by Douglas J. Wyland, MD; and Richard Hawkins, MD
As our population ages, we are not necessarily slowing down. While some
boomers are fine with activities of daily living serving as their
main form of exercise, many are still participating in fairly demanding
sporting endeavors. Todays patients simply desire greater function with
less pain as they pursue their lifes activities. Unfortunately, the pain
and disability caused by
degenerative joint disease (DJD) and traumatic cartilage
defects can veer us all a little off track, but it does not have to be this
Through the past several years, orthopedic investigators have developed
myriad surgical techniques which have been shown to improve our patients
underlying cartilage problems and lifestyles. As we learn from the
plethora of ongoing global research efforts and develop future treatment
strategies, it is becoming clear that we are inching closer to achieving our
goal of altering the natural history of cartilage damage. Future
cartilage regeneration programs will likely consist of a
comprehensive orchestration of patient-matched treatment elements aimed to
enhance the cellular, intra-articular and extra-articular environment in order
to optimize cartilage preservation and restoration.
The concept of preserving and protecting articular cartilage is not new,
although delivering on this worthy goal has been challenging. Several current
nonoperative options provide hope, and breakthroughs are on the horizon which
may actually deliver.
Anthony M. DiGioia,
Injectables such as
viscosupplementation with hyaluronic acid (HA) appear to be a
beacon of light in the midst of many offerings for joint preservation, and may
serve as a core treatment in achieving joint restoration. On a cellular level,
HA injections may work by favorably altering the delicate balance of
pro-inflammatory cytokines (TNF-a, IL-1)
and the chondroprotective agents (TGF-b
IGF-1) in the degenerative joint. Grossly at the intraarticular level, HA
improves the viscoelasticity of synovial fluid by improving shock absorption
and lubrication.Clinically, stand-alone HA injections can provide lasting pain
relief and decreased joint inflammation over simple cortisone injections.
Perhaps more exciting though, HA injections may play a role in cartilage repair
and preservation through decreasing surface fibrillation and even improving
chondrocyte viability after traumatic surface damage.
Other injectables such as
platelet-rich plasma (PRP) and stem cells are being studied
for intra-articular use. PRP has been shown to decrease DJD progression in an
animal model, and clinically has been shown to decrease pain and increase
function. Injected stem cells suspended in HA have shown promise by inducing
healing of partial-thickness traumatized porcine cartilage. Although still in
the lab, we are learning that chondrocyte death which occurs after cartilage
impact can be diminished by the introduction of the antioxidant
This patient had two lesions of the medial
femoral condyle. One area had good enough bone quality for microfracture
(top, left to right) and the other area had more osteonecrosis (bottom, left to
right) thus requiring a single osteoeochondral autograft.
Images: Wyland DJ
Strongly marketed oral supplements such as
glucosamine and chondroitin sulfate are clinically attractive
and show some promise for pain and inflammation relief. Yet along with many
other oral supplements such as dimethyl sulfoxide (DMSO), methylsulfonylmethane
(MSM) and even seaweed extracts, the current scientific evidence is too thin to
recommend these as protective or restorative agents. It is worth noting
however, this was also the thought in the early days of viscosupplementation,
so well stay tuned.
It is important that we consider the chondroprotective effects of
unloading the affected cartilage. This can be achieved by bracing, or
surgically with osteotomy while also addressing the meniscus more
aggressively with repair, replacement with allograft or the promising future
offering of biosynthetic graft with collagen meniscal implant. We should also
consider maximizing the extra-articular environment by properly gaining dynamic
strength, coordination and proprioception of the limb. Of course, these
additions to the program become essential considerations when treating the
patient with surgical techniques designed to preserve and restore cartilage.
We have learned over the last 2 decades that even though the resultant
cartilage produced by our tried-and-true cartilage regeneration procedures is
fibrocartilage, they usually result in good clinical
outcomes. Building on the solid foundation of these techniques, more
sophisticated future advances are aiming to achieve our goal of reproducibly
preserving, repairing and restoring the more desired hyaline cartilage.
Marrow stimulation techniques (MST) such as
microfracture, are the original cell-based therapy and remain
the simplest and most cost-effective surgical treatment for localized
full-thickness cartilage lesions. MSTs introduce undifferentiated mesenchymal
stem cells to the prepared lesion and form a superclot which develops
ultimately into fibrocartilage. Newer reports show that simply introducing HA
to the post-microfractured joint decreases pain and improves the histologic
appearance of the cartilage regenerate. Preparations of BMP-2 and 7 have also
shown promise when introduced in similar animal models.
Autologous chondrocyte implantation (ACI) is a cell therapy
that is swiftly moving from first to third generation techniques. The first
generation procedure currently offered in the United States is a somewhat
cumbersome and expensive strategy requiring two operations, yet unfortunately
results in only equivocal clinical and histological outcomes as compared to the
The future of chondrocyte cell therapy techniques is quite exciting.
Good early clinical and histologic results have been reported using
matrix-induced ACI (MACI), which combines collagen l/lll and
hyaluronan scaffolds with autologous chondrocytes and fibrin glue placed into
the lesion [Hyalograft-C, Fidia SpA]. Another offering in the cell implantation
category includes techniques such as the cartilage autograft implantation
system [CAIS, DePuy Mitek] and DeNovo NT- Natural Tissue Graft [Zimmer], which
deliver to the defect a preparation of minced articular cartilage, combined
with copolymers and fibrin glue. Closer to the horizon of clinical introduction
are other tissue-engineering strategies aimed to convert more accessible
sources of stem cells, such as adipose tissue, into differentiated chondrocytes
that could be placed into a growth-factor laced scaffold and introduced into
the chondral lesion.
This patient had an osteochondritis dessicans
lesion on the medial femoral condyle. It required mosaicplasty with
Osteochondral grafts (OCG) procedures are not exactly
cartilage regeneration, but the adjuvant use of autologous and allogeneic
tissue grafts belong in our joint restoration discussion because OCGs offer a
rather immediate option to restore damaged hyaline cartilage and bone. Future
directions for OCG usage will likely see us combining growth factors and
chondroprotective agents to the already successful procedures in order to
further enhance the incorporation of the graft borders.
Indeed, in the next 20 years we may realize our goal of successfully
creating fairly simple, reproducible arthroscopic procedures which result in
durable native-like hyaline cartilage regenerate.
Joint restoration programs
The future is already here in some centers, as we develop perhaps a new
paradigm for joint restoration by integrating enhancements of the cellular,
intra-articular and extra-articular environments. From the outset, we will
strive to create a sophisticated and comprehensive joint restoration program
for each individual patient. The al la carte program will be
created by the patient and physician and may include elements such as wellness
and therapy, nutrition and supplementation, bracing and injectables, and, if
necessary, the application of appropriate surgical techniques.
We are hopeful that matching patient desires and expectations with the
correct combination of treatment elements will improve outcomes in patients
with both degenerative and focal cartilage disease.
- Ahmed TA, Hincke MT. Strategies for Articular Cartilage Lesion
Repair and Functional Restoration. Tissue Eng Part B Rev. 2010;
Jan 30. Epub ahead of print.
- Jansen EJ, Emans PJ, Douw CM, et al. One intra-articular injection
of hyaluronan prevents cell death and improves cell metabolism in a model of
injured articular cartilage in the rabbit. J Ortho Res.
- Douglas J. Wyland, MD, and Richard J. Hawkins, MD, can be reached
at the Joint Restoration Institute, Steadman Hawkins Clinic of the Carolinas,
200 Patewood Drive, Suite C100, Greenville, SC 29615; 864-454-7422.