Bioinspired Wear-Protective Coatings for Osteoarthritis - American

Chapter 9

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Bioinspired Wear-Protective Coatings for Osteoarthritis Larry An,1 Sung Won Ju,1,2 Minsoo Park,2 Jihyung Kim,1 Haewon Choi,1 Song Hoe Koo,1 Jinsoo Ahn,2 and Kollbe Ahn1,* 1Marine

Science Institute, University of California, Santa Barbara, California 93106, United States 2Dental and Biomaterials, School of Dentistry, Seoul National University, Seoul 03080, South Korea *E-mail: [email protected]

Each year more than one million Americans have painful total joint replacement (TJR) surgery with its attendant medical risks. Furthermore, Revision TJR is required due to a number of reasons including microscopic wear-generated particulate debris from wear of the implants, and it is associated significantly greater risks. Whereas collagenous human cartilage tissues do not have a protective coating and have a poor capacity for self-repair of damage, marine mussels protect their soft collagenous core tissues of byssal thread from abrasion using hard and tough cuticles. The mussel cuticle (thickness: 5-10 µm) has shown wear-protective and self-healing properties with unusually high fracture toughness. In this chapter, we discuss an innovative bioinspired toolkit for biocompatible wear-resistant coatings that could protect various biomedical and joint surfaces from wear to diminish the likelihood of revision surgeries.

Introduction Cartilage is the material that cushions the end of bones in a joint (e.g., knees, hips, lower back, neck, and fingers), and allows joints to move smoothly. Wear of cartilage is not inevitable, but cartilage tissues have a poor capacity © 2017 American Chemical Society Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 1 ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


for self-repair of damage that frequently occurs, and that can lead to arthritis and osteoarthritis (OA) (1–3). OA, the “wear-and-tear” arthritis that causes damage to the cartilage surface over time (3), affects about 27 million adults and 300 thousand children in the US alone, resulted in over 50% of the total joint replacements (TJR). Despite urgent need for wear-resistant and self-healing coatings in physiological environments, no breakthrough has been reported because wet conditions have presented an unsurmountable challenge for current synthetic polymeric biomaterials. Biological wear-protecting strategy may provide us a wear protecting tool kit to joint surfaces. Current standard implants for TJR consist of polyethylene, ceramic, and metals. The corrosion resistance of the current femoral components, metal or metal-cermaic alloys (e.g., cobalt-chrominuim or alumina-zirconia), relies on passivation by a thin surface layer of oxide (4). Wear of the femoral and polyethylene components produce nano- and/or microscopic particulate debris in the joint space even with an otherwise completely successful TJR, leading to many risks of periprosthetic inflammation, osteolysis, implant loosening, catastrophic fracture, and other serious health problems (5), resulted in repeated Revision TJR (RTJR). The magnitude of revision surgery and its associated risks are several times greater than those of the index procedure (6). The societal financial burden of RTJR is billons of dollars annually in the US (7).

Mussel Byssal Cuticle: Potential Biomedical Wear-Protective Coatings The wet environment does not appear to restrict biopolymers in marine organisms or marine-inspired catechol-mediated synthetic polymers to coat and adhere to surfaces, and self-repair (8–11). Mussel byssal threads (Figure 1) (12) function primarily as holdfast fibers by securing mussels to solid surfaces in the high-energy intertidal zone where water and suspended sand velocities often exceed 25 m/sec. Thread lifetime would be very short if not covered by a tough protective coating. The Young’s modulus E and hardness H of the mussel byssal cuticle are similar to structural engineering polymers but with 100% elongation-to-break (13), i.e., high “toughness”. Conventional synthetic polymers do not show such a unique combination of material properties; high stiffness usually compromises extensibility. Byssal coating has a specific strain energy density >500 J/g which exceeds Kevlar and dragline silk.

174 Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 1 ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Figure 1. A cross section of mussel byssus comprised of collagenous core and cuticle (thin protective coating for collagenous core). Mussels produce a byssus composed of numerous extensible, shock absorbing byssal threads. The threads are covered by a thin (5-10 µm) cuticle with a granular morphology. Strain-induced macrotearing of cuticle exposing the underlying fibrous core is evident in the SEM (12). Adapted with permission from reference (12). Copyright 2009 ACS.

The capability of its energy-dissipative mechanical properties was described based on strong but reversible coordination complexes between catechol and iron ligands and a cellular structure (10). The structure and chemistry of marine mussel byssal coating (cuticle) could be translatable into a completely synthetic analog capable of protecting joint implant surfaces from wear. The coating consists mostly of dopa (catechol)-containing protein (mfp-1) and has a distinctive filled cellular structure. Resistance to wear is apparently endowed by chemistry in the form of strong but reversible cross-links (e.g, intermolecular multivalent hydrogen bonding of catechols) as well as by a cellular structure that is hard but stretchy. Zuccarello demonstrated (using chymotrypsin digestion) that mfp-1 is not limited to the granules but extends in the form of up to 0.5 μm fibrils from the granule surface into the matrix (14). The granules are hierarchical fuzzy/hairy spheres (200-500 nm diameter) in a matrix that resembles a double polymer network.

175 Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 1 ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


In marine mussels, the process of complex coacervation is suggested to be a critical step in the formation of protein-based underwater coatings and adhesives that efficiently coat surfaces underwater and harden into threads and plaques that are robust enough to uphold strong currents in oceanic tidal zones (15). Wearresistant coatings has been generated by complex coacervate between mfp-1 (a protein constituent of mussel byssal cuticle) and hyaluronic acid (HA) inspired by the mussel cuticle showed excellent damage protection in shear mode with loading (Figure 2) (16). The coacervate solution was injected between two mica surfaces in the Surface Force Apparatus (SFA). The normal and shear forces of the coacervate of mfp-1/HA were measured. The instrument configuration of the SFA (Figure 2B) was considered a key analytical tool in producing meaningful data of the envisaged novel coatings (16). The instrument consists of two cylinders covered with atomically smooth mica sheets that can be precisely programmed to approach contact, and then separate to allow for force measurements from subpico-newton to mN and a distance resonance of less than ~1 Å (17). Fluids such as coacervates was added to the gap and tested in friction by measuring the correlation between parallel F|| and F^ forces (Figure 2B). To measure frictional behavior an additional sliding force F|| was applied at 90° to the normal force F^. The correlation of such data gave the static friction coefficient defined as µ = dF||/F^ (Figure 2C). Wear protection (or resistance) of the coacervate was demonstrated by the magnitude of load before shear-induced damage (Figure 2D). Frictional damage and wear protection to mica were assessed by recording the interference patterns associated with transmission of white light through the mica/coacervate/ mica sandwich at different applied forces (Newton’s rings, Figure 2E). Surface damage such as micro-scratches was detected as defects in the rings. Although the tests of the coacervate of mcfp-1 with HA compared to HA showed a relatively small difference in friction coefficient at ~0.3 and ~0.8, respectively (Figure 2C), the coacervate shielded the mica surface from all frictional damage even to the limiting available normal force of 350 mN. This matches the best performing molecular ball bearings (18), whereas HA alone exhibited severe damage even at a low loading of 25 mN (Figure 2D, E). Beyond wear resistance, mussel adhesive holdfasts exhibit significant self-healing capability in wet conditions (8, 10, 13). This has been replicated in synthetic materials inspired by dopa-metal coordination in the mussel cuticle (11). Furthermore, self-healing of synthetic catechol-functionalized stiff plastics, i.e., polyacrylates and polymethacrylates, in metal-free aqueous media was recently reported (9). In this discovery, intermolecular hydrogen bond formations between catechol functionalities in the damaged area allow the underlying polymer to fuse back together. After about 5-20 minutes, the hydrogen bonded catechols spontaneously disappear leaving the original site of damage completely healed. This reveals a new dimension of catechols, mediating interfacial self-healing through the formation of hydrogen bonds between surfaces that are ultimately augmented or replaced by other types of non-covalent interactions. The underwater cohesive interaction driven by catechol moieties was also observed in a symmetric configuration of dopa-rich mfp-5 (19). The mussel cuticle-inspired coatings will be an innovative toolkit for various biomedical implants requiring wear resistance. 176 Ito et al.; Advances in Bioinspired and Biomedical Materials Volume 1 ACS Symposium Series; American Chemical Society: Washington, DC, 2017.


Figure 2. SFA wear protection measurement of coacervate coating generated from mcfp-1 and HA. A, Bright-field microscopy showing coacervates injected between two glass surfaces. B, Simple schematic of the SFA used in friction testing of coacervates. Not shown is the beam of white light transmitted through the contact zone that produces Newton’s rings by constructive interference. C, Friction coefficient (μ) and D, Wear resistance of mcfp-1/HA coacervates and HA. Data are represented as mean and standard deviation for n=3, p

Bioinspired Wear-Protective Coatings for Osteoarthritis - American

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