Browsing by Subject "DELIVERY"

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  • Luchkina, Natalia V.; Huupponen, Johanna; Clarke, Vernon R. J.; Coleman, Sarah K.; Keinanen, Kari; Taira, Tomi; Lauri, Sari E. (2014)
  • Ruusuvuori, Johanna; Aaltonen, Tarja; Lonka, Eila; Salmenlinna, Inkeri; Laakso, Minna (2020)
    The quality of interaction between hearing health professionals and patients is one prominent, yet under-studied explanation for the low adherence in acquiring and using a hearing aid. This study describes two different ways of introducing hearing aid to the patients at their first visits at the hearing clinic: an inquiry asking patients opinion followed by offer, and an expert evaluation of the necessity of a hearing aid; and shows two different trajectories ensuing from these introductions. The trajectories represent two extreme ends of a continuum of practices of starting a discussion about hearing aid rehabilitation, in terms of how these practices affect patient participation in decision-making. The analysis shows how granting different degrees of deontic and epistemic rights to professionals and patients has different consequences with regard to the activity of reaching shared understanding on the treatment. The data consist of 17 video-recorded encounters at the hearing clinic. The method used is conversation analysis.
  • Heilkkinen, Emma M.; Auriola, Seppo; Ranta, Veli-Pekka; Demarais, Nicholas J.; Grey, Angus C.; del Amo, Eva M.; Toropainen, Elisa; Vellonen, Kati-Sisko; Urtti, Arto; Ruponen, Marika (2019)
    Lens is the avascular tissue in the eye between the aqueous humor and vitreous. Drug binding to the lens might affect ocular pharmacokinetics, and the binding may also have a pharmacological role in drug-induced cataract and cataract treatment. Drug distribution in the lens has been studied in vitro with many compounds; however, the experimental methods vary, no detailed information on distribution between the lens sublayers exist, and the partition coefficients are reported rarely. Therefore, our objectives were to clarify drug localization in the lens layers and establish partition coefficients for a wide range of molecules. Furthermore, we aimed to illustrate the effect of lenticular drug binding on overall ocular drug pharmacokinetics. We studied the distribution of 16 drugs and three fluorescent dyes in whole porcine lenses in vitro with imaging mass spectrometry and fluorescence microscopy techniques. Furthermore, we determined lens/buffer partition coefficients with the same experimental setup for 28 drugs with mass spectrometry. Finally, the effect of lenticular binding of drugs on aqueous humor drug exposure was explored with pharmacokinetic simulations. After 4 h, the drugs and the dyes distributed only to the outermost lens layers (capsule and cortex). The lens/buffer partition coefficients for the drugs were low, ranging from 0.05 to 0.8. On the basis of the pharmacokinetic simulations, a high lens-aqueous humor partition coefficient increases drug exposure in the lens but does not significantly alter the pharmacokinetics in the aqueous humor. To conclude, the lens seems to act mainly as a physical barrier for drug distribution in the eye, and drug binding to the lens affects mainly the drug pharmacokinetics in the lens.
  • Gabrysch, Sabine; Nesbitt, Robin C.; Schoeps, Anja; Hurt, Lisa; Soremekun, Seyi; Edmond, Karen; Manu, Alexander; Lohela, Terhi J.; Danso, Samuel; Tomlin, Keith; Kirkwood, Betty; Campbell, Oona M. R. (2019)
    Background Maternal and perinatal mortality are still unacceptably high in many countries despite steep increases in facility birth. The evidence that childbirth in facilities reduces mortality is weak, mainly because of the scarcity of robust study designs and data. We aimed to assess this link by quantifying the influence of major determinants of facility birth (cluster-level facility birth, wealth, education, and distance to childbirth care) on several mortality outcomes, while also considering quality of care. Methods Our study is a secondary analysis of surveillance data on 119 244 pregnancies from two large population-based cluster-randomised controlled trials in Brong Ahafo, Ghana. In addition, we specifically collected data to assess quality of care at all 64 childbirth facilities in the study area. Outcomes were direct maternal mortality, perinatal mortality, first-day and early neonatal mortality, and antepartum and intrapartum stillbirth. We calculated cluster-level facility birth as the percentage of facility births in a woman's village over the preceding 2 years, and we computed distances from women's regular residence to health facilities in a geospatial database. Associations between determinants of facility birth and mortality outcomes were assessed in crude and multivariable multilevel logistic regression models. We stratified perinatal mortality effects by three policy periods, using April 1, 2005, and July 1, 2008, as cutoff points, when delivery-fee exemption and free health insurance were introduced in Ghana. These policies increased facility birth and potentially reduced quality of care. Findings Higher proportions of facility births in a cluster were not linked to reductions in any of the mortality outcomes. In women who were wealthier, facility births were much more common than in those who were poorer, but mortality was not lower among them or their babies. Women with higher education had lower mortality risks than less-educated women, except first-day and early neonatal mortality. A substantially higher proportion of women living in areas closer to childbirth facilities had facility births and caesarean sections than women living further from childbirth facilities, but mortality risks were not lower despite this increased service use. Among women who lived in areas closer to facilities offering comprehensive emergency obstetric care (CEmOC), emergency newborn care, or high-quality routine care, or to facilities that had providers with satisfactory competence, we found a lower risk of intrapartum stillbirth (14.2 per 1000 deliveries at >20 km from a CEmOC facility vs 10.4 per 1000 deliveries at Interpretation Facility birth does not necessarily convey a survival benefit for women or babies and should only be recommended in facilities capable of providing emergency obstetric and newborn care and capable of safeguarding uncomplicated births. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
  • Torrieri, Giulia; Fontana, Flavia; Figueiredo, Patricia; Liu, Zehua; Almeida Ferreira, Monica; Talman, Virpi; Martins, João Pedro; Fusciello, Manlio; Moslova, Karina; Teesalu, Tambet; Cerullo, Vincenzo; Hirvonen, Jouni; Ruskoaho, Heikki; Balasubramanian, Vimalkumar; Santos, Hélder A. (2020)
    The advent of nanomedicine has recently started to innovate the treatment of cardiovascular diseases, in particular myocardial infarction. Although current approaches are very promising, there is still an urgent need for advanced targeting strategies. In this work, the exploitation of macrophage recruitment is proposed as a novel and synergistic approach to improve the addressability of the infarcted myocardium achieved by current peptide-based heart targeting strategies. For this purpose, an acetalated dextran-based nanosystem is designed and successfully functionalized with two different peptides, atrial natriuretic peptide (ANP) and linTT1, which target, respectively, cardiac cells and macrophages associated with atherosclerotic plaques. The biocompatibility of the nanocarrier is screened on both macrophage cell lines and primary macrophages, showing high safety, in particular after functionalization of the nanoparticles' surface. Furthermore, the system shows higher association versus uptake ratio towards M2-like macrophages (approximately 2-fold and 6-fold increase in murine and human primary M2-like macrophages, respectively, compared to M1-like). Overall, the results demonstrate that the nanosystem has potential to exploit the "hitchhike" effect on M2-like macrophages and potentially improve, in a dual targeting strategy, the ability of the ANP peptide to target infarcted heart.
  • Ni, Qianqian; Cheng, Guizhi; Chen, An; Heinonen, Seppo (2020)
    Background The mental health of pregnant women, particularly those with elevated risks, has been an issue of global concern. Thus far, few studies have addressed the mental health of pregnant women with threatened preterm labour (TPL). This study investigated the prevalence of self-perceived burden (SPB) among Chinese women hospitalized due to TPL during pregnancy and early postpartum depressive disorders, exploring the effect of SPB and other potential risk factors on the early signs of postpartum depressive disorders. Methods A self-reported survey was conducted in the obstetrics department of Anhui Provincial Hospital, China. Women hospitalized with TPL were approached 1 week after delivery. One hundred fifty women were recruited from January 2017 to December 2017. The Self-Perceived Burden Scale (SPBS) and Edinburgh Postnatal Depression Scale (EPDS) were the main measures. Descriptive statistics, Spearman correlations, and a multiple logistic regression were employed for data analysis. Results SPB and early postpartum depressive disorders were commonly experienced by Chinese women hospitalized with TPL, and SPB was positively and significantly correlated with depressive symptoms. A multiple logistic regression analysis revealed that for the women hospitalized with TPL during pregnancy, the emotional aspect of SPB (OR = 1.42, 95% CI = 1.11-1.83, p = 0.006), age (OR = 1.14, 95% CI = 1.02-1.27, p = 0.023), occupation (OR = 3.48, 95% CI = 1.18-10.20, p = 0.023), the history of scarred uterus (OR = 7.96, 95% CI = 1.49-42.48, p = 0.015), the delivery mode of the present birth (OR = 6.19, 95% CI = 1.72-22.30, p = 0.005), and family support during pregnancy (OR = 0.60, 95% CI = 0.45-0.82, p = 0.001) were significant factors predicting early postpartum depressive symptoms. Conclusion This study indicates that SPB and early postpartum depressive disorders are prevalent mental issues among Chinese women hospitalized with TPL, and that SPB, especially perceived emotional burden, is a strong predictor of early postpartum depressive disorders. Our study suggests the necessity of paying attention to mental health issues, e.g. SPB and postpartum depressive symptoms among hospitalized women with TPL, and providing appropriate interventions at the prenatal stage to prevent adverse consequences.
  • Badazhkova, Veronika D.; Raik, Sergei; Polyakov, Dmitry S.; Poshina, Daria N.; Skorik, Yury A. (2020)
    Recently, much effort has been expended on the development of non-viral gene delivery systems based on polyplexes of nucleic acids with various cationic polymers. Natural polysaccharide derivatives are promising carriers due to their low toxicity. In this work, chitosan was chemically modified by a reaction with 4-formyl-n,n,n-trimethylanilinium iodide and pyridoxal hydrochloride and subsequent reduction of the imine bond with NaBH4. This reaction yielded three novel derivatives, n-[4-(n',n',n'-trimethylammonium)benzyl]chitosan chloride (TMAB-CS), n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (Pyr-CS), and n-[4-(n',n',n''-trimethylammonium)benzyl]-n-[(3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridine)methyl]chitosan chloride (PyrTMAB-CS). Their structures and degrees of substitution were established by H-1 NMR spectroscopy as DS1 = 0.22 for TMAB-CS, DS2 = 0.28 for Pyr-CS, and DS1 = 0.21, DS2 = 0.22 for PyrTMAB-CS. Dynamic light scattering measurements revealed that the new polymers formed stable polyplexes with plasmid DNA encoding the green fluorescent protein (pEGFP-N3) and that the particles had the smallest size (110-165 nm) when the polymer:DNA mass ratio was higher than 5:1. Transfection experiments carried out in the HEK293 cell line using the polymer:DNA polyplexes demonstrated that Pyr-CS was a rather poor transfection agent at polymer:DNA mass ratios less than 10:1, but it was still more effective than the TMAB-CS and PyrTMAB-CS derivatives that contained a quaternary ammonium group. By contrast, TMAB-CS and PyrTMAB-CS were substantially more effective than Pyr-CS at higher polymer:DNA mass ratios and showed a maximum efficiency at 200:1 (50%-70% transfected cells). Overall, the results show the possibility of combining substituent effects in a single carrier, thereby increasing its efficacy.
  • Heiniö, Camilla; Sorsa, Suvi; Siurala, Mikko; Grönberg-Vähä-Koskela, Susanna; Havunen, Riikka; Haavisto, Elina; Koski, Anniina; Hemminki, Otto; Zafar, Sadia; Cervera-Carrascon, Victor; Munaro, Eleonora; Kanerva, Anna; Hemminki, Akseli (2019)
    After the discovery and characterization of the adenovirus in the 1950s, this prevalent cause of the common cold and other usually mild diseases has been modified and utilized in biomedicine in several ways. To date, adenoviruses are the most frequently used vectors and therapeutic (e.g., oncolytic) agents with a number of beneficial features. They infect both dividing and nondividing cells, enable high-level, transient protein expression, and are easy to amplify to high concentrations. As an important and versatile research tool, it is of essence to understand the limits and advantages that genetic modification of adenovirus vectors may entail. Therefore, a retrospective analysis was performed of adenoviral gene therapy constructs produced in the same laboratory with similar methods. The aim was to assess the impact of various modifications on the physical and functional titer of the virus. It was found that genome size (designed within "the 105% golden rule") did not significantly affect the physical titer of the adenovirus preparations, regardless of the type of transgene (e.g., immunostimulatory vs. other), number of engineered changes, and size of the mutated virus genome. One statistically significant exception was noted, however. Chimeric adenoviruses (5/3) had a slightly lower physical titer compared to Ad5-based viruses, although a trend for the opposite was true for functional titers. Thus, 5/3 chimeric viruses may in fact be appealing from a safety versus efficacy viewpoint. Armed viruses had lower functional and physical titers than unarmed viruses, while five genomic modifications started to decrease functional titer. Importantly, even highly modified armed viruses generally had good titers compatible with clinical testing. In summary, this paper shows the plasticity of adenovirus for various vector, oncolytic, and armed oncolytic uses. These results inform future generations of adenovirus-based drugs for human use. This information is directly transferable to academic laboratories and the biomedical industry involved in vector design and production optimization.
  • Wilkosz, Natalia; Rissanen, Sami; Cyza, Malgorzata; Szybka, Renata; Nowakowska, Maria; Bunker, Alex; Rog, Tomasz; Kepczynski, Mariusz (2017)
    Uptake of piroxicam, a non-steroidal anti-inflammatory drug, from the intestines after oral intake is limited due to its low solubility and its wide use is associated with several side effects related to the gastrointestinal tract. In this study, all-atom molecular dynamics (MD) simulations and fluorescent spectroscopy were employed to investigate the interaction of piroxicam in neutral, zwitterionic, and cationic forms with lipid bilayers composed of phosphatidylcholine, cholesterol, and PEGylated lipids. Our study was aimed to assess the potential for encapsulation of piroxicam in liposomal carriers and to shed more light on the process of gastrointestinal tract injury by the drug. Through both the MD simulations and laser scanning confocal microscopy, we have demonstrated that all forms of piroxicam can associate with the lipid bilayers and locate close to the water-membrane interface. Conventional liposomes used in drug delivery are usually stabilized by the addition of cholesterol and have their bloodstream lifetime extended through the inclusion of PEGylated lipids in the formulation to create a protective polymer corona. For this reason, we tested the effect of these two modifications on the behavior of piroxicam in the membrane. When the bilayer was PEGylated, piroxicam localize to the PEG layer and within the lipid headgroup region. This suggests that PEGylated liposomes are capable of carrying a larger quantity of piroxicam than the conventional ones. (C) 2017 Elsevier B.V. All rights reserved.
  • Ding, Yaping; Li, Wei; Correia, Alexandra; Yang, Yuyun; Zheng, Kai; Liu, Dongfei; Schubert, Dirk W.; Boccaccini, Aldo R.; Santos, Helder A.; Roether, Judith A. (2018)
    Electrospun hybrid scaffolds are an effective platform to deliver drugs site specifically for the prevention and treatment of diseases in addition to promote tissue regeneration because of the flexibility to load drugs therein. In the present study, electrospun hybrid scaffolds containing antibiotics were developed to support cellular activities and eliminate potential postoperative inflammation and infection. As a model drug, levofloxacin (LFX) was successfully incorporated into pure polyhydroxybutyrate/poly(epsilon-caprolactone) (PHB/PCL) scaffolds and PHB/PCL/sol-gel-derived silica (SGS) scaffolds. The influence of LFX on the morphology, mechanical performance, chemical structure, drug release profile, and antibacterial effect of the scaffolds was thoroughly and comparatively investigated. MG-63 osteoblast-like cell cultivation on both scaffolds certified that LFX inclusion did not impair the biocompatibility. In addition to the favorable cellular proliferation and differentiation, scaffolds containing both LFX and SGS displayed highly increased mineralization content. Therefore, the present multifunctional hybrid scaffolds are promising in tissue engineering applications.
  • van der Ark, Kees C. H.; Nugroho, Avis Dwi Wahyu; Berton-Carabin, Claire; Wang, Che; Belzer, Clara; de Vos, Willem M.; Schroen, Karin (2017)
    There is considerable attention for developing Akkermansia muciniphila as a new therapeutic microbe since it has shown to prevent diet-induced obesity and type 2 diabetes in mice. However, A. muciniphila is sensitive to gastric conditions such as low pH and oxygen. Therefore, we explored the possibility of encapsulating A. muciniphila in a water-in-oil-in-water (W/O/W) double emulsion, to allow for protection during gastric passage and subsequent release in the small intestine. The bacteria were efficiently encapsulated in the inner emulsion droplets and remained entrapped during in vitro gastric digestion. The cells were then released in the simulated intestinal phase of the in vitro system. The viability of encapsulated cells was found to be higher when compared to cells dispersed in buffer, that had been subjected to similar mechanical process as the one conducted to prepare the emulsion systems. Surprisingly, the viability of the processed cells was even higher than that of the cells dispersed in buffer without processing, likely due to shear-induced stress tolerance. To conclude, encapsulation in a double emulsion seems to be a. promising strategy to protect A. muciniphila during gastric passage in oral formulations.
  • Oliviero, Claudio; Heinonen, Mari; Valros, Anna; Peltoniemi, Olli (2010)
  • INOSS Int Network Obstetric Survey; Kallianidis, Athanasios F; Maraschini, Alice; Danis, Jakub; Jakobsson, Maija; Van Den Akker, Thomas (2020)
    Introduction Peripartum hysterectomy is a surgical procedure performed for severe obstetric complications such as major obstetric hemorrhage. The prevalence of peripartum hysterectomy in high-resource settings is relatively low. Hence, international comparisons and studying indications and associations with mode of birth rely on the use of national obstetric survey data. Objectives were to calculate the prevalence and indications of peripartum hysterectomy and its association with national cesarean section rates and mode of birth in nine European countries. Material and methods We performed a descriptive, multinational, population-based study among women who underwent peripartum hysterectomy. Data were collected from national or multiregional databases from nine countries participating in the International Network of Obstetric Survey Systems. We included hysterectomies performed from 22 gestational weeks up to 48 hours postpartum for obstetric hemorrhage, as this was the most restrictive, overlapping case definition between all countries. Main outcomes were prevalence and indications of peripartum hysterectomy. Additionally, we compared prevalence of peripartum hysterectomy between women giving birth vaginally and by cesarean section, and between women giving birth with and without previous cesarean section. Finally, we calculated correlation between prevalence of peripartum hysterectomy and national cesarean section rates, as well as national rates of women giving birth after a previous cesarean section. Results A total of 1302 peripartum hysterectomies were performed in 2 498 013 births, leading to a prevalence of 5.2 per 10 000 births ranging from 2.6 in Denmark to 10.7 in Italy. Main indications were uterine atony (35.3%) and abnormally invasive placenta (34.8%). Relative risk of hysterectomy after cesarean section compared with vaginal birth was 9.1 (95% CI 8.0-10.4). Relative risk for hysterectomy for birth after previous cesarean section compared with birth without previous cesarean section was 10.6 (95% CI 9.4-12.1). A strong correlation was observed between national cesarean section rate and prevalence of peripartum hysterectomy (rho = 0.67, P <.05). Conclusions Prevalence of peripartum hysterectomy may vary considerably between high-income countries. Uterine atony and abnormally invasive placenta are the commonest indications for hysterectomy. Birth by cesarean section and birth after previous cesarean section are associated with nine-fold increased risk of peripartum hysterectomy.
  • Yan, Yufei; Sun, Tao; Zhang, Hongbo; Ji, Xiuling; Sun, Yulong; Zhao, Xin; Deng, Lianfu; Qi, Jin; Cui, Wenguo; Almeida Santos, Helder; Zhang, Hongyu (2019)
    Osteoarthritis has been regarded as a typical lubrication deficiency related joint disease, which is characterized by the breakdown of articular cartilage at the joint surface and the inflammation of the joint capsule. Here, inspired by the structure of the fresh euryale ferox seed that possesses a slippery aril and a hard coat containing starchy kernel, a novel superlubricated nanoparticle, namely poly (3‐sulfopropyl methacrylate potassium salt)‐grafted mesoporous silica nanoparticles (MSNs‐NH2@PSPMK), is biomimicked and synthesized via a one‐step photopolymerization method. The nanoparticles are endowed with enhanced lubrication by the grafted PSPMK polyelectrolyte polymer due to the formation of tenacious hydration layers surrounding the negative charges, and simultaneously are featured with effective drug loading and release behavior as a result of the sufficient mesoporous channels in the MSNs. When encapsulated with an anti‐inflammatory drug diclofenac sodium (DS), the lubrication capability of the superlubricated nanoparticles is improved, while the drug release rate is sustained by increasing the thickness of PSPMK layer, which is simply achieved via adjustment of the precursor monomer concentration in the photopolymerization process. Additionally, the in vitro and in vivo experimental results show that the DS‐loaded MSNs‐NH2@PSPMK nanoparticles effectively protect the chondrocytes from degeneration, and thus, inhibit the development of osteoarthritis.
  • Känkänen, Voitto; Seitsonen, Jani; Tuovinen, Henri Mikael; Ruokolainen, Janne; Hirvonen, Jouni; Balasubramanian, Vimalkumar; Santos, Hélder A. (2020)
    Nanoprecipitation is a straightforward method for the production of block copolymer nanoparticles for drug delivery applications. However, the effects of process parameters need to be understood to optimize and control the particle size distribution (PSD). To this end, we investigated the effects of material and process factors on PSD and morphology of nanoparticles prepared from an amphiphilic diblock copolymer, poly(ethylene oxide)-block-polycaprolactone. Using a Design of Experiments approach, we explored the joint effects of molecular weight, block length ratios, water volume fraction, stirring rate, polymer concentration and organic phase addition rate on hydrodynamic size and polydispersity index of the nanostructures and created statistical models explaining up to 94 % of the variance in hydrodynamic diameter. In addition, we performed morphological characterization by cryogenic transmission electron microscopy and showed that increasing the process temperature may favor the formation of vesicles from these polymers. We showed that the effects of process parameters are dependent on the polymer configuration and we found that the most useful parameters to fine-tune the PSD are the initial polymer concentration and the stirring rate. Overall, this study provides evidence on the joint effects of material and process parameters on PSD and morphology, which will be useful for rational design of formulation-specific optimization studies, scale-up and process controls.
  • Toomey, E.; Hardeman, W.; Hankonen, N.; Byrne, M.; McSharry, J.; Matvienko-Sikar, K.; Lorencatto, F. (2020)
    Background: Interventions to change behaviour have substantial potential to impact positively on individual and overall public health. Despite an increasing focus on health behaviour change intervention research, interventions do not always have the desired effect on outcomes, while others have diluted effects once implemented into real-life settings. There is little investment into understanding how or why such interventions work or do not work. Methodological inadequacies of trials of behavioural interventions have been previously suggested as a barrier to the quality and advancement of behavioural research, with intervention fidelity acknowledged as a key area for improvement. However, there is much ambiguity regarding the terminology and conceptualisation of intervention fidelity and a lack of practical guidance regarding how to address it sufficiently, particularly within trials of complex behavioural interventions. Objectives: This article outlines specific issues concerning intervention fidelity within trials of health behaviour change interventions and suggests practical considerations and specific recommendations for researchers, with examples from the literature presented. Conclusions: Recommendations pertain to (1) clarifying how fidelity is defined and conceptualised, (2) considering fidelity beyond intervention delivery, (3) considering strategies to both enhance and assess fidelity, (4) making use of existing frameworks and guidance, (5) considering the quality and comprehensiveness of fidelity assessment strategies, (6) considering the balance between fidelity and adaptation and (7) reporting the use of fidelity enhancement and assessment strategies and their results. Suggestions for future research to improve our understanding of, and ability to, address fidelity in behaviour change interventions are also provided.
  • Hasselmann, Sebastian; Hahn, Lukas; Lorson, Thomas; Schaetzlein, Eva; Sebastien, Isabelle; Beudert, Matthias; Luehmann, Tessa; Neubauer, Julia C.; Sextl, Gerhard; Luxenhofer, Robert; Heinrich, Doris (2021)
    In this study, a novel approach to create arbitrarily shaped 3D hydrogel objects is presented, wherein freeform two-photon polymerization (2PP) is enabled by the combination of a photosensitive hydrogel and an intrinsic support matrix. This way, topologies without physical contact such as a highly porous 3D network of concatenated rings were realized, which are impossible to manufacture with most current 3D printing technologies. Micro-Raman and nanoindentation measurements show the possibility to control water uptake and hence tailor the Young's modulus of the structures via the light dosage, proving the versatility of the concept regarding many scaffold characteristics that makes it well suited for cell specific cell culture as demonstrated by cultivation of human induced pluripotent stem cell derived cardiomyocytes.
  • Hahn, Lukas; Beudert, Matthias; Gutmann, Marcus; Kessler, Larissa; Stahlhut, Philipp; Fischer, Lena; Karakaya, Emine; Lorson, Thomas; Thievessen, Ingo; Detsch, Rainer; Luehmann, Tessa; Luxenhofer, Robert (2021)
    Hydrogels are key components in bioink formulations to ensure printability and stability in biofabrication. In this study, a well-known Diels-Alder two-step post-polymerization modification approach is introduced into thermogelling diblock copolymers, comprising poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine). The diblock copolymers are partially hydrolyzed and subsequently modified by acid/amine coupling with furan and maleimide moieties. While the thermogelling and shear-thinning properties allow excellent printability, trigger-less cell-friendly Diels-Alder click-chemistry yields long-term shape-fidelity. The introduced platform enables easy incorporation of cell-binding moieties (RGD-peptide) for cellular interaction. The hydrogel is functionalized with RGD-peptides using thiol-maleimide chemistry and cell proliferation as well as morphology of fibroblasts seeded on top of the hydrogels confirm the cell adhesion facilitated by the peptides. Finally, bioink formulations are tested for biocompatibility by incorporating fibroblasts homogenously inside the polymer solution pre-printing. After the printing and crosslinking process good cytocompatibility is confirmed. The established bioink system combines a two-step approach by physical precursor gelation followed by an additional chemical stabilization, offering a broad versatility for further biomechanical adaptation or bioresponsive peptide modification.
  • Chen, Wei; Chen, Hao; Zheng, Dandan; Zhang, Hongbo; Deng, Lianfu; Cui, Wenguo; Zhang, Yuhui; Santos, Hélder A.; Shen, Hongxing (2020)
    Gene therapy provides an ideal potential treatment for intervertebral disk degeneration by delivering synthetic microRNAs (miRNAs) to regulate the gene expression levels. However, it is very challenging to deliver miRNAs directly, which leads to inactivation, low transfection efficiency, and short half‐life. Here, Agomir is loaded in hydrogel to construct a gene‐hydrogel microenvironment for regulating the synthesis/catabolism balance of the tissue extracellular matrix (ECM) to treat degenerative diseases. Agomir is a cholesterol‐, methylation‐, and phosphorothioate‐modified miRNA, which can mimic the function of miRNA to regulate the expression of the target gene. Agomir874 that mimics miRNA874 is synthesized to down regulate the expression of matrix metalloproteinases (MMPs) in nucleus pulposus (NP). At the same time, a polyethylene glycol (PEG) hydrogel is synthesized through Ag‐S coordination of 4‐arm PEG‐SH and silver ion solution, which has injectable, self‐healing, antimicrobial, degradable, and superabsorbent properties and matches perfectly with the mechanism of intervertebral disk. By delivering Agomir‐loaded PEG‐hydrogel to a degenerative intervertebral disk, a gene‐hydrogel microenvironment is constructed in situ, which reduces the expression of MMPs, regulates the synthesis/catabolism balance of ECM in the NP of the intervertebral disk, and improves the tissue microenvironment regeneration.
  • Freitag, Tobias L.; Podojil, Joseph R.; Pearson, Ryan M.; Fokta, Frank J.; Sahl, Cecilia; Messing, Marcel; Andersson, Leif C.; Leskinen, Katarzyna; Saavalainen, Päivi; Hoover, Lisa I.; Huang, Kelly; Phippard, Deborah; Maleki, Sanaz; King, Nicholas J. C.; Shea, Lonnie D.; Miller, Stephen D.; Meri, Seppo K.; Getts, Daniel R. (2020)