TISSUE ENGINEERED APPROACHES TO THE TREATMENT OF
AHLBACK STAGE I-II KNEE OSTEOARTHRITIS: CLINICAL EXPERIENCE
WITH HYALOGRAFT-C AND UNLOADING OSTEOTOMY
STEFANO ZANASI
POLICLINICO DI MONZA
UNITA’ OPERATIVA DI ORTOPEDIA E TRAUMATOLOGIA
RESPONSABILE: DR. STEFANO ZANASI
e-mail: zanasis.orth@virgilio.it
INTRODUCTION
Gonarthritis is due to altered distribution of stresses at the knee: the beared stresses go
beyond the biological joint resistence.
Varus alignment is the most common alignment in OA: up to 75% of all patients have it. In
term of cartilage degradation of the tibio-femoral compartments, the medial side is usually
the worst affected although patello-femoral arthritis is frequently accompanied. Subjects
with varus knee alignment are bowlegged and have negative hip-knee-ankle angles: the
condition is common and does not impose functional restraints unless the varus is severe.
Progressively this condition causes knee instability and subluxation, expecially if the ACL
is lax. Subluxation is common in oblique knee condition in which the joint surfaces have an
exaggerated lateral to medial downward tilt: an arthritic disease pattern of joint
involvement is related to alignment through cause or effect both. The frequent patellar
malalignment in OA probably indicates that the long bones have torsional abnormality at
the level of the patello-femoral mechanism: lateral displacement of patella in the varus
condition have seen in about 30% of patients (Harrison MM et AA Clin Orthop 1994-309:
53-56).
Valgus alignment deformity is less common than varus pattern: it often arise from disease
like renal rickets, polyostotic fibrous dysplasia, developmental displasias and rheumatoid
arthritis and is seen more often in women than in men. Correctional osteotomies for valgus
abnormalities should be made whenever is possible at the centers of rotational alignment.
Subjects with valgus alignment are knock-kneed and have positive HKA angles. The Q
angle is greater than normal and vector forces acting on the patella predispose it to sublux
laterally. Initial enthusiasm for using a proximal tibial varus osteotomy to correct a valgus
deformity of the knee waned after data showed that the results of this operation were often
unsatisfactory (Shoij h. et AA J B J S Am 55:963-973,1973). This procedure will allow
the postponement of joint replacement surgery in the high-demand patient while not
adversely affecting the technical demands or clinical results of a later TKA.
Proximal tibial valgus osteotomy (HTO) has proven to be an effective operation for medial
compartment OA in the young patient who is of too high demand by reason of age, size,
occupation, or lifestyle for unicompartmental or TKA.
After unloading high tibial osteotomy the ratio of bone mineral density of the medial
femoral condyle to the lateral femoral condyle decreases sharply within one year
according to Pauwels law (bone quantity is directly linked to the size of applicated forces)
(Akamatsu Y et AA Clin Orthop 1997 Jan 334:207-214). Aim of the unloading osteotomy is
to redistribute the loading forces bringing them under the limits of joint tolerability: best
results have been obtained when anatomical axis is from 5 to 15° valgus (Yasuda K et AA
Clin Orthop 1992 282:186-195), but correction amount should be not too important or must
be at the 62% of the tibial external plate.
Although the incidence of proximal valgus osteotomy for OA has decreased because of
advances in total knee arthroplasty, there is still a need for this operation in the young
high-demand patient with medial compartment OA.
1
A success rate of 82% HTO alone was reported in patients under the age of 60 who
wished to participate in vigourous sport or work activities (running, jumping. etc) (Nagel A t
AeA, JBJS Am 78:1353-1358, 1996). Other reports in the literature have yielded success
rates from 60% to 70% at 10 years for HTO alone.
HTO with additional Pridie drilling or abrasioartroplasty associated with continuous passive
motion showed cartilage regeneration thicker and more stable, sometimes covering all of
the preexisting erosions in confront of groups without additional operative arthroscopy
(Schultz et AA Knee surg Sport Traumat Arthrosc 1997 7(1):29-36). In addition HTO with
artroscopic abrasion arthroplasty promotes fibro-cartilage regeneration in osteoarthritic
knee with eburnation (Akizuki S. et AA Arthroscopy 1997 Feb 13(1), 9-17). But overall
Maynou c (et AA Acta Orthop Belg 1998 Jun 64(2):193-200) stresses that concomitant
correction by HTO allows to relieve stresses from the chondral grafts and Tom Minas
underlines that “complex and salvage treatment cases having adjuvant treatment including
valgus tibial (n=24) or tibial tubercle (N=15) osteotomies at the 2 ys f.up show statistically
significant functional improvements with patients satisfaction at 24 ms. for simple, complex
and salvage categories of 60%, 70% and 90% respectively (Clin Orthop 2001 Oct (391
suppl) S349-361)
Cartilage has limited self-repair capabilities and articular cartilage defects will ultimately
result in chronic tissue losses. To contrast this relentless outcome new reconstructive
techniques have been developed such as autologous cultured chondrocyte implantation
whose medium-term results are encouraging but with limitations like problematic handling
of cultures in suspension, complicated surgical procedure, chondrocyte de-differentation
(cells acquire a fibroblastoid phenotype and loose the capacity to produce the typical ECM
molecules able to regenerate a physiological-like tissue). Hyaluran-based tissue
engineering by the use of biomaterials derived from jaluronic acid (Hyaff-11) realizes an
ideal three-dimensional scaffold for the cultivation of human autologous chondrocytes that
is able to restore the differentiated phenotype maintaining chondrocyte capability to
produce collagen type II (hyaline cartilage marker) by associating an improved and
simplified implant technique. The bio-engineered tissue due to its 3D structural an physical
properties very closed to the lost cartilage realizes an optimal filling of the tissue gap,
stable on large defects, with resurfacing of complete articular surfaces: in these cases
unloading/corrective osteotomy is usually concurrently associated. Tibio-femoral, patellofemoral malalignment, as well ACL insufficiency or bone insufficiency (ostheocondritis
dissecans, avascular necrosis, ostheochondral fractures) must be managed prior to, or
concurrently managed with the chondral injury.
According to Tom Minas treatment classification (Am. J. Knee Surg. 2000; 13(1):41) ICA
represent the gold standard for SIMPLE cases in healthy knee with unipolar isolated
lesion to the weight bearing femoral condyles and no other surface exhibiting greater than
Outerbridge grade I or II chondromalacia. In COMPLEX cases
for single
extensive/massive unipolar chondral defect or multifocal lesions of the femoral condyles,
tibial plateau, trochlea or patella, concurrently with concomitant realignment procedures or
ACL reconstruction or prior to staged bone graft, ACI represents as well as in coin lesions,
the fist line of treatment able to restore a durable neo-reonstructed hyaline-like cartilage
with satisfactory results in over 85% of cases of condyle and troclea defects and in 65% of
tibial and patellar defects. With different clinical expectations and prognosis SALVAGE
procedures are performed for posttraumatic or degenerative osteoarthritis Ahlback stage
0 or stage I (joint space narrowing lesser than 50%) or kissing lesions in generalized
chondromalacia greater than Outerbridge grade II: ICA is performed concurrently with
realignment procedure and ACL reconstruction and prior to bone grafting. In these patients
younger than 55-58 years-old who want to avoid, or better to delay, TKA and strongly
require, as alternative, resurfacing, we have obtained extremely promising results.
2
PREOPERATIVE PLANNING AND 1ST ARTROSCOPICAL PROCEDURE
The Hyalograft-C ACI protocol requires clinical examination (anamnesis), X-Rays in
orthostatism and assial X-Rays of patella, NMR and arthroscopy.
Cartilage biopsy of 150 mg is arthroscopically taken from a nonbearing area (notch-plasty).
Chondrocytes are cultured in vitro and on 14th day seeded on Hyaff scaffold for cartilage
formation into two weeks
SURGICAL TECHNIQUE
A. High valgus osteotomy according to Puddu: the plates present two serie of holes, one
proximal for two cancellous AO screws and one distal for two cortical AO screws; a
different thickness tooth from 5 to 15 mm (5-7,5-10-12,5-15mm): aim of the plate is the
osteotomy syntesis; aim of the tooth is to avoid the bone collapse with related lack of the
established correction
Le placche hanno due fori ,uno prossimale ed uno distale, per una vite AO da spongiosa
(prossimale) ed una vite AO da corticale (distale); ed hanno un dente di vario spessore da
5mm a 15 mm;la profondità del dente è uguale per tutti ed è di 4mm. Scopo della placca è
la sintesi dell'osteotomia mentre il dente deve prevenire il possibile collasso dell'osso con
la conseguente perdita della correzione voluta. L'unico strumento accessorio è una
forchetta graduata a cuneo che ,introdotta nell'osteotomia,e spinta a colpi di mazzuolo
deve aprire il cuneo per i mm decisi preoperatoriamente sull'esame radiografico.Il focolaio
osteotomico viene mantenuto aperto e la placca viene introdotta nello strumento a
forchetta. Una volta che la placca è inserita si controlla in amplificatore la correzione
ottenuta e si passa alla sintesi ed all'applicazione del trapianto osseo di cresta iliaca se
l'osteotomia è da 7,5 a 15mm,mentre se l'osteotomia è di 5 o 7,5mm è sufficiente utilizzare
dell'osso prelevato dalla tibia distalmente alla osteotomia stessa. Incidiamo cute e sotto
cute fino ad arrivare ai tendini della zampa d'oca con una incisione longitudinale mediana
da 12-14 cm.Quindi sezioniamo a tutto spessore,trasversalmente,il fascio superficiale del
legamento collaterale interno,che sarà lasciato aperto anche a fine intervento.I tendini
della zampa d'oca vengono dissecati e caricati distalmente,quindi con uno scollaperiostio
si libera la tibia e a questo punto i vasi vengono protetti da un divaricatore introdotto
postero medialmente.Sotto controllo fluoroscopico si introduce un chiodo di Steinmann
che parte a circa 4cm dal piatto tibiale interno e si dirige obliquamente e prossimalmente
fino ad arrivare ad 1cm circa al di sotto del margine esterno del piatto tibiale esterno. Non
è mai necessaria una osteotomia di perone. Quando il chiodo è nella posizione
desiderata,con la sega e con l'osteotomo si esegue l'osteotomia tibiale fino ad arrivare a
circa 5mm dal margine esterno della metafisi tibiale.Tale tessuto osseo servirà da cerniera
ed in associazione alla placca garantirà la stabilità dell'osteotomia.Quindi valgizzando il
ginocchio si esegue la clasia della corticale esterna e l'apertura del focolaio osteotomico
ove viene introdotto lo strumento divaricatore a forchetta graduato.Battendo su questo
strumento l'osteotomia viene aperta fino alla misura decisa e a questo punto si introduce la
placca con il dente adatto. Sotto amplificatore di brillanza e con un filo metallico si cercano
i reperi:testa del femore- centro della cavilgia e si controlla dove passa il filo metallico
nell'articolazione del ginocchio.Il filo metallico dovrebbe essere esterno al profilo rotuleo in
antero-posteriore o passare esattamente nel punto del piatto tibiale esterno scelto
dall'operatore sulle radiografie sotto carico. Quindi si passa alla sintesi con due viti AO
,una da spongiosa prossimale e da corticale distale.Una volta certi della qualità della
sintesi il focolaio viene riempito con attenzione di osso autologo tibiale o con LUBBOCK a
3
seconda del dente utilizzato.Il collaterale interno viene lasciato aperto in quanto essendo il
fascio superficiale e non il profondo non arreca alcun danno alla stabilità del ginocchio
B. Surgical procedure by mid line standard arthrotomy is performed at 60 days. After
lesion curettage (abrasion) by a simple curette or a low power burring of the back of the
lesion we proceed to realize a net cut of the edge of the lesion up to the normal cartilage
tissue. Then, if the bed is sclerotic we perform drilling in order to decrease the high local
pressure to relieve pain and to allow a good uptake. Naturally it could be said that stem
cells from the bone marrow could colonize with fibroblasts, but in the saples we have taken
after the 2nd look arthroscopy we never verified a mixed population of the cartilage like
fibro-cartilagineous tissue.
The Hyalograft-C patches are gently pushed in the lesion and trimmed if needed to match
the shape of the defect: when the lesion is contained but wide I resort to resorbable 4-0
stay sutures. If the lesion is uncontained I resort to resorbable microanchors to fix the graft
in order to avoid the sliding and removal during motion.
Postsurgical treatment consists of articular drainage in an area far from the graft, and
compressive bandage for 24 hours postgrafting. Articular movement is forbidden for 24
hours starting with passive rehabilitation with CPM from the 2nd day postop. concurrently
with isometric exercises for quadriceps muscles. Articular weight-bearing may be applied
from the 5th week postop and gradually brought to normal activity at 12-20 weeks. Control
visit are performed at 1,3,6,12,18 months from surgery. NMR is performed at 3 and 6ms
postop; arthroscopic second look with biopsy for hystological tissue typization is performed
at 12 monts postop.
PATIENTS AND METHODS
94 of 187 patients treated from May 1999 to June 2002 for chondral defects Outerbridge
III/IV have been followed: 46 out of 94 were complex or salvage procedure according to
Tom Minas classification.
Complex procedures (30 cases) include: massive unipolar shouldered defects of the
lateral condyle (13 cases), and massive unipolar medial condyle defects plus lateral
condyle or troclea coin lesion (15 cases) that have concurrently respectively managed by
low varus femoral osteotomy and by high valgus osteotomy; plurifocal coin defects ( 2
cases).
Salvage procedures (16 cases) include: 3 cases of limited and shouldered coin kissing
lesions not requiring realignment procedures (<50% emi-joint rime), 12 cases of
unicompartmental O-A and unshouldered kissing lesions and 1 case of aseptic
osteonecrosis of medial femoral condyle that have been concurrently managed with filling
by Norian and unloading corrective osteotomy. In particular 61% 28/46) of these cases,
that is 30 % of the whole cases serie (28/94) have been concurrently managed by
unloading osteotomy according to Puddu technique. The overall population was between
27 and 56 years old (average 42 years old), 57% female, with an average size of the
defect of 12 cm2 (range 7.5 – 32 cm2)
28/94 patients who had been treated with HTO and Hyalograft C for cartilage lesions of
the knee have been reviewed retrospectively; the results of the functional outcome were
prospectively obtained. Being this investigation observational and voluntary in nature, no
inclusion or exclusion criteria have been applied. However, participating surgeons were
encouraged to primarily include patients with a follow-up time from Hyalograft C
implantation of at least 12 months. Data collection was based on a Case Report Form
which has been designed taking into account the most recent guidelines of the
International Cartilage Repair Society (ICRS) discussed at the 3rd ICRS meeting of April
4
28, 2000 in Gotheborg (21). The average follow-up time for this series of patients was 19
months (range 12-47). They were 12 males and 16 females, with a mean age of 41.4
years (range 34-55) affected by chondral defects of the knee caused by trauma (34.6 %),
osteochondritis dissecans (11.8 %) and lesions that were degenerative and/or
microtraumatic in nature (53.6 %). 76.6.% of the subjects had a single lesion, and the
remaining 23.4% multiple lesions, corresponding to a total number of defects of 138,
averaging 1.2 defects per patient. As expected, the vast majority of the defects were
localized on condyle (74.6%): primarily on the medial femoral condyle (63.8%), the
remaining on the lateral condyle. The remainder of the defects was localized on the
throclea (8.7%), patella (8.7%), and tibial plateau (8.0%). The defects treated were graded
Outerbridge IV in the vast majority of cases (85.4%) and grade III in the remaining
percentage. The mean surface area implanted per patient was 3.42 cm 2 (SD=2.57)
ranging from 0.75 to 12.25 cm2. More than half of the patients (53.2 %) had undergone
previous surgery on the affected knee. Remarkably, 36% of the total population had been
previously subjected to cartilage surgery, including debridement and bone marrow
stimulation techniques, which eventually proved unsuccessful. 29.7% of patients had
underwent previous meniscus and/or ligament surgery. 28% of patients underwent one or
more associated surgical procedures at the time of Hyalograft® C grafting. These included
high tibial valgus osteotomy and/or patellar realignment osteotomy (in 7.2% of the
population) and meniscus and/or ligament surgery (24.3%).
Hyalograft® C was implanted without any coverage or fixation system in 58.6% of the
cases, whilst fibrin glue and/or sutures were used in 34.2 % of the cases. The functional
outcome was obtained using 4 endpoints: patient’s subjective evaluation of knee
conditions and quality of life, surgeon’s knee functional test, arthroscopic evaluation of
cartilage repair and histological assessment of the grafted site.
Patients were asked for a subjective evaluation of the knee symptoms and physical
function using the IKDC Subjective Knee Evaluation Form (21), and for their quality of life
using the EuroQol EQ-5D questionnaire (22). Baseline data were obtained by asking
patients to answer these questionnaires retrospectively for the conditions of their knee and
their quality of life after injury but just before Hyalograft® C implantation. Knee functional
outcome was obtained by the surgeon according to the IKDC objective knee examination
form (21). Thirty-seven patients underwent second-look arthroscopy, performed as a
consequence of an adverse event in four cases and for investigative purposes subsequent
to patient’s consent in the remaining cases. Quality of the repair tissue was classified
according to the integration of the graft into the surrounding cartilage (0–4 points), the
degree of defect fill (0–4 points), and the macroscopic appearance (0–4 points), giving the
best possible defect-repair score of 12 points (6). Twenty-four patients out of the 37 who
underwent second-look arthroscopy consented for a biopsy harvesting in the area of graft
implantation. Samples were analyzed by two independent, blinded investigators, who rated
regenerated cartilage as hyaline-like, fibrocartilage or mixed tissue based on criteria of
cellularity, cell distribution, matrix composition and collagen type I and II
immunolocalization. Finally, the occurrence of adverse events in the post-op period was
recorded. The entire set of data was included in a unique database. Statistical analysis
was performed using the SAS system statistical software package (SAS Institute, Cary,
North Carolina, USA). An one year MRI scan, video arthroscopy and biopsy of the repair
have been made
Results
Patient’s assessment of knee conditions and quality of life (N=28). 92.7% of the patients
experienced a subjective improvement in knee function and symptoms. Only 7 patients
(6.4 %) resulted having a worsening of their knee conditions at the follow-up control with
5
respect to pre-surgery status. The mean subjective IKDC score obtained was 36.8 (SD =
12.1) at baseline and 73.1 (SD = 21.3) at the follow-up control. The difference proved
statistically significant (P<0.0001, Student’s t-test, Fig. 1A). 89.9% of patients experienced
an improvement in their quality of life, as assessed by the EQ-VAS. The situation was
found to be unchanged in 6 patients and worsened in 5 patients (4 of them experienced a
worsening also in the subjective knee evaluation scores). The difference in the mean EQVAS score (Fig. 1B), which changed from 61.0 (SD = 16.7) to 84.3 (SD = 17.1) was
statistically significant (P< 0.0001, Student’s t-test). As expected, the majority of the
improvements was related to mobility (63 % of patients improved), usual activities (68 %)
and reduced pain/discomfort (83 %). When the IKDC subjective outcome was analysed in
function of lesion size and time from Hyalograft C implantation, a positive trend of
subjective improvement has been observed with increasing size and follow-up times (Fig.
2 A and B). Clinical symptoms (pain, lock, swelling, full/partial giving way) significantly
decreased within the 3rd month, and completely ceased, in all cases, within 6 months with
good functional recovery and significative improvement of ROM (flex-ext >15%) with
average pre-op. active ROM of 110° (range 80° - 140°) and average post-op active
ROM of 130° (range 110° - 140°). We verified satisfactory clinical results at 18 ms
average f.up : best functional results in high valgus osteotomy (26/46) vs. low varus
osteotomy (2/46). As reported in other serie.(Maynou C. et AA Acta Orthop Belg 1998
Jun; 64(2): 193-200) concomitant correction by high tibial osteotomy allows to relieve
stresses from the chondral grafts. Complex and salvage treatment cases having adjuvant
treatment as valgus tibial or varus femoral osteotomies at the 18 ms. f.up. showed
statistically functional improvements. Patients satisfaction at 24 ms. for complex and
salvage procedures –as Minas cases serie - is about 75% and 90% respectively. The
results for all patients with greater 12 ms. follow up are aggregate scores for the overall
group. Although these results demonstrate marked clinical and statistical significance, the
outcome are clearly superior for the healthy knees ( complex cases) when separated from
the knees with evidence of ostheoarthritis (salvage). Although the salvage cases also
significantly are improved, the sample size is too small. Surgeon’s knee examination
(N=28) :Figure 3 shows the distribution of percent of patients displaying the four possible
IKDC knee group grades. At follow-up, final grade was normal in 59.0% of patients and
nearly normal in 31.1%, resulting in a proportion of 90.1% of patients displaying knee
conditions within the two best categories. Only in one case the knee was rated as severely
abnormal: this may have been related to the occurrence of a marked fibroarthrosis.
Macroscopic assessment of the repair tissue (N=17). The mean repair score for this set of
patients, at a mean arthroscopy time from surgery of 12.2 months, was 10.7 (range 3–12).
Cartilage repair was found to be normal in 43.2% of the cases, and nearly normal in 54.1%
(20 cases, 9 of which scored 11). Thus, in 36 cases the cartilage repair was rated as
biologically acceptable. Only one case, associated to periosteal hypertrophy, was rated as
severely abnormal, having a biologically unacceptable appearance with significant
fissuring of the repair tissue and no integration with the surrounding cartilage. Biopsy
analysis (N=24).The majority of the biopsies (n =15/24) were rated as hyaline-like, five
cases as mixed tissue and four as fibrocartilage. Average second-look arthroscopy time
post-surgery for this subset of patients was 14.2 months. During second-look arthroscopy,
in the first 19 cases, a cartilage biopsy has been obtained from the center of the repaired
defect, 12 months after grafting: the arthroscopical views showed total scaffold
biodegradation, a significantly improved appearance of the tissue and uniform
cartilagineous resurfacing with good mechanical resistance to probe palpation, although
cartilage fibrillation and areas of uneven cartilage stiffness were visible in almost of the
cases. The morphological analysis of the newly formed cartilage tissue revealed an
heterogeneity throughout the repaired tissue: high proteoglycan content, limited presence
6
of collagen type I and abundant expression of collagen type II, a typical component of
hyaline extracellular matrix. The only two third look arthroscopy at 31ms. f.up completely
confirmed the features of the hyaline cartilage. Further work is required on the histological
examination of patients treated with Hyalograft C at longer time points (3 and 5 years) in
order to appreciate the quality of the reconstructed tissue and the maintenance of the
cartilage quality.
Adverse events: A total number of 6 adverse events was recorded. Intraarticular
adhesions were seen in 2 patients 12 months after surgery. One patient, treated for a
lesion on the medial femoral condyle, underwent medial meniscus surgery and tibial
osteotomy concurrently with Hyalograft C implantation. A marked fibroarthrosis was seen
on arthroscopic examination. The second case, treated for a patella lesion, had patella
alignment concomitant to the biopsy for chondrocyte procurement. The patient did not
comply with the recommended post-operative rehabilitation program and reported a
marked stiffness. Symptoms resolved after arthroscopic adhesiolysis in both cases. One
patient experienced significant knee catching and locking 12 months after implantation,
which resolved after arthroscopic excision. The other patient was asymptomatic. In this
case, the hypertrophy was seen incidentally, 24 months after implantation, at the time of a
reoperation for a traumatic anterior cruciate ligament rupture; in that occasion the
hyperthrophic tissue was removed. The remaining adverse events recorded were one
post-operative fever from the 1st to the 5th day post-op and a dehiscence of the osteotomy
wound in a patient who had osteotomy concurrently with Hyalograft C application. No graft
failures, defined as requiring a re-operation to remove the implant or re-implant it, or a
procedure that violates the subchondral bone to treat the defect, have been reported. All
the patients grafted with Hyalograft-C reported a normal post-operative period, with no
serious adverse event related to the application of the product. Is rather the rule that within
three months an important swelling of the knee linked to the inflammatory response to the
Hyalograft-C implantation: this is as important as the size of the reconstructed defect. At
the same way it fairly normal a temperature increasing up to 38-38.5° in the first postop: 9
ot of 46 cases of increased temperature (<39°) completely ceased within 7 days To avoid
adherences it foundamental passive movement by kinetec since 3 rd postop.: in my opinion
electromagnetic fields applications is useful in controlling inflammatory response and to
avoid further bleeding.
Efficacy results: evaluation by both clinicians and patients of overall knee condition were improved at 12 –month follow-up visit. Among knees with both baseline and
12 –month data clinician and patient evaluations increased from means of 3.1 and 3.2 (with 2 being poor and 4 being fair) to means of 7.6 and 7.2 (with 6 being good
and 8 being very good) at 12 m-month f.up visit. All knees with defect on all locations were improved from baseline at 12month follow-up visit based on the clinician
and patient evaluation. Improvement in overall conditions , as assessed by both clinician and patient evaluation at 12-months, was evident, on average, for both acute
and chronic defects; for defects of the medial and lateral femoral condyle, trochlea and patella. Patient reported symptomatology was improved at 12 ms. f.up visit:
pain, swelling, partial giving way and full giving way each improved by an average of at least 4.0 points, all on a 0 (severe) to 10 (normal) scale at the 12 –month
follow-up visit compared to baseline. Knee examination result improved at 12 month follow-up visit: the proportion of patients with joint line pain decreased from 89%
at the baseline visit to 22 % at 12-months . Patients with moderate to severe joint line decreased from 65% at base line to 10% at 12ms. f.u.. The presence of effusion
decreased from 73% of the knees at baseline to 19% at 12ms. The proportion of patients with moderate or severe effusion decreased from 33% at baseline to 10 % at
12 ms. Return to work improved at 12 month follow-up visit. The number of patients who reported being on workers compensation decreased by more than half, from
40% of patients at baseline to 10 % at 12ms.Among patients on workers compensation at th e time of biopsy the number of workdays missed in the month preceding
the visit decreased by two-third, from a mean of 36% at baseline to 2% at 12ms.
Safety results: an adverse event is defined as any undesiderable physical, psychological, or behavioural effect experienced by a patient that is associated with the
use of the product, whether or not considered product related: we didn’t find any clinically relevant complication/adverse event as hypertrophic change, treatment
failure, detachment/delamination, exacerbated Knee pain, patella malalignment, synovitys, infections or neurovascular damage. In one case we reported as relevant
adverse event adhesion/fibroarthrosis in a patient that didn’t underwent any rehabilitation care and didn’t came for any visit except at the 2 nd arthroscopic look: we
managed this complication by arthroscopic arthrolisis gaining the 75% of ROM. ; Other events we considered to be not clinically relevant complication /adverse event
were a one case of deep vein thrombosis that occurred at 5 month post grafting.
Discussion
Hyalograft® C, a hyaluronan-based scaffold for delivery of cultured autologous
chondrocytes, recently introduced in clinical practice, is showing promise for the treatment
7
of full-thickness cartilage defects and is finding growing interest in the orthopaedic
community with more than 1000 patients treated to date. The updated findings of a
recently set up patient registry, regarding 28 patients with a mean follow-up period of 18
months, have been reviewed and indicate that the vast majority of patients treated
improved when assessed for relief of symptoms, improvement of mobility, pain reduction
and quality of repaired cartilage tissue. Interestingly, when patient’s improvement was
further analysed taking into account the size of lesions and time from implantation, data
obtained suggest a positive trend with respect to both parameters, i.e. the larger the size
or the longer the follow-up time, the greater the improvement. The safety profile of the
treatment appears positive, with a limited number of adverse events reported. Advantages
of Hyalograft® C over the currently available ACI technique include ease of handling, the
possibility to be tailored to fit the defect and to be delivered by a minimally invasive
technique, including arthroscopy (15), thus significantly reducing surgical time and
morbidity. With this novel approach, no periosteal coverage is required to keep the graft in
place. The authors acknowledge that the patient’s series analysed here has no control
group and represents a retrospective case series as for as basal and pre-surgery data are
concerned, thus lacking the methodological strength of a prospective clinical study.
However, follow-up data are being prospectively collected, and will represent a valuable
starting point for the design of future clinical studies. Additional clinical data will be
required to confirm the findings reported here at longer time points. With the above
limitations in mind, the authors consider Hyalograft® C an effective treatment option for
large defects (>2 cm2), particularly for patients with high physical demands and in those
cases in which, regardless of the size and the patient’s demand, lesions did not respond to
alternative cartilage repair techniques.
CONCLUSIONS
For several decades, high tibial osteotomy (HTO) has been the treatment of choice for
osteoarthritis of the knee, especially in young and active subjects. A literature search in the
Medline database yielded more than 50 studies on follow up after HTO. Most studies
report positive effects in 60-90 percent of the cases. The main indication for HTO is pain
and angle deformity of the knee due to unicompartmental gonarthrosis. Most cases
reported in the literature have medial gonarthrosis with varus deformity of the knee, but
about 15 percent of the subjects have lateral gonarthrosis with valgus deformity. Two main
treatments have been available: closed/openwedge osteotomy and dome (vault)
osteotomy. Normally, the knee is overcorrected to 5-13 degrees of valgus in medial
gonarthrosis, and the opposite in cases of lateral gonarthrosis. This overcorrection is
important for the final result of the osteotomy (2,3). The biomechanical idea behind the
operation is a reduction of the load on the affected compartment of the knee. In recent
years, however, cadaver studies have revealed that the extremity alignment necessary to
unload the medial compartment of the knee is about 25 degrees, and that the hypothesis
on biomechanical unloading probably is seriously flawed . Another possible mechanism
may be reduction of the intraosseous pressure. The variables most often evaluated have
been general improvement, pain, and walking ability. Some studies examined more
specific aspects, such as, postoperative joint angles, joint space, radionuclide uptake,
basic gait and cartilage regeneration parameters.
In particular some studies have shown fibrous cartilage regeneration after HTO: this tissue
is able to resurface the exposed bone but lacks of the biomechanical properties of the
hyaline cartilage leading to the recurrence of the arthrosis.
Osteotomy with additional Pridie drilling or abrasioarthroplsty associated with continuous
passive motion have showed cartilage regeneration thicker and more stable, sometimes
8
covering all of the preexisting erosions in confront of groups without additional operative
arthroscopy” (Schultz W. and Gobel D. Knee Surg Sport Traumat Arthrosc 1997 7(1): 2936) “High tibial osteotomy with arthroscopic abrasion arthroplasty has shown to promote
(fibro)cartilage regeneration in osteoarthritic knee with eburnation”(Akizuki S. et AA
Arthroscopy 1997 Feb; 13(1): 9-17)
When osteoarthritis is severe, the usual teatment is replacement of the arthritic articular
surface with an artificial prosthesis. Total knee replacement is most commonly performed
in people over 60 ys. old. Treatment of younger patients (under the age of 55 ys) is more
troublesome, because the prostheses have a limited lifetime. Osteotomy concurrently at
traditional resurfacing techniques is able to delay for at least 5 ys UKA or TKA: our
approach should significative improve clinical, arthoscopical and hystological outcome.
Transplanted autologous chondrocytes and high valgus ostotomy could be a good answer
to the problem. “Complex and Salvage treatment cases (107) having adjuvant treatment
including valgus tibial (N=24) or tibial tubercle (N=15) osteotomies at the 2 ys. f.up have
shown statistically significant functional improvements and patients satisfaction at 24 ms.
for simple, complex and salvage categories is 60%, 70% and 90% respectively in Minas
cases serie(Minas T. Clin Orthop 2001 Oct; (391 suppl): S349-61)
Easy graft application, normal postop. with discharge permitted on 3rd day after surgery,
with complete pain relief within four months, good or excellent joint functionality recovery
into 6 ms., no serious adverse event correlated and excellent clinical results at 18ms
follow-up are the promising outcome of Hyalograft-C technique and HTO.
The histological study performed on the first cases reviewed at 12 and 36 ms. follow-up at
arthroscopic 2nd look not only confirm the possibility of surgical application of Hyalograft-C
without a periosteal coverage, but also clear the role of periosteum in the cartilage graft
remodelling, due to fact that the presence of type II precollagen and collagen since 4
months after grafting proves the patch stability after the implant without periosteum
application: the hystological results at 12 ms f.up proves the ongoing process of
remodelling of the implanted tissue into hyaline cartilage tissue as well as in the
specimens treated with classic autologous condrocyte transplantation, with the advantage
to not present the incorporated remnants of periosteal tissue characteristic for all the
analysed grafts (Peterson). This technique represent a step forward in the chapter of
cartilage treatment. Avoid of the use of periosteum flap enormously simplify the surgical
technique and the patient morbidity can be decreased reducing considerably the surgical
time and permitting mini-open surgery.
Further work is required on the histological examination of patients treated with HyalograftC at longer time points (more than 18ms); immunolocalization of collagen type I will help
understand process of fibrous vs hyaline cartilage maturation. Finally we need to verify the
results at 3 ys and 5 ys to appreciate the quality of the reconstruction and the
maintainance of cartilage quality (no degenerative changes?)
See file 9-10-11
References
Curl WW, Krome J, Gordon S, Rushing J, Smith BP, Poehling GG: Cartilage injuries: a review of 31,516 knee
arthroscopies. Arthroscopy 1997; 13:456-460
Farnworth L: Osteochondral defects of the knee. Orthopedics 2000; 23:146-157
Minas T and Nehrer S: Current concepts in the treatment of articular cartilage defects. Orthopedics 1997;
20:525-538
Alparslan L, Winalski SC, Boutin RD, Minas T: Postoperative magnetic resonance imaging of articular
cartilage repair. Seminars in musculoskeletal radiology 2001; 5: 345-363
9
Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L: Treatment of deep cartilage defects in
the knee with autologous chondrocyte transplantation. N Engl J Med 1994; 331:889–895
Peterson L, Minas T, Brittberg M, Nilsson A, Sjögren-Jansson E, Lindahl A: Two to 9-years outcome after
autologous chondrocyte transplantation of the knee. Clinl Orthop 2000; 374:212–234
Freed LE, Marquis JC, Nohria A, Emmanual J, Mikos AG, Langer R: Neocartilage formation in vitro and in
vivo using cells cultured on synthetic biodegradable polymers. J Biomed Mater Res 1993; 27:11–23
van Susante JL, Buma P, van Osch GJ, Versleyen D, van der Kraan PM, van der Berg WB, Homminga GN:
Culture of chondrocytes in alginate and collagen carriers gel. Acta Orthop Scand 1995; 66:549–556
Brun P, Abatangelo G, Radice M, Zacchi V, Guidolin D, Daga Gordini D, Cortivo R: Chondrocyte aggregation
and reorganization into three-dimensional scaffolds. J Biomed Mater Res 1999; 46:337–346
Campoccia D, Doherty P, Radice M, Brun P, Abatangelo G, Williams DF: Semisynthetic resorbable materials
from hyaluronan esterification. Biomaterials 1998; 19:2101–2127
Aigner J, Tegeler J, Hutzler P, Campoccia D, Pavesio A, Hammer C, Kastenbauer E, Naumann A: Cartilage
tissue engineering with novel nonwoven structured biomaterial based on hyaluronic acid benzyl ester. J
Biomed Mater Res 1998; 42:172–181
Grigolo B, Lisignoli G, Piacentini A, Fiorini M, Gobbi P, Mazzotti G, Duca M, Pavesio A, Facchini A: Evidence
for redifferentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAFF11):
molecular, immunohistochemical and ultrastructural analysis. Biomaterials 2002; 23:1187–95
Grigolo B, Roseti L, Fiorini M, Fini M, Giavaresi G, Aldini NN, Giardino R, Facchini A: Transplantation of
chondrocytes seeded on a hyaluronan derivative (HYAFF11) into cartilage defects in rabbits. Biomaterials
2001; 22:2417–24
Solchaga LA, Yoo JU, Lundberg M, Dennis JE, Huibregtse BA, Goldberg VM, Caplan AI: Hyaluronan-based
polymers in the treatment of osteochondral defects. J Orthop Res 2000; 18:773–780
Scapinelli R, Aglietti P, Baldovin M, Giron F, Teitge R: Biological resurfacing of the patella. Current Status.
Clinics Sports Med 2002; 21: 547-573
Marcacci M, Zaffagnini S, Kon E, Visani A, Iacono F, Loreti I: Arthroscopic autologous chondrocyte
transplantation: technical note. Knee Surg Sports Traumatol Arthrosc 2002; 10: 154-159
Zorzi C, Hyalograft C Clinical Study Group: 2000 Tissue Engineered cartilage grafting: preliminary clinical
data. ICRS Symposium, Gothenburg, Sweden 124
Schatz KD: Erste Erfahrungen Mit Matrixassistierter Knorpel-Zelltransplantation (Summary experiences with
autologous chondrocyte implantation) Arthritis Rheum (Munch ) 2001; 5:262–268
Schatz KD: Treatment of cartilage lesions using expanded cartilage cells seeded on a three dimensional
fibrous scaffold based on benzylic ester of hyaluronic acid – preliminary clinical results. Osteoarthritis
Cartilage 2001: 9 suppl B PA32 S29
Pavesio A, Abatangelo G, Borrione A, Brocchetta D, Hollander AP, Kon E, Torasso F,
Zanasi S and Marcacci M: Hyaluronan-based scaffolds (Hyalograft® C) in the treatment of knee cartilage
defects: preliminary clinical findings, in press in “Novartis Foundation Symposium No.249 'Tissue engineering
of cartilage and bone', published by John Wiley and Sons, Chichester, UK"
ICRS
Cartilage
Injury
Evaluation
http://www.cartilage.org/Evaluation_Package/ICRS_Evaluation.pdf
Package
2000
Rabin R, de Charro F: EQ-5D: a measure of health status from the EuroQol Group. Ann Med 2001; 33:337–
343
Bauer,G.C,Insall,J and Koshino T. Tibial osteotomy in gonathrosis.J.Bone and Joint Surg.51A:15451563,1969.
Bourne R.B,Finlay J.B,Papadopoulos P,Rorabeck C.H,and Andreae P. In vitro strain distribution in the
proximal tibia.Effect of varus-valgus loading in the normal and osteoathritic knee.Clin.Orthop.188:285292,1984.
Chao
E.Y.S:Biomechanics
of
high
tibial
osteotomy.
American
Academy
of
10
Orthop.Surgeons.St.Louis,C.V.Mosby.1978.
Coventry M.B.Osteotomy of the upper portion of the tibia for degenerative arthritis of the knee.A preliminary
report.J Bone Joint Surg.47A:984-990,1965
Devas M.B.High tibial osteotomy for arthritis of the knee.A method specially suitable for the elderly.J.Bone
Joint Surg.51B:95-99,1969.
Gariepy R.Genu varum treated by high tibial osteotomy.J.Bone Joint Surg.46B:783,1964.
Harris W.R.and Kostuik J.P.High tibial osteotomy for osteoarthritis of the knee.J.Bone Joint Surg.52A:330336,1970.
Hernigou P,Medeviell D,Debeyre J and Goutallier D.Proximal tibial osteotomy with varus deformity.A ten to
thirteen year follow up study. J.Bone Joint Surg.69A:332-354,1987.
Holden D.L,James S.L,Larson R.L,and Slocum D.B.Proximal tibial osteotomy in patients who are fifty years
old or less.J.Bone Joint Surg.70A 977-982,1988.
Insall J,Shoji H,and Mayer V.High tibial osteotomy.A five years evaluation J.Bone Joint Surg.56A:13971405,1974.
Jackson J.P.Osteotomy for osteoarthritis of the knee.J.Bone Joint Surg.40B,826,1958.
Jackson J.P,and Waugh W.The technique and complications of upper tibial osteotomy.A review of 226
operations.J.Bone Joint Surg.56B:236-245,1974.
Maquet P.Valgus osteotomy for osteoathritis of the knee.Clin.Orthop.120:143,1976.
Morrey B.F.Upper tibial osteotomy for secondary osteoarthritis of the knee.J.Bone Joint Surg.71B:554559,1989.
Noyes F.R,Munns S.W,Andriacchi T.P,andMarschall M.T.The double varus and triple varus anterior cruciate
ligament insufficient knee:Gait analysis and surgical correction.Trans Am Orthop Soc Sports
Med.11:41,1985.
Odenbring S,Tjornstrand.B,Egund N,Hagstedt B,Hovelius L,Linstrand A,Luxhoj T and Svanstrom A.Function
after tibial osteotomy for medial gonarthrosis below age 50 years.Acta Orthop.Scand.:60,527-531,1989.
Puddu G,Cipolla M,Cerullo G and Scala A.Arthroscopic treatment of the flexed arthritic knee in active middle
age patients.Knee Surg.Sports Traumat.Arthroscopy 2:73-75,1994
Smillie J.S.Upper tibial osteotomy:In proceeding of the Scottish Orthopaedic Club.J.Bone Joint
Surg.43B:187,1961.
Volkman R.Osteotomy for knee joint deformity.Edimburgh Med.J.794, 1875.
11