The menisci consist of fibrocartilage. They are partially (laterally more than medially)
mobile parts of the joint surfaces and compensate for the incongruence of the femur and
tibia. They reduce the joint pressure on the tibial plateau and the femoral condyles and help
to stabilize the joint. Due to this biomechanical relevance, the partial loss of the meniscus
leads to arthritic changes in long term. Suturing the torn meniscus is increasingly becoming
the focus of knee surgery. Degenerative torn menisci have a significantly poorer prognosis
with regard to healing than traumatically torn menisci (e.g. meniscus damage associated with
a cruciate ligament tear).
Indications for partial meniscus replacement are symptomatic, degenerative, and irreparable
damage to the medial and lateral meniscus, possibly with early osteoarthritis of the
compartments, as well as partial loss of the meniscus in the event of anterior knee
instability in young, active patients, in which case simultaneous reconstruction of the
anterior cruciate ligament should be performed. A prerequisite for a good clinical result
after partial meniscus replacement is a stable knee without malalignment in the coronal
plane. Partial meniscus replacement is not suitable in the case of axial deviation and knee
instability, patients older than 60 years, advanced chondromalacia and degenerative changes
in the affected compartment, an extension deficit of more than 3° compared to the opposite
side or a knee flexion of less than 125°. Inflammatory arthritis or synovial inflammation of
the knee and a Body Mass Index (BMI) greater than 30 kg/m² are additional exclusion criteria.
Williams et al. 2007 could show, that 5 years after partial removal of the medial or lateral
meniscus, despite an excellent functional result, 64% of patients showed medial and 33%
lateral cartilage damage on magnetic resonance imaging (MRI). This study highlights the
considerable delay with which the symptoms occur despite already detectable arthritic
changes.
Englund et al. were able to show in a study that patients developed osteoarthritis
significantly more frequently over a period of 30 months if they had meniscus damage than if
they did not. Englund et al. detected tibiofemoral osteoarthritis in 27% of patients 15 years
after partial meniscus removal compared to 10% in a control group that had not undergone
surgery.
In the case of incomplete meniscus loss, where the peripheral rim is sufficiently intact,
defect filling is the only way to restore the lost substance and function of the meniscus. In
the past, an implant made of bovine collagen (Collagen Meniscus Implant (CMI), Stryker) or an
artificial meniscus made of polyurethane (Actifit, 2med) was often used. The CMI has been
withdrawn from the market by the manufacturer, so that no biological treatment alternative
exists.
Schenk et al. were able to show in a recent study for the CMI, consisting of bovine collagen
that, despite a significant improvement in pain and function, the CMI is subject to a
progressive shrinkage process over time. The studies mentioned above make it clear that
partial replacement of the meniscus is necessary if preservation by meniscus suturing is no
longer possible to prevent or postpone arthritic changes.
In the investigator-initiated study on which this application is based, a novel implant made
from demineralized allogenic human cancellous bone (Spongioflex®, DIZG gGmbH Berlin) is to be
implanted into the meniscus defect of the recipient knee. This transplant has sponge-like
properties and therefore facilitates the ingrowth of cells from the surrounding meniscus. The
investigational medicinal product (IMP, Spongioflex®) is de-calcified and demineralized, it
is hard, when dry, but soft when wet. In the knee the conditions are wet, thus it stays soft.
It is pliable (Fig1) and can be easily sutured.
Figure 1: Spongioflex®
The manufacturer (Deutsches Institut für Zell-und Gewebeersatz (DIZG gGmbH)) did a study of
cell ingrowth on Spongioflex®. They describe that ingrowth of cells on Spongioflex® was
observed after 28 days and these cells do not ossify.
Scotti et al. summarizes 2013 the knowledge in respect to meniscal repair as follows:
"In the last decade, striving for optimal restoration of meniscal tissue, the orthopedic
surgeon's armamentarium has been enriched by the use of biocompatible meniscus scaffold and
meniscal allograft transplantation". "However, despite promising short-term results, none of
the current strategies have demonstrated regeneration of a functional, long-lasting meniscal
tissue and re-establishment of a proper knee homeostasis in the meniscectomised knee". "The
rationale for using a cell-free biomaterial to replace part of the meniscus is based on
repopulation of the scaffold by the host cells recruited from the synovium and the meniscal
remnants, and subsequent tissue ingrowth which renders this approach cell-based after
implantation. A mandatory prerequisite is the absence of both knee instability and
malalignment".
This section of the paper of Scotti et al. describes exactly the need for a restoration of
the meniscus. Furthermore it defines exactly the features of a scaffold:
"A biomaterial used as scaffold for meniscus tissue engineering purposes should present many
features. In particular, the ideal meniscal scaffold should be (i) "cell-instructive",
promoting cell differentiation and proliferation if cell-seeded, or cell migration if
cell-free; (ii) "biomimetic", mimicking architecture, tribology and mechanical features of
the native meniscus; (iii) resilient and resistant to withstand mechanical forces acting in
the joint while cells produce extra cellular matrix (ECM); (iv) biocompatible, not evoking
any foreign-body reaction also with its degradation products; (v) slowly biodegradable
allowing to be gradually replaced by biologic tissue; (vi) open, with high porosity, allowing
diffusion of nutrients and catabolic substances; and (vii) easy to handle, to be sutured and
to be implanted by the surgeon".
Pereira et al. describes that a meniscal implant, either for partial or total replacement
should:
"provide the biomechanical properties but also the biological features to replace the loss of
native tissue. Moreover, these approaches include possibilities for patient-specific implants
of correct size and shape".
Spongioflex® fulfils all these demands described by Dabaghi et al., Scotti et al. and Peirera
et al. and it can be adapted in size and shape and thus is in the moment the optimal choice
for partial meniscal replacement.
Dickerson et al. describes that "the scaffold must have a high fluid conductance, concomitant
with high porosity…. Porosity allows more rapid cell incorporation along the surface and
through the thickness of the scaffold, promoting integration with the host tissue.". "The
scaffold must guide cells to regenerate all four zones of the tissue structure".
This is the case of Spongioflex® it is porose and can guide cells. Scotti et al. proposes
2013 to use CMI for partial meniscal regeneration, but this product is retracted from the
market by now and they describe already the shrinking of the transplant. Knee stability and
an aligned knee are a requisite for the study proposed. Dickerson et al. shows that new
fibrocartilage tissue is formed on the demineralized end of the allograft. Results of
Credille et al. support these findings. It will not be ossified again. Smith et al. describes
that "demineralized cancellous bone sponges are Food and Drug Administration-approved and
commercially available products that have the potential to provide biologic and biomechanical
augments for rotator cuff healing. The sponge can act as a scaffold for cellular attachment
and proliferation" .
Credille et al. showed in a recent publication that a biphasic interpositional cancellous
allograft (BioEnthesis; Sparta BioPharma, Inc., Madison, NJ) can be used for rotator cuff
repair. The allograft is "a porous scaffold for endogenous biological factor migration and
thus potentially address the lack of enthesis recapitulation at the rotator cuff repair
interface… while the demineralized layer supports soft-tissue ingrowth while acting as a
"sponge" to hold bone marrow elements at the repair site".
The group around Prof. Moroder from the Charité has used Spongioflex® for glenoid repair.
They describe that the transplant does not calcify again. The glenoid is also no bony
structure. They used the same product in non-bone structures and could show successful
restoration of the glenoid.
Sundar et al. describes that the use demineralized bone matrix increased fibrocartilage when
used for augmentation of rotator cuff repair. The used graft (Spongioflex®) provides a
scaffold for cell migration of meniscal cells from neighbouring parts of the meniscus. The
intended study will show that this kind of allograft is suitable for partial meniscal
replacement because it allows cell migration and has enough porosity to allow fluid
conductance. [24] As described by Wildemann et al. sufficient growth factors are remaining in
the demineralized bone matrix (Spongioflex®) to support new fibrocartilage formation. Scotti
et al. underlines the importance of growth factors for meniscal regeneration.
In summary from the literature, it can be concluded, that Spongioflex® is an attractive
scaffold for partial meniscal repair because it is fully biological, it still has
fibrocartilage inductive factors, allows cell migration, fluid conductivity, resists
biomechanical forces, does not provoke immunoreactivity, it is adaptable in size and can
easily be sutured. Partial meniscus replacement is an established surgical treatment for
patients who have undergone partial meniscus removal, to lead to the ingrowth of cells and
the regeneration of meniscus-like tissue.
The purpose of this investigator-initiated trial is to evaluate whether the novel graft can
prevent/reduce the disadvantages of the previously used replacement materials and shows
better results than the group of patients, which were not operated. Since there is currently
no alternative made of biological material to this product, this investigator-initiated trial
is of great medical and economic importance. The otherwise following arthrosis or knee
prosthesis implantation (TKA) could be prevented or at least postponed. Initial clinical
results are promising.
An important and sensitive parameter for assessing the postoperative function of the meniscus
is the MRI image. Genovese et al. 2007 were able to show in a categorization/classification
which magnetic resonance image can be expected in the case of successful incorporation.
Several studies have shown that the known clinical knee scores (Lysholm, nternational Knee
Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Visual
Analogue Scale (VAS) pain) improve significantly after successful ingrowth of the meniscus
implant.