Abstract
Osteoarthritis (OA), a disease associated with cartilage damages inside the joints, affects millions of people
every year. The current medicines, including analgesics and anti-inflammation drugs only alleviate symptoms
but do not cure the disease while surgical methods to use replacement cartilage auto- or allo-grafts struggle with
the problems of infection, donor-site morbidity, immune-rejection and limited tissue supply. In this regard,
regenerative engineering approaches which are based on biomaterial scaffolds, stem cells and biological growth
factors to construct artificial replacement cartilage tissues have become an important field. While growth factors
are powerful, these chemicals pose a significant concern regarding to their toxic and side effects. Alternatively,
electrical stimulation (ES) has been known to exhibit a significant effect on promoting bone and cartilage growth.
As bioelectricity is an intrinsic physiological signal of living organisms, the use of ES presumably, offers a more
natural approach for inducing cartilage growth. However, while extracorporeal electrical stimulators are not
effective, implanted devices rely on toxic batteries, requiring invasive surgery for removal, which can easily
damage the healing tissues. In this regard, we have developed a novel biodegradable piezoelectric nanofiber
scaffold, made of PLLA (Poly-L-lactide) and shown that this scaffold can self-generate ES under applied joint
force to heal cartilage defects in small animal models. Yet remaining important questions still need to be
addressed. These questions are (1) what the optimal stimulation and the best piezoelectric biodegradable
scaffold are for cartilage healing and (2) whether the scaffold with physical exercise can heal the major cartilage
defects in large animals. Here, we propose, for the first time, a new biodegradable piezoelectric
nanocomposite cartilage-graft (containing PLLA and magnesium oxide – MgO nanoparticles), and study
an optimal physical-exercise to obtain a novel regenerative approach which can heal critical-sized
cartilage defects in large animals. Accordingly, the work is designed with three specific aims; Aim 1 is to
characterize the proposed biodegradable piezoelectric composite scaffold in vitro to obtain a good replacement
cartilage graft. Aim 2 is to study and assess optimal physical exercise (duration, frequency, and intensity) and
optimal composite scaffolds for the best healing of cartilage defects in rabbits. Aim 3 is to study and demonstrate
cartilage healing in large animal model (sheep). The first milestone (in 1.5 years) is to find out the best
piezoelectric scaffold with desired properties in vitro. The second milestone after 3.5 years is to find out the
optimal physical training and scaffold to heal cartilage defects in rabbits. The final milestone (after 5 years) is to
demonstrate the ability of the MgO/PLLA scaffold with derived optimal joint load (N/m2) and treadmill training to
heal critical-sized cartilage defects in sheep.