A polymer network architecture provides superior cushioning and lubrication of soft tissue compared to a linear architecture.

We report the relationships between linear vs. network polymer architecture and biomechanical outcomes including lubrication and cushioning when the polymers are applied to the surface of articulating knee cartilage. Aqueous formulations of the bioinspired polymer poly(2-methacryloyloxylethyl phosphorylcholine) (pMPC) exhibit tuneable rheological properties, with network pMPC exhibiting increased elasticity and viscosity compared to linear pMPC. Application of a polymer network, compared to a linear one, to articulating tissue surfaces reduces friction, lessens tissue strain, minimizes wear, and protects tissue - thereby improving overall tissue performance. Administration of the network pMPC to the middle carpal joint of skeletally mature horses elicits a safe response similar to saline as monitored over a 70 day period.

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

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.

Friction-lowering capabilities and human subject preferences for a hydrophilic surface coating on latex substrates: implications for increasing condom usage.

Personal lubricants can increase user satisfaction with male condoms by reducing friction and yielding a slippery sensation. However, lubricants pose disadvantages of dilution in physiologic fluids and sloughing away over repeated articulations. To address these drawbacks, a latex surface modification, which becomes lubricious in the presence of physiologic fluid, has been developed and evaluated. This study assesses (i) the frictional performance of the lubricious coating compared to non-coated latex and latex lubricated by personal lubricant, (ii) the level of agreement between human-perceived slipperiness and machine-measured friction, and (iii) human preference for a hypothetical male condom containing the lubricious coating. Friction coefficient of the lubricious coating was 53% lower than that of non-coated latex and approximately equal to that afforded by personal lubricant. A touch test and survey of a small population sample (N = 33) revealed a strong correlation (R 2 = 0.83) between human-perceived slipperiness and machine-measured friction. A majority of participants (73%) expressed a preference for a condom containing the lubricious coating, agreeing that an inherently slippery condom that remained slippery for a long duration would increase their condom usage. Such a coating shows potential to be an effective strategy for decreasing friction-associated pain, increasing user satisfaction and increasing condom usage.

A synthetic polymeric biolubricant imparts chondroprotection in a rat meniscal tear model.

Intra-articular injection of hyaluronic acid (HA) is used to treat osteoarthritis (OA) as a viscosupplement, yet it only provides short-term benefit because HA is cleaved by hyaluronidase and cleared out of the joint after several days. Therefore, we developed a new polymer biolubricant based on poly-oxanorbornane carboxylate to enhance joint lubrication for a prolonged time. Rheological and biotribological studies of the biolubricant reveal viscoelastic properties and coefficient of friction equivalent and superior to that of healthy synovial fluid, respectively. Furthermore, in an ex vivo bovine cartilage plug model, the biolubricant exhibits superior long-term reduction of friction and wear prevention compared to saline and healthy synovial fluid. ISO 10993 biocompatibility tests demonstrate that the biolubricant polymer is non-toxic. In an in vivo rat medial meniscal tear OA model, where the performance of the leading HA viscosupplement (Synvisc-one®) is comparable to the saline control, treatment with the biolubricant affords significant chondroprotection compared to the saline control.

Active agents, biomaterials, and technologies to improve biolubrication and strengthen soft tissues.

Normal functioning of articulating tissues is required for many physiological processes occurring across length scales from the molecular to whole organism. Lubricating biopolymers are present natively on tissue surfaces at various sites of biological articulation, including eyelid, mouth, and synovial joints. The range of operating conditions at these disparate interfaces yields a variety of tribological mechanisms through which compressive and shear forces are dissipated to protect tissues from material wear and fatigue. This review focuses on recent advances in active agents and biomaterials for therapeutic augmentation of friction, lubrication, and wear in disease and injured states. Various small-molecule, biological, and gene delivery therapies are described, as are tribosupplementation with naturally-occurring and synthetic biolubricants and polymer reinforcements. While reintroduction of a diseased tissue's native lubricant received significant attention in the past, recent discoveries and pre-clinical research are capitalizing on concurrent advances in the molecular sciences and bioengineering fields, with an understanding of the underlying tissue structure and physiology, to afford a desired, and potentially patient-specific, tissue mechanical response for restoration of normal function. Small and large molecule drugs targeting recently elucidated pathways as well as synthetic and hybrid natural/synthetic biomaterials for restoring a desired tissue mechanical response are being investigated for treatment of, for example, keratoconjunctivitis sicca, xeroderma, and osteoarthritis.

A Tissue-Penetrating Double Network Restores the Mechanical Properties of Degenerated Articular Cartilage.

Incorporation of an interpenetrating polymer network into an existing single polymer network enables augmentation of the original substrate's mechanical properties, and translation of this concept from purely synthetic materials to natural-synthetic hybrid systems provides the opportunity to reinforce mechanical properties of bulk biological substrates. In many disease states, the mechanical properties of bodily tissues deteriorate rendering them prone to further material failure. Herein, a tissue-supplementing technique is described in which an interpenetrating biomimetic hydrogel is polymerized in situ throughout cartilage tissue. The treatment restores the inferior compressive properties of osteoarthritic cartilage to that of healthy cartilage, preferentially localizing to weaker regions of tissue. Furthermore, the treatment technique preserves cartilage under harsh articulation conditions, showing promise as a materials-based treatment for early-stage osteoarthritis.

Synthesis and structural characterization of high spin M/Cu (M = Mn, Fe) heterobimetallic and Fe/Cu2 trimetallic phosphinoamides.

The heterobimetallic complexes [Mn((i)PrNPPh(2))(3)Cu((i)PrNHPPh(2))] (1) and [Fe((i)PrNPPh(2))(3)Cu((i)PrNHPPh(2))] (2) have been synthesized by the one pot reaction of LiN(i)PrPPh(2), MCl(2) (M = Mn, Fe), and CuI in high yield. Addition of excess CuI into 2 or directly to the reaction mixture led to the formation of a heterotrimetallic [Fe((i)PrNPPh(2))(3)Cu(2)((i)PrNPPh(2))] (3) in good yield. Complexes 1-3 have been characterized by means of elemental analysis, paramagnetic (1)H NMR, UV-vis spectroscopy, cyclic voltammetry, and single crystal X-ray analysis. In all three complexes, Mn or Fe are in the +2 oxidation state and have a high spin electron configuration, as evidenced by solution Evans' method. In addition, the oxidation state of Fe in complex 3 is confirmed by zero-field (57)Fe Mössbauer spectroscopy. X-ray crystallography reveals that the three coordinate Mn/Fe centers in the zwitterionic complexes 1-3 adopt an unusual trigonal planar geometry.