Self-assembling peptides as injectable lubricants for osteoarthritis.
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.
Bell
Carol J
CJ
Institute of Medical and Biological Engineering, School of Mechanical Engineering, University of Leeds, Leeds, West Yorkshire, LS2 9JT, United Kingdom.
Carrick
Lisa M
LM
Katta
Jayanth
J
Jin
Zhongmin
Z
Ingham
Eileen
E
Aggeli
Amalia
A
Boden
Neville
N
Waigh
Thomas A
TA
Fisher
John
J
D000595:Amino Acid Sequence; D001672:Biocompatible Materials; D002356:Cartilage / Q000187:drug effects; D017276:Friction; D006801:Humans; D007267:Injections; D007596:Joints / Q000187:drug effects / Q000502:physiology; D008153:Lubrication; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D010003:Osteoarthritis / Q000188:drug therapy*
D001672:Biocompatible Materials; D009842:Oligopeptides