Image: University of Alabama at Birmingham

Nanodiamonds designed to toughen artificial joints also
might prevent the inflammation caused when hardworking metal joints shed debris
into the body, according to an early study published in Acta Biomaterialia.

In the race to create longer-lasting and less-painful artificial
joints, University of Alabama at Birmingham
researchers are exploring whether nanodiamond coatings can reduce wear on
joints made of metal alloys. The work is important because, according to the
American Academy of Orthopedic Surgeons, more than 418,000 knee replacements
and 328,000 hip replacements are performed in the United States each year; the
numbers are expected to balloon as the nation’s population ages.

Joint wear generates debris that can cause pain, limit
mobility and hasten joint failure. Debris particles from metal surfaces are
absorbed by scavenging immune cells called macrophages, which then secrete
chemicals that cause swelling and pain. This inflammation turns on bone-eating
cells near implants, and bone-loss increases the likelihood implants will break
loose and require a second surgery.

Diamond coatings may end the shedding of metal debris, but
the constant grinding force within joints can cause even nanodiamonds to shed
some particles. Past studies suggest that diamonds shed less debris and smaller
particles; but, with applications emerging in drug delivery and bio-imaging,
the consequences of particle build-up in organs needs to be known.

Based on the way nanodiamonds interact with macrophages in a
dish, the study authors suggest that the usual size and concentration of wear
debris should cause neither inflammation nor toxicity. The macrophages that
engulf smaller nanodiamonds release fewer inflammatory chemicals than those
encountering larger particles shed by the metal and polymer surfaces of
conventional implants.

“Our results add to the early evidence that nanodiamonds are
indeed nontoxic in living cells,” said Vinoy Thomas, PhD, research associate in
the Department of Physics within the UAB
College of Arts &
Sciences, and corresponding author of the study. “The next step will be to
conduct experiments to confirm where nanodiamond particles of varying sizes and
concentrations end up, and if buildup at those destinations is safe.”

The authors cited a previous study in mice that revealed 60%
of injected nanodiamond particles are deposited in the liver within a half hour
of dosing; the remainder was deposited in the spleen and lungs. Those exploring
nanodiamonds as delivery vehicles for drugs would be counting on these
tendencies.

Fewer the better

In the current study, macrophages were exposed to synthetic nanodiamonds of
varying sizes (6, 60, 100, 250, and 500 nm) and concentrations (0, 10, 50, 100,
200 ug/mL).

At concentrations of less than 50 ug/mL of solution (at
which they typically occur as debris), nanodiamonds were not toxic to
macrophages, which continued to thrive and metabolize energy regardless of
particle size, according to the study authors. Once the concentration of
nanodiamonds exceeded 200 ug/mL, macrophage viability dropped by up to 50%
regardless of particle size.

In addition, nanodiamond exposure significantly reduced
expression of several genes known to play roles in inflammation and related
bone loss when compared to metal and plastic particles, including tumor
necrosis factor (TNF)-?, interleukin (IL)-1?, chemokine Ccl2, and platelet
derived growth factor (PDGF). Researchers contend that smaller size and lower
concentration meant nanodiamonds were engulfed by macrophages that released
fewer inflammatory chemicals that turned on fewer harmful genes.

“Past studies on diamond-joint surfaces have shown a marked
reduction in wear-debris volume compared to first-generation alloy and
polyethlene joint parts, but the work continues to ensure they are safe,” said
Yogesh Vohra, PhD, director of the UAB
Center for Nanoscale
Materials and Biointegration and senior author on the study. “We hope the
reduced wear volume and particle size expected for diamond articulation will
represent a major advance over conventional orthopedic bearings.”

“This study provides the insight necessary for us to
continue our nano-toxicological evaluation of nanodiamond particles,” said
Namasivayam Ambalavanan, MD, professor in the Department of Pediatrics within
the UAB School of Medicine, and study co-author.

SOURCE – University of Alabama at Birmingham