Self‐assembling peptides as injectable lubricants for osteoarthritis

Abstract

The self-assembly of peptides is explored as an alternative route towards the development of new injectable joint lubricants for osteoarthritis (OA). The versatility of the peptide chemistry allows the incorporation of behavior reminiscent of hyaluronic acid (HA), while the triggered in situ self-assembly provides easy delivery of the samples by injection due to the low viscosity of the peptide solutions (that are initially monomeric). Using design criteria based on the chemical properties of HA, a range of de novo peptides were prepared with systematic alterations of charge and hydrophilicity that self-assembled into nematic fluids and gels in physiological solution conditions. The frictional characteristics of the peptides were evaluated using cartilage on cartilage sliding contacts along with their rheological characteristics. Peptide P(11)-9, whose molecular, mesoscopic, and rheological properties most closely resembled HA was found to be the most effective lubricant amongst the peptides. In healthy static and dynamic friction testing (corresponding to healthy joints) P(11)-9 at 20-40 mg/mL performed similar to HA at 10 mg/mL. In friction tests with damaged cartilage (corresponding to early stage OA) P(11)-9 was a less efficient lubricant than HA, but still the best among all the peptides tested. The results indicate that de novo self-assembling peptides could be developed as an alternate therapeutic lubricant for early stage OA.

Hydrogels for the Repair of Articular Cartilage Defects

“…For example, peptide gels with reminiscent chemistry of hyaluronan were designed to increase lubrication between articulating cartilage surfaces. 100 Peptide gels were also designed with binding sites for the growth factor transforming growth factor b-1 (TGFb1), allowing its controlled release based on hydrogel chemistry. 102 Controlled release of TGFb1 using this system caused encapsulated MSCs to differentiate into chondrocytes over 4 weeks in vitro.…”

Bioproduction and characterization of a pH responsive self‐assembling peptide

“…Extensive characterization of the properties of cP 11 -4 has been reported by Carrick et al (2007). Biocompatibility with mammalian cells in tissue culture and the inherent biodegradability of P 11 -4 make it useful as a nanoscale self-assembling material with applications in tissue treatment (Bell et al, 2006;Firth et al, 2006) and bone/dental remineralization (Kirkham et al, 2007). A chemical approach to peptide synthesis is convenient for high throughput analysis of peptide functionality at the design and testing stage, as it is rapid and can be performed at small-scale in parallel.…”

Transient flows in active porous media

“…1). Responsive hydrogels, i.e., hydrophilic polymers embedded and cross-linked into hydrophilic structures [4], can respond to a broad range of stimuli, e.g., pH [5][6][7][8][9][10][11][12][13], temperature [14,15], individual molecules (chemically driven) [16][17][18][19], shear stress [20][21][22][23][24][25], etc., that trigger a change of material properties. In pHinduced responses, hydrogel swelling and deswelling occurs when polymers are ionized by the dynamically changing environmental pH [5].…”

“…Two subgroups that emerge are materials with shear thinning or shear thickening behavior due to the viscoelastic nature of systems comprised of polymers, an intermediate material state at the interface between liquids and solids [20,21]. Applications of shear stress responsive hydrogels include, among others, drug delivery and wound repair [22][23][24][25].…”