| 1. |
- Fan, Yanmiao, et al.
(författare)
-
Dendritic Hydrogels Induce Immune Modulation in Human Keratinocytes and Effectively Eradicate Bacterial Pathogens
- 2021
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 143:41, s. 17180-17190
-
Tidskriftsartikel (refereegranskat)abstract
- Infections caused by antibiotic-resistant bacteria are globally a major threat, leading to high mortality rates and increased economic burden. Novel treatment strategies are therefore urgently needed by healthcare providers to protect people. Biomaterials that have inherent antibacterial properties and do not require the use of antibiotics present an attractive and feasible avenue to achieve this goal. Herein, we demonstrate the effect of a new class of cationic hydrogels based on amino-functional hyperbranched dendritic-linear-dendritic copolymers (HBDLDs) exhibiting excellent antimicrobial activity toward a wide range of clinical Gram-positive and Gram-negative bacteria, including drug-resistant strains isolated from wounds. Intriguingly, the hydrogels can induce the expression of the antimicrobial peptides RNase 7 and psoriasin, promoting host-mediated bacterial killing in human keratinocytes (HaCaT). Moreover, treatment with the hydrogels decreased the proinflammatory cytokine IL-1 beta, reactive nitrogen species (NO), and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells, conjunctively resulting in reduced inflammation.
|
|
| 2. |
- Fan, Yanmiao, et al.
(författare)
-
Nanogel encapsulated hydrogels as advanced wound dressings for the controlled delivery of antibiotics
- 2021
-
Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 31
-
Tidskriftsartikel (refereegranskat)abstract
- Biocompatible and degradable dual-delivery gel systems based on hyperbrancheddendritic−linear−dendritic copolymers (HBDLDs) is herein conceptualizedand accomplished via thiol-ene click chemistry. The elasticity of thehydrogels is tunable by varying the lengths of PEG (2, 6, 10 kDa) or the dryweight percentages (20, 30, 40 wt%), and are found to be between 2–14.7 kPa,comparable to human skin. The co-delivery of antibiotics is achieved, wherethe hydrophilic drug novobiocin sodium salt (NB) is entrapped within thehydrophilic hydrogel, while the hydrophobic antibiotic ciprofloxacin (CIP) isencapsulated within the dendritic nanogels (DNGs) with hydrophobic cores(DNGs-CIP). The DNGs-CIP with drug loading capacity of 2.83 wt% are thenphysically entrapped within the hybrid hydrogels through UV curing. Thehybrid hydrogels enabled the quick release of NB and prolonged released ofCIP. In vitro cell infection assays showed that the antibiotic-loaded hybridhydrogels are able to treat bacterial infections with significant bacterialreduction. Hybrid hydrogel band aids are fabricated and exhibited betterantibacterial activity compared with commercial antimicrobial band aids.Remarkably, most hydrogels and hybrid hydrogels showed enhanced humandermal cell proliferation and could be degraded into non-toxic constituents,showing great promise as wound dressing materials.
|
|
| 3. |
- Fan, Yanmiao, et al.
(författare)
-
Scalable Dendritic Hydrogels Targeting Drug-Resistant Skin Pathogens and the Immunomodulation Activity in Keratinocytes
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Microbial infections caused by antibiotic-resistant bacteria are a major threat to humans, associated with a high mortality and for the society increased economic burden. To address this, a series of cationic hydrogels based on amino-functional hyperbranched dendritic−linear−dendritic copolymers (HBDLDs) were formed easily within 1 min through interactions between the amino-terminated HBDLDs and di(N-hydroxysuccinimide ester) functionalized polyethylene glycol (PEG). The hydrogels exhibited excellent inherent antimicrobial activity towards a wide range of Gram-positive and Gram-negative clinical bacteria including drug-resistant strains, isolated from wounds. In vitro cell infection assays showed that the hydrogels were able to significantly reduce cell infections caused by different strains, with the highest killing efficacy of 96% towards S. aureus. The hydrogels also inhibited the initiation of E. coli biofilm formation. Remarkably, the hydrogels induced the expression of the antimicrobial peptides, RNase 7 and psoriasin, in keratinocytes (HaCaT) which suggests that the hydrogels are likely able to promote host-mediated bacterial killing. The expression of pro-inflammatory cytokine IL-1β, reactive nitrogen species (NO) and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells were reduced after the treatment with the hydrogels. The hydrogels degraded within 24 h, showing great promise for treating skin infections and reducing inflammation.
|
|
| 4. |
- Fortuin-de Smidt, Melony C., et al.
(författare)
-
Effect of exercise training on insulin sensitivity, hyperinsulinemia and ectopic fat in black South African women : a randomized controlled trial
- 2020
-
Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 183:1, s. 51-61
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: We investigated the effects of a 12-week exercise intervention on insulin sensitivity (SI) and hyperinsulinemia and associated changes in regional and ectopic fat.Research design and methods: Healthy, black South African women with obesity (mean age 23 ± 3.5 years) and of isiXhosa ancestry were randomised into a 12-week aerobic and resistance exercise training group (n = 23) and a no exercise group (control, n = 22). Pre and post-intervention testing included assessment of SI, insulin response to glucose (AIRg), insulin secretion rate (ISR), hepatic insulin extraction (FEL) and disposition index (DI) (AIRg × SI) (frequently sampled i.v. glucose tolerance test); fat mass and regional adiposity (dual-energy X-ray absorptiometry); hepatic, pancreatic and skeletal muscle fat content and abdominal s.c. and visceral adipose tissue volumes (MRI).Results: Exercise training increased VO2peak (mean ± s.d.: 24.9 ± 2.42 to 27.6 ± 3.39 mL/kg/min, P < 0.001), SI (2.0 (1.2–2.8) to 2.2 (1.5–3.7) (mU/l)−1 min−1, P = 0.005) and DI (median (interquartile range): 6.1 (3.6–7.1) to 6.5 (5.6–9.2) × 103 arbitrary units, P = 0.028), and decreased gynoid fat mass (18.5 ± 1.7 to 18.2 ± 1.6%, P < 0.001) and body weight (84.1 ± 8.7 to 83.3 ± .9.7 kg, P = 0.038). None of these changes were observed in the control group, but body weight increased (P = 0.030). AIRg, ISR and FEL, VAT, SAT and ectopic fat were unaltered after exercise training. The increase in SI and DI were not associated with changes in regional or ectopic fat.Conclusion: Exercise training increased SI independent from changes in hyperinsulinemia and ectopic fat, suggesting that ectopic fat might not be a principal determinant of insulin resistance in this cohort.
|
|
| 5. |
- Goedecke, Julia H., et al.
(författare)
-
An Exercise Intervention to Unravel the Mechanisms Underlying Insulin Resistance in a Cohort of Black South African Women : Protocol for a Randomized Controlled Trial and Baseline Characteristics of Participants
- 2018
-
Ingår i: JMIR Research Protocols. - : JMIR PUBLICATIONS, INC. - 1929-0748. ; 7:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The pathogenesis of type 2 diabetes (T2D) in black African women is complex and differs from that in their white counterparts. However, earlier studies have been cross-sectional and provide little insight into the causal pathways. Exercise training is consistently used as a model to examine the mechanisms underlying insulin resistance and risk for T2D.Objective: The objective of the study was to examine the mechanisms underlying the changes in insulin sensitivity and secretion in response to a 12-week exercise intervention in obese black South African (SA) women.Methods: A total of 45 obese (body mass index, BMI: 30-40 kg/m2) black SA women were randomized into a control (n=22) or experimental (exercise; n=23) group. The exercise group completed 12 weeks of supervised combined aerobic and resistance training (40-60 min, 4 days/week), while the control group maintained their typical physical activity patterns, and both groups were requested not to change their dietary patterns. Before and following the 12-week intervention period, insulin sensitivity and secretion (frequently sampled intravenous glucose tolerance test) and its primary and secondary determinants were measured. Dietary intake, sleep quality and quantity, physical activity, and sedentary behaviors were measured every 4 weeks.Results: The final sample included 20 exercise and 15 control participants. Baseline sociodemographics, cardiorespiratory fitness, anthropometry, cardiometabolic risk factors, physical activity, and diet did not differ between the groups (P>.05).Conclusions: The study describes a research protocol for an exercise intervention to understand the mechanisms underlying insulin sensitivity and secretion in obese black SA women and aims to identify causal pathways underlying the high prevalence of insulin resistance and risk for T2D in black SA women, targeting specific areas for therapeutic intervention.
|
|
| 6. |
- Lüchow, Mads, et al.
(författare)
-
Modular, synthetic, thiol-ene mediated hydrogel networks as potential scaffolds for 3D cell cultures and tissue regeneration
- 2020
-
Ingår i: Journal of Polymer Science. - : John Wiley and Sons Inc. - 2642-4150 .- 2642-4169. ; 58:22, s. 3153-3164
-
Tidskriftsartikel (refereegranskat)abstract
- Natural polymers such as collagen are popular materials for tissue engineering scaffolds due to their innate bioactivity and biocompatibility. Being derived from animal sources, however, means that batch-to-batch consistency is often low and the extraction of collagen is costly. This conundrum facilitates the need for synthetic alternatives as scaffolding materials. In this study, a system of poly(ethylene glycol) (PEG)-based thiol-ene coupled (TEC) hydrogel scaffolds is presented for tissue engineering purposes. The platform includes several necessary features, namely cytocompatibility, high swelling ability, biodegradability, tunable stiffness, and fast, straightforward fabrication. The swelling ability is provided by the hydrophilicity of the ether-links of PEG, which facilitated the formation of high water content hydrogels that match the water content of soft tissues for the proper diffusion of nutrients and waste compounds. TEC ensures fast and facile fabrication, with cross-linking moieties that allow for the biodegradation of the hydrogel network through hydrolytic cleavage. The mechanical properties of the scaffolds are made tunable in the range of storage moduli spanning <1 kPa to >100 kPa. It is also shown that despite the synthetic nature of the hydrogels, human dermal fibroblasts and murine macrophages, Raw 264.7, were able to survive and produce extracellular protein excretions while embedded in the 3D hydrogels.
|
|
| 7. |
- Zhang, Yuning, et al.
(författare)
-
Degradable High Molecular Weight Monodisperse Dendritic Poly(ethylene glycols)
- 2020
-
Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 21:10, s. 4294-4301
-
Tidskriftsartikel (refereegranskat)abstract
- Poly(ethylene glycols) (PEGs) are extensively explored by the pharma industry as foundations for new therapeutic products. PEGs are typically used for their conjugation to active drugs, peptides, and proteins and the likeliness to increase the half-life and enhance the therapeutic outcome. Considering the necessity of batch-to-batch consistency for clinical products, monodisperse PEGs are highly attractive but are generally limited to 5 kDa as an upper molecular weight (Mw) and with an oligomer purity of 95%. By amalgamating short, monodisperse PEGs with dendritic frameworks based on 2,2-bis(methylol)propionic acid polyesters, we showcase a robust synthetic approach to monodisperse PEGs with Mw ranging from 2 to 65 kDa. The latter is, to our knowledge, the highest Mw structure of its kind ever reported. Importantly, the dendritic multifunctional connector facilitated degradability at pH 7.4 at 37 °C, which is an important feature for the delivery of therapeutic agents.
|
|
| 8. |
- Zhang, Yuning
(författare)
-
Novel Therapeutic Platform of Micelles and Nanogels from Dopa-Functionalized Triblock Copolymers
- 2021
-
Ingår i: Small. - : Wiley. - 1613-6829 .- 1613-6810. ; 17:17, s. 2007305-
-
Tidskriftsartikel (refereegranskat)abstract
- Multi-drug delivery systems constructed from a basic polymeric scaold, and which have the ability to target a variety of biomedical applications, can streamline the development of nanomedicine to provide both environmental and economical relief. Herein, amphiphilic ABA-triblock copolymers are synthesized and assembled sequentially into micelles and nanogels as drug delivery systems following a thorough evaluation on advanced in vitro models to explore their potential for the treatment of cancer and bacterial infections. Short blocks of -methyl--allyloxycarbonyl-,-dioxan--one (MAC) are oli-gomerized from PEGk and thereafter functionalized with dihydroxyphenyla-lanine (dopa)-functional thiols using thiol-ene coupling (TEC) click chemistry. The copolymers self-assemble into well-defined micelles in aqueous solution and are further formulated into nanogels via UV-induced TEC. The resulting spherical micelles and nanogels are stable nanoparticles, with sizes ranging between and nm. The nanogels are found to be non-toxic to a panel of cell lines and mask the toxicity of the potent drugs until their release. The nanogels would be superior to micelles for the elimination of cancer cells supported by both D cell culture and a D spheroid model. The opposite conclusion could be drawn for bacteria inhibition.
|
|
