

Society for Biomaterials 2006 annual meeting, April 26 - 29, 2006, David L. Lawrence Convention Center, Pittsburg, Pennsylvania, USA ; transactions of the 31st annual meeting

(Transactions / Society for Biomaterials ; 29)

2006

Event/congress	Annual meeting. Society for Biomaterials (31, 2006.04.26-29, PittsburghPa.)
Author's details	[W. John Kao, program chair]
Series title	Transactions / Society for Biomaterials ; 29
Language	English
Publisher	Society for Biomaterials
Publishing place	Mount Laurel, NJ
Document type	Book ; Conference proceedings
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article: Emulsion Cross-Linking Technique for Human Fibroblast Encapsulation.

Chaemsawang, Watcharaphong / Prasongchean, Weerapong / Papadopoulos, Konstantinos I / Sukrong, Suchada / Kao, W John / Wattanaarsakit, Phanphen

International journal of biomaterials

2018 Volume 2018, Page(s) 9317878

Abstract: Microencapsulation with biodegradable polymers has potential application in drug and cell delivery systems and is currently used in probiotic delivery. In the present study, microcapsules of human fibroblast cells (CRL2522) were prepared by emulsion ... ...

Abstract	Microencapsulation with biodegradable polymers has potential application in drug and cell delivery systems and is currently used in probiotic delivery. In the present study, microcapsules of human fibroblast cells (CRL2522) were prepared by emulsion cross-linking technique. Tween 80 surfactant at a 2% concentration through phase inversion resulted in the most efficient and stable size, morphology, and the cells survival at least 50% on day 14. Emulsion cross-linking microcapsule preparation resulted in smaller and possibly more diverse particles that can be developed clinically to deliver encapsulated mammalian cells for future disease treatments.
Language	English
Publishing date	2018-07-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2494344-7
ISSN	1687-8795 ; 1687-8787
ISSN (online)	1687-8795
ISSN	1687-8787
DOI	10.1155/2018/9317878
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Article ; Online: Poly(ethylene glycol)-containing hydrogels promote the release of primary granules from human blood-derived polymorphonuclear leukocytes.

Cohen, Hannah Caitlin / Lieberthal, Tyler Jacob / Kao, W John

Journal of biomedical materials research. Part A

2014 Volume 102, Issue 12, Page(s) 4252–4261

Abstract: Polymorphonuclear leukocytes (PMNs) are recruited to sites of injury and biomaterial implants. Once activated, PMNs can exocytose their granule subsets to recruit monocytes (MCs) and mediate MC/macrophage activation. We investigated the release of ... ...

Abstract	Polymorphonuclear leukocytes (PMNs) are recruited to sites of injury and biomaterial implants. Once activated, PMNs can exocytose their granule subsets to recruit monocytes (MCs) and mediate MC/macrophage activation. We investigated the release of myeloperoxidase (MPO), a primary granule marker, and matrix metalloproteinase-9 (MMP-9), a tertiary granule marker, from human blood-derived PMNs cultured on poly(ethylene glycol) (PEG) hydrogels, polydimethylsiloxane (PDMS), tissue culture polystyrene (TCPS) and gelatin-PEG (GP) hydrogels, with and without the presence of the bacterial peptide formyl-Met-Leu-Phe. Supernatants from PMN cultures on PEG-containing hydrogels (i.e., PEG and GP hydrogels) had higher concentrations of MPO than those from PMN cultures on PDMS or TCPS at 2 h. PMNs on all biomaterials released comparable levels of MMP-9 at 2 h, indicating that PMNs cultured on PEG-containing hydrogels have different mechanisms of release for primary and tertiary granules. Src family kinases were involved in the release of MPO from PMNs cultured on PEG hydrogels, TCPS and GP hydrogels and in the release of MMP-9 from PMNs cultured on all four biomaterials. The increased release of primary granules from PMNs on PEG-containing hydrogels did not significantly increase MC chemotaxis, indicating that additional co-effectors in the dynamic inflammatory milieu in vivo modulate PMN-mediated MC recruitment.
MeSH term(s)	Chemotaxis ; Culture Media, Conditioned/chemistry ; Humans ; Hydrogels/chemistry ; Macrophage Activation/drug effects ; Macrophages/cytology ; Macrophages/metabolism ; Matrix Metalloproteinase 9/chemistry ; Monocytes/cytology ; Monocytes/metabolism ; N-Formylmethionine Leucyl-Phenylalanine/pharmacology ; Neutrophils/cytology ; Neutrophils/metabolism ; Polyethylene Glycols/chemistry ; Secretory Vesicles/chemistry
Chemical Substances	Culture Media, Conditioned ; Hydrogels ; Polyethylene Glycols (3WJQ0SDW1A) ; N-Formylmethionine Leucyl-Phenylalanine (59880-97-6) ; MMP9 protein, human (EC 3.4.24.35) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
Language	English
Publishing date	2014-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2099989-6
ISSN	1552-4965 ; 1549-3296 ; 0021-9304
ISSN (online)	1552-4965
ISSN	1549-3296 ; 0021-9304
DOI	10.1002/jbm.a.35101
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