Determination of the<i>in vivo</i>degradation mechanism of PEGDA hydrogels

Browning, Mary Beth; Cereceres, Stacy; Luong, PhamTrungKhanh; Cosgriff‐Hernandez, Elizabeth

doi:10.1002/jbm.a.35096

Cited by 160 publications

(204 citation statements)

References 44 publications

Supporting

Mentioning

201

Contrasting

Order By: Relevance

“…Further, the covalent PEG crosslinking that forms these films is highly stable and to limit any opportunity for encapsulated cells to shed the films in the transplantation environment. 27 …”

Section: Resultsmentioning

confidence: 99%

Characterization of Molecular Transport in Ultrathin Hydrogel Coatings for Cellular Immunoprotection

Lilly

Romero

et al. 2015

Biomacromolecules

View full text Add to dashboard Cite

PEG hydrogels are routinely used in immunoprotection applications to hide foreign cells from a host immune system. Size dependent transport is typically exploited in these systems to prevent access by macromolecular elements of the immune system while allowing the transport of low molecular weight nutrients. This work studies a nanoscale hydrogel coating for improved transport of beneficial low molecular weight materials across thicker hydrogel coatings while completely blocking transport of undesired larger molecular weight materials. Coatings composed of PEG diacrylate of molecular weight 575 Da and 3500 Da were studied by tracking the transport of fluorescently-labeled dextrans across the coatings. The molecular weight of dextran at which the transport is blocked by these coatings are consistent with cutoff values in analogous bulk PEG materials. Additionally, the diffusion constants of 4 kDa dextrans across PEG 575 coatings (9.5×10−10 – 2.0×10−9 cm2/s) was lower than across PEG 3500 coatings (5.9 – 9.8×10−9 cm2/s), and these trends and magnitudes agree with bulk scale models. Overall, these nanoscale thin PEG diacrylate films offer the same size selective transport behavior of bulk PEG diacrylate materials, while the lower thickness translates directly to increased flux of beneficial low molecular weight materials.

show abstract

Section: Resultsmentioning

confidence: 99%

Characterization of Molecular Transport in Ultrathin Hydrogel Coatings for Cellular Immunoprotection

Lilly

Romero

et al. 2015

Biomacromolecules

View full text Add to dashboard Cite

show abstract

“…PEO inhibits protein adsorption by a number of mechanisms including steric repulsion [28,29], blockage of underlying adsorption sites [30], and formation of a repulsive “hydration layer” [31]. Furthermore, PEO has demonstrated in addition to its biocompatibility [32] excellent oxidative stability under biological conditions [33]. Despite the promising performance of PEO coatings in vitro , their performance in vivo has been disappointing and inconsistent [34–36].…”

Section: Introductionmentioning

confidence: 99%

Protein resistance efficacy of PEO-silane amphiphiles: Dependence on PEO-segment length and concentration

et al. 2016

View full text Add to dashboard Cite

In contrast to modification with conventional PEO-silanes (i.e. no siloxane tether), silicones with dramatically enhanced protein resistance have been previously achieved via bulk-modification with poly (ethylene oxide) (PEO)-silane amphiphiles α-(EtO)3Si(CH2)2-oligodimethylsiloxane13-block-PEOn-OCH3 when n = 8 and 16 but not when n = 3. In this work, their efficacy was evaluated in terms of optimal PEO-segment length and minimum concentration required in silicone. For each PEO-silane amphiphile (n = 3, 8, and 16), five concentrations (5, 10, 25, 50, and 100 μmol per 1 g silicone) were evaluated. Efficacy was quantified in terms of the modified silicones’ abilities to undergo rapid, water-driven surface restructuring to form hydrophilic surfaces as well as resistance to fibrinogen adsorption. Only n = 8 and 16 were effective, with a lower minimum concentration in silicone required for n = 8 (10 μmol per 1 g silicone) versus n = 16 (25 μmol per 1 g silicone). Statement of Significance Silicone is commonly used for implantable medical devices, but its hydrophobic surface promotes protein adsorption which leads to thrombosis and infection. Typical methods to incorporate poly(ethylene oxide) (PEO) into silicones have not been effective due to the poor migration of PEO to the surface-biological interface. In this work, PEO-silane amphiphiles – comprised of a siloxane tether (m = 13) and variable PEO segment lengths (n = 3, 8, 16) – were blended into silicone to improve its protein resistance. The efficacy of the amphiphiles was determined to be dependent on PEO length. With the intermediate PEO length (n = 8), water-driven surface restructuring and resulting protein resistance was achieved with a concentration of only 1.7 wt%.

show abstract

“…VacSIM is different from other hydrogels, such as alginates and methacrylates, as well as microneedle and layer-by-layer technology, as all of these require polymerization ex vivo (30)(31)(32)(33)(34)(35). Further, it is different from other self-assembling peptide (SAP) technologies, such as the Q11 peptide, where the antigenic motif must be directly conjugated to the SAP (36)(37)(38).…”

mentioning

confidence: 99%

Vaccine Self-Assembling Immune Matrix Is a New Delivery Platform That Enhances Immune Responses to Recombinant HBsAg in Mice

Grenfell

Shollenberger

Samli

et al. 2015

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

bVaccination remains the most effective public health tool to prevent infectious diseases. Many vaccines are marginally effective and need enhancement for immunocompromised, elderly, and very young populations. To enhance immunogenicity, we exploited the biphasic property of the (RADA)4 synthetic oligopeptide to create VacSIM (vaccine self-assembling immune matrix), a new delivery method. VacSIM solution can easily be mixed with antigens, organisms, and adjuvants for injection. Postinjection, the peptides self-assemble into hydrated nanofiber gel matrices, forming a depot with antigens and adjuvants in the aqueous phase. We believe the depot provides slow release of immunogens, leading to increased activation of antigen-presenting cells that then drive enhanced immunogenicity. Using recombinant hepatitis B virus surface antigen (rHBsAg) as a model immunogen, we compared VacSIM delivery to delivery in alum or complete Freund's adjuvant (CFA). Delivery of the rHBsAg antigen to mice via VacSIM without adjuvant elicited higher specific IgG responses than when rHBsAg was delivered in alum or CFA. Evaluating IgG subtypes showed a mixed Th1/Th2 type response following immunization with VacSIM, which was driven further toward Th1 with addition of CpG as the adjuvant. Increased specific IgG endpoint titers were observed in both C57BL/6 and BALB/c mice, representative of Th1 and Th2 environments, respectively. Restimulation of splenocytes suggests that VacSIM does not cause an immediate proinflammatory response in the host. Overall, these results suggest that VacSIM, as a new delivery method, has the potential to enhance immunogenicity and efficacy of numerous vaccines. Vaccines remain the single greatest public health tool to combat infectious diseases. Vaccine formulation and delivery are key to the ability of vaccines to induce the desired immune responses. One goal of vaccine delivery is to present vaccine antigens in a manner that enhances antigen-presenting-cell (APC) activation, leading to antigen/organism uptake and processing of vaccine antigen(s). Delivery methods or adjuvants that safely enhance vaccine immunogenicity/efficacy are desirable for vaccines that are marginally effective and for vaccines administered to low responders or immunocompromised populations. Additional goals are to reduce the number of doses required to induce effective, vaccine responses and to reduce the amount of vaccine/dose, especially when a single dose of vaccine is administered, as with annual influenza vaccines. Lastly, in pandemics, a vaccine that produces high titers after a single administration would be beneficial. Recent advances in the understanding of how innate mechanisms influence adaptive immunity have led to more rational design in the development of new vaccine adjuvants and delivery systems.Aluminum salts were the first adjuvants licensed for human vaccines in the 1920s. The licensure of non-aluminum salt adjuvants took an additional 80 years (1). One reason for this long gap is that the principles of adjuvant activit...

show abstract

Determination of thein vivodegradation mechanism of PEGDA hydrogels

Cited by 160 publications

References 44 publications

Characterization of Molecular Transport in Ultrathin Hydrogel Coatings for Cellular Immunoprotection

Characterization of Molecular Transport in Ultrathin Hydrogel Coatings for Cellular Immunoprotection

Protein resistance efficacy of PEO-silane amphiphiles: Dependence on PEO-segment length and concentration

Vaccine Self-Assembling Immune Matrix Is a New Delivery Platform That Enhances Immune Responses to Recombinant HBsAg in Mice

Contact Info

Product

Resources

About