A Synthetic Bottle-Brush Polyelectrolyte Reduces Friction and Wear of Intact and Previously Worn Cartilage

Abstract

A poly(7-oxanorbornene-2-carboxylate) polymer containing pendent triethyleneglycol (TEG) chains of 2.8 MDa (“2.8M TEG”) was synthesized and evaluated for long-term lubrication and wear reduction of ex vivo bovine cartilage as well as for synovitis in rats and dogs after intra-articular administration. Bovine cartilage surfaces were tested under torsional friction for 10,080 rotations while immersed in either saline, bovine synovial fluid (BSF), or 2.8M TEG. For each solution, coefficient of friction (μ), changes in surface roughness, and lost cartilage glycosaminoglycan were compared. To directly compare 2.8M TEG and BSF, additional samples were tested sequentially in BSF, BSF, 2.8M TEG, and then BSF. Finally, another set of samples were tested twice in saline to induce surface roughness and then tested in BSF, Synvisc, or 2.8M TEG to determine each treatment’s effect on worn cartilage. Next, male Lewis rats were injected in one knee with 2.8M TEG or saline and evaluated for effects on gait, and female beagles were injected with either 2.8M TEG or saline in one knee, and their synovial tissues analyzed for inflammation by H&E staining. Treatment with 2.8M TEG lowers μ, lessens surface roughness, and minimizes glycosaminoglycan loss compared to saline. The 2.8M TEG also reduces μ compared to BSF in pairwise testing and on worn cartilage surfaces. Injection of 2.8M TEG in rat or beagle knees gives comparable effects to treatment with saline, and does not cause significant synovitis.

Mega macromolecules as single molecule lubricants for hard and soft surfaces

“…With regards to the relative COF performance of the 9 MDa mega HPG-3 to other lubricants, it is challenging to compare as the extracted absolute values depends on the measurement geometry and protocol, as well as tissue type. Given the above caveats, the COF values of the mega HPGs are roughly an order of magnitude lower than the values reported for some bottle-brush copolymer lubricants between cartilage and glass surfaces 47,50 , while on par with linear polyelectrolyte polymers between cartilage and cartilage surfaces 51 (comparative study results presented in Supplementary Information COF chart; Supplementary Table 5). Analysis of the flow data reveals only the solution of mega HPG-1 (1 MDa) at 23% shear thins mimicking that of Synvisc, although with a smaller change in viscosity as a function of shear rate ( Supplementary Fig.…”

Recent progress of bioinspired cartilage hydrogel lubrication materials

“…Inspired by this unique structure, Klein et al used polystyrene to fabricate polystyrene brushes on the surface of mica; a low coefficient of friction (COF) (<0.001) could be obtained between sliding surface under the contact pressure around 10 atm [45]. Since then, several kinds of polymer brushes have been carried out to fabricate brushstructure on different substrates, and their lubrication mechanisms in aqueous media are summarised as hydration lubrication [46][47][48][49][50][51].…”

Proteoglycans in Biomedicine: Resurgence of an Underexploited Class of ECM Molecules

“…Synthesized via ring-opening metathesis polymerization, the polymer biolubricant showed promise in reducing friction and offering chondroprotection in ex vivo plug-on-plug and rat models of osteoarthritis (Wathier et al, 2013;Wathier et al, 2018). Further efforts to improve the polymer to make it better match the osmolarity of synovial fluid are being conducted by making it less anionic and covalently conjugating pendent triethylene glycol (TEG) chains to it (Lakin et al, 2019). A note about lubricin-it is debated whether this molecule is a glycoprotein or a proteoglycan, since it is a glycosylated protein that does not have traditional glycans such as CS, DS, or heparin attached to a protein core, and the protein itself is glycosylated.…”

“…Duchenne muscular dystrophy (Amenta et al, 2011;Ito et al, 2017;Fallon and McNally, 2018) Fibromodulin Keratan sulfate Diabetic wounds and neuropathy (Jian et al, 2013;Zheng et al, 2014;Jazi et al, 2016) Neointimal hyperplasia (Ranjzad et al, 2009) Bone regeneration (Zheng et al, 2012;Li et al, 2016) Tendon healing (Delalande et al, 2015) Breast cancer metastasis (Dawoody Nejad et al, 2017) Lubricin None Osteoarthritis (Iqbal et al, 2016;Lakin et al, 2019;Larson et al, 2016;Ludwig et al, 2012;Wathier et al, 2013;Lawrence et al, 2015) Ocular applications, dry eye (Lambiase et al, 2017;Oh et al, 2017b;…”