Copyright © 2008 by The Journal of Bone and Joint Surgery, Inc.
Commentary & Perspective
Commentary & Perspective by
Scott A. Rodeo, MD*,
The Hospital for Special Surgery, New York, NY
Posted July 2008
It has been well-established that a loss of functional meniscus
is associated with an accelerated rate of articular cartilage degeneration.
Thus there is a real need for materials that can replace lost meniscal tissue.
The only currently available option for meniscal replacement is human meniscal
allograft. Although meniscal transplantation is a viable option in selected
knees, there are substantial issues related to cost, graft availability, need
for appropriate sizing, and the technical difficulty of the procedure. In
addition, the procedure may be associated with complicating factors that are common
to all allograft tissues, including delayed and/or incomplete biologic
incorporation, the potential for an immune response that will hinder graft-healing,
and the remote risk of disease transmission. Given these limitations, tissue-engineering
approaches hold tremendous promise for regeneration and/or replacement of
orthopaedic tissues. The collagen meniscus implant is the first such synthetic implant
to be evaluated for meniscal tissue engineering in humans.
The authors of this well-done prospective randomized study
found that patients with chronic meniscal injury (i.e., patients who had
undergone prior meniscal surgery) who received the collagen meniscus implant
regained significantly more of their lost activity than did the patients who
underwent repeat meniscectomy only (42% compared with 29%, p = 0.02). This
finding is presumably attributable to restoration of the load transmission
function of the meniscus. In contrast, the outcomes in patients with acute
meniscal injury who received the collagen meniscus implant were no different
than those in patients who underwent simple meniscectomy. The findings in the
acute injury group are not surprising, since patients are typically able to
return to full and pain-free function following meniscectomy in knees with
minimal concomitant degenerative changes. The improved outcome in patients in
the chronic group suggests that there was abnormal load-bearing function of the
articular surfaces in these patients, although there were no differences in the
baseline Outerbridge scores for these patients as compared with those for the
acute group. The positive effect of meniscal replacement in these patients
supports the concept of replacement of the load-transmission function of the
meniscus. However, despite the improved activity level, there were no
differences in other measures of pain. Perhaps pain scores would have been
improved if the collagen meniscus implant had been used in patients with more
advanced degenerative changes. It must be recognized, however, that the
experience with meniscal allograft transplantation indicates worse results in
patients with more advanced degenerative changes, which is likely due to excessive
mechanical loads on the transplanted tissue.
Despite the improvement in symptoms, this study does not
prove that there is an improvement in meniscal function. Replacement of meniscal function implies restoration of
contact stresses on the articular surfaces to normal as compared with the
increased stresses that occur in the meniscus-deficient compartment. The
biomechanical function of the regenerated tissue following implantation of a collagen
meniscus implant is unknown. This will only be known with long-term assessment
of degenerative changes in these knees. The ultimate goal of a meniscus
replacement device is to alter the natural history of the meniscectomized
compartment. At this time, it is only possible to conclude that meniscal
replacement (using either human meniscal allograft or the collagen meniscus
implant) can improve the patient's current symptoms,
but there is currently no evidence that such implants will improve or restore
meniscal function.
The collagen meniscus implant appears to act as a scaffold
to support ingrowth of meniscus-like tissue. Rodkey et al. reported that biopsies
of the regenerated tissue showed fibrous connective tissue that was
differentiating toward fibrochondrocytic matrix. These biopsy findings
demonstrate that host cells (likely derived from synovium or synovial fluid)
can migrate into the collagen meniscus implant material, differentiate into
fibrochondrocyte-like cells, and synthesize appropriate matrix molecules. The collagen
meniscus implant material is gradually resorbed and replaced by this newly formed
tissue. The biopsy specimens demonstrated areas of mixed fibrous and
fibrochondrocytic tissue, suggesting that the structure and composition of
normal meniscal tissue is not fully recapitulated. The material properties of
this newly formed tissue are unknown. Improvements in such tissue-engineering
approaches to meniscal regeneration will come from further understanding of the
cellular and molecular mechanism(s) of tissue formation in the implanted
scaffold. In particular, we need to know more about the specific cell types
that support new tissue formation, the factors that affect gene expression in
these cells, and the effects of the mechanical environment on function of the
cells in the implant. The use of cytokines, transcription factors, and gene-therapy
techniques may improve the biologic activity of the cells in these scaffolds.
A particular challenge with meniscal replacement is achieving
secure attachment of the implant to the bone and/or remaining host meniscus. The
collagen meniscus implant is designed as a partial replacement, and requires
intact anterior and posterior meniscal horns for suture attachment. In
contrast, complete meniscal replacement with use of meniscal allograft tissue
requires attachment of the anterior and posterior horns of the implant to the
tibial plateau by means of suture through drill holes or attachment by means of
bone plugs or a bone slot to the tibial plateau. Most patients still have some
remaining meniscal tissue at the anterior and posterior horns, so it is likely
that the collagen meniscus implant would be appropriate in many patients after meniscectomy.
One potential concern with an implant that requires attachment to remaining
host meniscus is integration at the host-implant junction. Direct arthroscopic
inspection of the collagen meniscus implant apparently shows secure integration
at this interface.
In summary, the concept of meniscal replacement with use of
synthetic materials that support new tissue formation (i.e., tissue-engineering
approaches) holds great promise as a solution to decrease the risk of
progressive degenerative changes following meniscectomy. Other materials are
also currently under investigation in humans, including a bioresorbable porous
polyurethane scaffold1. Advances in our understanding of
biomaterials, cell function, and extracellular matrix formation will hopefully
suggest new materials and approaches for meniscal replacement and regeneration.
*The author did not receive any outside funding or grants in
support of his research for or preparation of this work. Neither he nor a
member of his immediate family received payments or other benefits or a
commitment or agreement to provide such benefits from a commercial entity. No
commercial entity paid or directed, or agreed to pay or direct, any benefits to
any research fund, foundation, division, center, clinical practice, or other
charitable or nonprofit organization with which the author, or a member of his
immediate family, is affiliated or associated.
Reference
1. Ramrattan NN, Heijkants RG, van Tienen TG, Schouten AJ, Veth RP, Buma P. Assessment of tissue ingrowth rates in polyurethane scaffolds for tissue engineering. Tissue Eng. 2005;11:1212-23.
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