Proteoglycan 4 and hyaluronan as boundary lubricants for model contact lens hydrogels

Abstract

Clinical data show that in vitro contact lens friction is related to in vivo comfort. Solutions of biological lubricants hyaluronan (HA) and proteoglycan 4 (PRG4, also known as lubricin) reduce friction at a cornea-polydimethylsiloxane (PDMS) interface. The purpose of this study was to (1) determine if PRG4 can sorb to and lubricate model contact lens materials and (2) assess the boundary lubricating ability of PRG4 and HA compared to saline on model contact lens materials. PRG4 was obtained from bovine cartilage culture and suspended in saline at 300 µg/mL. N,N-Dimethylacrylamidetris (trimethylsiloxy) silane, (DMAA/TRIS) and methacryloxypropyltris (trimethylsiloxy) silane (pHEMA/TRIS) silicone hydrogels were prepared. A previously described in vitro eyelid-hydrogel and cornea-hydrogel biomechanical friction test was used to determine boundary lubricant effect. PRG4 sorption to the hydrogels was assessed using a soak-rinse protocol and western blotting. PRG4 effectively lubricated both silicone hydrogel materials and HA effectively lubricated pHEMA/TRIS, as indicated by a statistically significant reduction in friction compared to the saline control lubricant. An HA and PRG4 combination showed a synergistic effect for pHEMA/TRIS and effectively lubricated DMAA/TRIS. Biological boundary lubricants HA and PRG4 were shown to effectively lubricate silicone hydrogels when in solution. Additionally, HA and PRG4 showed synergistic lubrication for pHEMA/TRIS. The purpose of this study was not to replicate the friction coefficients of contact lenses, but rather to investigate lubricant-surface interactions for common contact lens constituents. These findings contribute to the potential development of biomolecule based lubricant drops for contact lens wearers. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1329-1338, 2018.

Two compartment pharmacokinetic model describes the intra‐articular delivery and retention of rhprg4 following ACL transection in the Yucatan mini pig

“…Uptake of biomaterials and biologics occurs across synovial villi, and is a source of PRG4 synthesis that is under autoregulation . The present study did not involve HA to take advantage of possible synergistic effects with PRG4 . We observed immunopositivity for PRG4 only in the synovium at time 0 (data not shown) but in the absence of a non‐injected surgical control animal we cannot conclude if this represents a lack of porcine PRG4 contribution from the synovium.…”

“…Manufacturing was performed by Peregrine Pharmaceuticals, Inc., Tustin, CA) under pre‐GMP conditions. The presence of O‐linked glycosylations comprised of (β1,3)Gal‐GalNAc was previously confirmed by Western blot and concentration was established by ELISA …”

Intermolecular Interactions between Bottlebrush Polymers Boost the Protection of Surfaces against Frictional Wear

“…These proteins are known to play a key role in the biolubrication and wear resistance of articular cartilage, and using a biomimetic approach, researchers have been able to design artificial lubricants displaying extremely low coefficients of friction (CoF) and high wear protection of fragile soft surfaces. 5,[19][20][21][22][23] The structure of lubricin includes a highly hydrated central domain and two adhesive side domains [24][25][26][27][28][29][30][31] . The central domain consists of a polypeptide backbone bearing heavily glycosylated side chains composed of a significant amount of anionic carbohydrate units such as N-acetylneuraminic acid for lubricin and chondroitin and keratan sulfate moieties for aggrecan 25,32 .…”

Lubrication and Wear Protection of Micro-Structured Hydrogels Using Bioinspired Fluids

“…HA was used as a comparative lubricating fluid for two reasons. First, HA has a key role in the joint lubrication since it binds Agg to form a Agg/HA complexes within the cartilage, osmotically increasing the compressive modulus of cartilage as well with synovial fluid's lubricin and phospholipids to immobilize these molecules onto the shearing contact 5,22,[49][50][51][52][53][54] .…”

“…For example, poly(sodium 4-styrene sulfonate) grafted to poly(hydroxyethyl methacrylate) (p(HEMA)) lowered by almost an order of magnitude the CoF of p(HEMA) hydrogels 20 . The friction can also be decreased upon addition of a lubricating fluid either composed of surfactants 21 , lipids, or naturally-occurring or bioinspired proteoglycans 22 , which are known to be responsible for the lubrication and wear protection of eyes, joints or mucous membranes. Nevertheless, the tools used for the tribological measurement such as tribometers or rheometers, the geometry of the probe (pin or ball on disc), the contact area or the nature and roughness of opposing geometry (glass, metal or hydrogel), highly affects the results and hence should be meticulously described in order to be comparable to other studies.…”