1) Prof. Ivan Martin,
I was intrigued by your concept and indeed I understand the potential
impact it could have. I would be thrilled to hear about the results of
further clinical tests, possibly within a prospective, randomized trial,
controlled vs the microfracture without resurfacing.
Please let me know if you wish to further discuss any specific
detail/issue related to your fascinating idea.
Very best wishes,
Prof. Ivan Martin
University Hospital Basel, Institute for Surgical Research and Hospital Management
ZLF, Hebelstrasse 20, 4031 Basel - Switzerland
Tel: +41 61 265 2384, Fax: +41 61 265 3990
Articles by Ivan Martin
Bioreactor-based roadmap for the translation of tissue engineering strategies into clinical products.
Orderly osteochondral regeneration in a sheep model using a novel nano-composite multilayered biomaterial
In vitro and in vivo validation of human and goat chondrocyte labeling by GFP lentivirus transduction.
Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy.
Radiographic evaluation of frontal talar edge configuration for osteochondral plug transplantation.
In vitro characterization of immune-related properties of human fetal bone cells for potential tissue engineering applications.
Design of graded biomimetic osteochondral composite scaffolds.
Lumican inhibits collagen deposition in tissue engineered cartilage.
Tissue engineering for total meniscal substitution: animal study in sheep model.
Human articular chondrocytes culture.
Growth factors for clinical-scale expansion of human articular chondrocytes: relevance for automated bioreactor systems.
Identification of markers to characterize and sort human articular chondrocytes with enhanced in vitro chondrogenic capacity.
Modulation of chondrocyte phenotype for tissue engineering by designing the biologic-polymer carrier interface.
Visual histological grading system for the evaluation of in vitro-generated neocartilage.
Use of hydrodynamic forces to engineer cartilaginous tissues resembling the non-uniform structure and function of meniscus.
Osteochondral tissue engineering.
Cartilage tissue engineering for degenerative joint disease.
Expansion on specific substrates regulates the phenotype and differentiation capacity of human articular chondrocytes.
Bioreactor-based engineering of osteochondral grafts: from model systems to tissue manufacturing.
Engineering of osteoinductive grafts by isolation and expansion of ovine bone marrow stromal cells directly on 3D ceramic scaffolds.
Experimental and mathematical study of the influence of growth factors on the growth kinetics of adult human articular chondrocytes.
Effects of scaffold composition and architecture on human nasal chondrocyte redifferentiation and cartilaginous matrix deposition.
Age related changes in human articular chondrocyte yield, proliferation and post-expansion chondrogenic capacity.
Plasticity of clonal populations of dedifferentiated adult human articular chondrocytes.
Tissue-engineered composites for the repair of large osteochondral defects.
2) Rune Jakobsen
I read your presentation and discussion of your new method for treating osteoarthritic knees with great interest.
You have certainly identified a subgroup of patients that will benefit from a procedure other than a total or subtotal arthroplasty with the implied risk of infection or the unability to follow post-op rehab, if this procedure will provide them pain relieve and by this better (perceived) knee function.
To me the clear novelties of your procedure (as your already point out) are using hamstrings instead of commercially available scaffolds or fascia lata and being used in a population with mainly osteoarthritis rather than the traumatic cartilage/subchondral lesions.
It is also clear to me that the patients on which this procedure was undertaken was extremely well taken care of in terms of preoperative information and informed consent.
I do however to some extent object to labelling you new method “not research”. That is not because I do not think that you build a convincing case that this is a safe method on the basis of already published basic and clinical research. The procedure will more likely than not provide some pain relief, is less likely to get a postoperative infection and will not exclude the patient from a future total or partial knee arthroplasty. It is because I believe with that label this is more likely to end up as yet another case series or expert opinion in the orthopaedic literature instead of a well performed level I or II study that may help to change guidelines. In your series you provide proof of principle and also proof of safety (acknowledging that it is a small series). I acknowledge that RCTs in general and in this particular case maybe very difficult to perform but I do believe that the next step (and a feasible one) is (at least)
a prospective comparative study taking into account as many of the features of a good RCT (blinded reviewer, validated outcome scores, patient questionnaires, planned follow-up timepoints etc).
Thank you for letting me read about your work. I am more than happy to discuss the topic further. Please let me know if you find anything of the above unclear or if you disagree, discussions always clarify arguments,
Articles by Rune B. Jakobsen : Orthopaedic Center, Ullevaal University Hospital and Medical School, University of Oslo, 0407, Oslo, Norway, Email: email@example.com
An Analysis of the Quality of Cartilage Repair Studies - The Journal of Bone and Joint Surgery (American). 2005;87:2232-2239.
Clinical studies on posterior cruciate ligament tears have weak design
ISAKOS: Current Concepts: AN ANALYSIS OF THE QUALITY OF CARTILAGE REPAIR STUDIES—An Update
The Reproducibility and Repeatability of Varus Stress Radiographs in the Assessment of Isolated Fibular CL and Grade-III Posterolateral Knee Injuries
3) Kai Mithoefer
Hi Dr. Wheeless,
Thanks again for sending me your technique information. I think it is an interesting approach that combines well established surgical techniques to create an autologous fibrocartilage. You mention that you have performed it in 8 patients and I would encourage you to report this small series for example as a technical note in Arthroscopy. This would describe the technique but also provide some preliminary safety data. If the results are encouraging, you might be able to develop this further. My only concerns are that you are produceing a metaplastic fibrocartilage and that the durability of the fibrocartilage may be limited particularly in large defects. Also, using autograft adds morbidity and time to the procedure that could potentially be equally achieved with an off the shelf collagen implant and microfracture as used frequently in Europe. I would encourage you though to systematically look at this method as it
seems well thought out and practical. Ultimately you will need to have larger patient numbers and prospective randomized data to further support you initial promising results. I hope this feedback is helpful for you.
Best regards from Boston and Good luck,
Articles from Mithoefer: (Harvard Vanguard Medical Associates)
Chondral Resurfacing of Articular Cartilage Defects in the Knee with the Microfracture Technique. Surgical Technique
The Microfracture Technique for the Treatment of Articular Cartilage Lesions in the Knee
Clinical Efficacy of the Microfracture Technique for Articular Cartilage Repair in the Knee: An Evidence-Based Systematic Analysis
Emerging options for treatment of articular cartilage injury in the athlete
The role of macrophages in early healing of a tendon graft in a bone tunnel
Articular cartilage repair in athletes
High-impact athletics after knee articular cartilage repair: a prospective evaluation of the microfracture technique.
Functional outcome after acute compartment syndrome of the thigh.
Supracondylar Femoral Fracture After Arthroscopic Reconstruction of the Anterior Cruciate Ligament
The long-term effects of articular impaction.
Pigmented villonodular synovitis of the anserine bursa
4) Knutsen G
Dear Dr. Wheeless
Thank's for your mail. This is very interesting- and I believe this could be useful for these patients. I have also done enhanced microfracture using periost or the collagen membrane. The hamstring tendons are strong and may be a better option for the OA patients. You should present your technique and results at an upcoming conference. I would be very interested to hear more about your results.
Gunnar Knutsen MD, PhD
Consultant Orthopaedic Surgeon
University Hospital North Norway
9038 Tromsø Norway
Articles by Knutsen
A Randomized Trial Comparing Autologous Chondrocyte Implantation with Microfracture. Findings at Five Years J of Bone Joint Surg (Am). 2007;89:2105-2112
Arthroscopic assessment of cartilage repair: a validation study of 2 scoring systems.Arthroscopy. 2005 Dec;21(12):1462-7.
A clinical review of cartilage repair techniques. J Bone Joint Surg Br. 2005 Apr;87(4):445-9
Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial.J Bone Joint Surg Am. 2004 Mar;86-A(3):455-64
Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. J Bone Joint Surg Am. 2003 Dec;85-A(12):2487-8;
Paper #123 Autologous chondrocyte implantation versus microfracture
Treatment of focal cartilage injuries in the knee. Tidsskr Nor Laegeforen. 1998 Jun 20;118(16):2493-7.
Letter to the editor. Randomized Trial Comparing Autologous Chondrocyte Implantation with Microfracture. A randomized trial
comparing ACI with microfracture. Findings at five years. J Bone Joint Surg Am. 2007 Oct;89(10):2105-12.
excuse the late answer, however presently, I am on vacation.
I have read your method. Basically it is an interesting method of the treatment heavy Osteoarthrosis for which a TKA is not considered. I have carried out in the past likewise arthroplasty / Chondroplasty with periosteal flaps.
Basically this effect stopped only after a few years. The regenerated tissue was very bad under biomechanical aspects. After about 3 years the state was again as well as before. Then I have dealt more than 10 years at the university with different cell types in the feld of cartilage regeneration. I can say to you, no fibrocytes from tendon, no blood cells, no chondrocytes and no stem cells repair a hard osteoarthritic knee. With your method a soft fibrous tissue cover the free laying bone. The patients profit a time because no more collagen type II is rubbed off any more and therefore, no more swelling and effusion would be observed.
In addition, the sensitive to pain bone is covered for a certain time. It would be great if you had done clinical re-examinations with MRI. These data would interest me very much. As an individual concept to the treatment from young patients with are not able to get a TKA I can
Articles by Steinwachs (Head of Orthobiologics and Cartilage Repair, Schulthess Clinic, Germany - see profile)
Marrow stimulation techniques
Cartilage Repair – Autologous Chondrocyte Transplantation and Autologous Matrix – induced Chondrogenesis
New technique for cell-seeded collagen-matrix-supported autologous chondrocyte transplantation
Characteristic complications after autologous chondrocyte implantation for cartilage defects of the knee joint
[Current treatment for cartilage damage in the patellofemoral joint]
Autologous chondrocyte implantation for the treatment of retropatellar cartilage defects: clinical results referred to defect localisation.
Technical note: the "double eye" technique as a modification of autologous chondrocyte implantation for the treatment of retropatellar cartilage defects.
Autologous chondrocyte implantation for the treatment of large full-thickness cartilage lesions of the knee.
Classification of graft hypertrophy after autologous chondrocyte implantation of full-thickness chondral defects in the knee.
Autologous chondrocyte implantation in chondral defects of the knee with a type I/III collagen membrane: a prospective study with a 3-year follow-up.
Importance of sports in cartilage regeneration after autologous chondrocyte implantation: a prospective study with a 3-year follow-up.
[Operative treatment of cartilage lesions in the knee joint]
Is microfracture of chondral defects in the knee associated with different results in patients aged 40 years or younger?
Results after microfracture of full-thickness chondral defects in different compartments in the knee
[Indications and implementation of recommendations of the working group "Tissue Regeneration and Tissue Substitutes" for (ACT)]
[Combinations of different cartilage resurfacing techniques]
The operative treatment of full thickness cartilage defects in the knee joint with autologous chondrocyte transplantation.
[Clinical and cell biology aspects of autologous chondrocytes transplantation]
Articular cartilage regeneration techniques
6) Hoemann CD
Dear Dr. Wheeless,
Your article on the internet is interesting and in fact timely since I am right now at the Miami airport, on my way home from the International artilage Repair Society meeting, 2009. I saw many presentations on the techniques you described (AMIC, chondroguide, TrueFit, ChondroCelect, etc), and I must admit that as a basic scientist, the evidence that these products have clinical benefit over surgical techniques alone is disappointing. There are no published randomized studies examining the effect of these scaffolds or cells on repair, and the patient
improvement is often described by the physician as "superior", while admitting that the patients never re-gain their activity levels or lifestyle scores the same as what they had prior to injury.
Chitosan-GP/blood implants, have recently been tested in a clinical trial in Canada and Europe with 80 patients, and these data are currently being analyzed out to a 1 year post-operative repair point (results should be completed by summer 2010). The next plan it to initiate a US study. This said, it is becoming more clear with time that the knee conditions are quite complex, and there is not going to be a one-for-all implant solution; our implant is intended for use in focal lesions and possibly OCD, in the condyle. I believe that microfracture with our implant
will give a satisfactory result for many patients. There is however a lot of dogma concerning the (unproven) efficacy of cell-based products (from what I saw at this meeting), but these techniques, even if they are working, are costly and not part of our Canadian health care system algorithm.
I hope I have answered some of your questions, good luck in your practice.
Dr. Caroline Hoemann, PhD
Dept Génie Chimique
Inst. Biomedical Engineering
CP6079 Succ Centre-ville
Montréal, QC H3C 3A7 Canada
Articles by Homann
Effect of chitosan particles and dexamethasone on human bone marrow stromal cell osteogenesis and angiogenic factor secretion.
Neutrophils exhibit distinct phenotypes toward chitosans with different degrees of deacetylation: implications for cartilage repair.
Drilling and microfracture lead to different bone structure and necrosis during bone-marrow stimulation for cartilage repair.
Meniscus structure in human, sheep, and rabbit for animal models of meniscus repair.
At-line quantification of bioactive antibody in bioreactor by surface plasmon resonance using epitope detection.
Fibronectin, vitronectin, and collagen I induce chemotaxis and haptotaxis of human and rabbit mesenchymal stem cells in a standardized transmembrane assay.
Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects.
The potential of chitosan-based gels containing intervertebral disc cells for nucleus pulposus supplementation.
Aged bovine chondrocytes display a diminished capacity to produce a collagen-rich, mechanically functional cartilage extracellular matrix.
Molecular and biochemical assays of cartilage components.
A multivalent assay to detect glycosaminoglycan, protein, collagen, RNA, and DNA content in milligram samples of cartilage or hydrogel-based repair cartilage.
7) Ernst B. Hunziker
Dear Dr. Wheeless
Thank you again for your e-mail. I have read your article in the Orthopaedic Specialist of North Carolina that you pointed out to me. Your concept to enhance microfractures seems to be interesting and new. As you point out in this article, there are many people who are trying to enhance microfracture using other types of scaffolds. The main drawback of microfracture is, as you know, the age. The stem cells that are stimulated to proliferate and differentiate are reduced in number in the aging population and are loosing their potential to differentiate significantly when aging, so that the procedure is useful only for young people up to the age of roughly 50 years. If we had available a method that could enhance microfracture healing in the elderly population, that would be a real advance. If you have any preclinical data available, it would be interesting to analyze them. From the report in the North Carolina Orthopaedic Specialist, I cannot comment more specifically, since there is no solid scientific data presented. However, the concept is interesting and worthwhile to pursue and it should be put on a solid scientific basis, so that we will be able to analyze clearly a potential advantage. I wish you good luck in your endeavours and thank you again for pointing out this activity of yours to me.
With kind regards, Ernst B. Hunziker
Center of Regenerative Medicine for Skeletal Tissues Department of Clinical Research, University of Bern Murtenstrasse 35, P.O. Box 54, 3010 Bern (Switzerland) (firstname.lastname@example.org)
8) Mitsuo Ochi
Dear Dr. Wheeless,
Thank you for your interest on our procedure. Your idea to use autogeneous soft tissue for cartilage defect in order to buy time is another interesting approach. I had a similaridea in1991. There are several papers including ours to use allogeneic meniscus to repair a cartilage defect. Arthroscopy 11:185-193 1995 Treatment of articular defects with meniscal allografts in a rabbit knee model. The problem is the border area between normal cartilage and grafted soft tissue that can not be well integrated.
Articles by Ochi (Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi, Hiroshima, Japan. email@example.com)
9) Myron Spector
Dear Dr. Wheeless,
Thank you again for sending the informative write-up of your concept of “autologous
hamstring resurfacing arthroplasty.” While it would never have struck me to take the approach
that you have, I can see now how useful it is to explore this resurfacing method. Let me also
say at the outset how much I appreciated your thoughtfully comprehensive documentation including
the review of the literature. I have still not had the time to go through your documentation as carefully
as I would like, but I wanted to respond to you as soon as possible.
Coincidently, we just completed a study that supports tendon resurfacing arthroplasty
(see attached paper accepted for publication in J. Orthop. Res.), although that is not what we
had in mind when we performed the study. While the investigation used caprine infraspinatus
tendon, we would expect the results to hold as well for human hamstring tendon.
The principal issue, in my mind, is the integration of the remodeling tendon into the
underlying bone (viz., development of a “Sharpey’s fibers attachment apparatus”). I believe
that it is likely that this will occur, but I don’t know if it will occur along the entire base of all
lesions. One of the obstacles to integration is the presence of lubricin. While it is desirable
(necessary) to have a lubricin layer on the articulating surfaces in joints, the presence of a
lubricin layer on the torn edges of tissues or on the surfaces of tissues that are brought together
in the joint (e.g., hamstring tendon and cartilage defect) can interfere with integrative binding (but
that’s another story).
We are engaged in several studies of resurfacing arthroplasty in a goat model, and
it would be interesting to include tendon resurfacing arthroplasty, but we do not have
sufficient funds to do so. In fact, I don’t think that I would even recommend doing an
animal study at this point. I think that it is best to continue with human trials, with formal
IRB -approved protocols including MRI, second-look arthroscopy, and opportunistic
biopsies. What we might have to offer you is assistive histological /immunohistochemical
evaluation of any biopsies, and depending on your results a satellite trial here in Boston
(perhaps at the VA).
Let me know if there is anything else that I can do.
Best of luck,
Myron Spector, Ph.D. -Professor of Orthopaedic Surgery (Biomaterials)
Harvard Medical School
-Senior Lecturer, MIT
-Director of Tissue Engineering
VA Boston Healthcare System
-Director of Orthopaedic Research Brigham and Women's Hospital VA Boston Healthcare System
150 S. Huntington Ave. MS 151 Boston, MA 02130
Off: +1 857 364-6639 Cell: +1 617 669-5244
11) James H. Lubowitz, MD
Congratulations on all your accomplishments and contributions to our field and to your patients.
Thank you for noting my article--the thesis was not arthroscopy "for" degenerative knees but
arthroscopic indications "in" degenerative knees, which I know you understand and intended
to state in the best possible spirit.
My feedback is that the technique you describe makes absolute sense; I was skeptical at first
(as will be many), but carefully read what you wrote; it is well presented. I would strongly suggest
you consider a RCT comparing this technique to non-surgical treatment and/or arthroplasty.
James H. Lubowitz, MD
1219A Gusdorf Rd.
Taos, NM 87571 USA
Assistant Editor-in-Chief, Arthroscopy: The Journal of Arthroscopic and Related Surgery
Editor-in-Chief, ISAKOS Newsletter
Director, Taos Orthopaedic Institute, Taos Orthopaedic Institute Research Foundation,
Taos Orthopaedic Institute Sportsmedicine Fellowship and Training Program
575 758 0009
fax 575 758 8736
11) David Hungerford
Sorry for the delay in this response. I was out of the country for 5 weeks and have been wading through the 650 emails
that awaited my return. You certainly have been thinking about this issue and your article is very informative. I have been
interested in this subject for the past 20 years, and have spent considerable monies trying to develop a solution. In our
labs we discovered that if one cultured Chondrocytes in a spinner flask they proliferated very rapidly without undergoing
first dedifferentiation to fibroblasts as occurs when they are cultured in a static medium. This was the first time that
Chondrocytes proliferation had ever been observed without dedifferentiation. We thought that this was a unique discovery
and formed a company called Chondros. We patented the concept and proceed to grow up cells with the idea of investing
autogenous mature Chondrocytes into a matrix for eventual implementation. Our timing couldn't have been worse.
Fundraising was extremely difficult and we were not able to raise the necessary funds to go forward. That's my background.
The concept was to deliver to the patient a more mechanically competent and mature biological implant that would be less
dependent on the patients response to the ACI method for example and this would also accelerate the rehab period.
One of the things that is missing from your report is the post-operative rehab period for your patients. Obviously the
tendon graft does have some physical properties probably similar to the implants that we were trying to create, but the
tendon graft still has to heal to the bone, and that would require a period of protected weight bearing, if not non-wt. bearing.
I also have some problem with your premise in the paragraph pasted below.
There is a subgroup of these patients that cannot have - or do not want - a total or partial joint replacement
(TJR). These patients note that they either do not want a TJR because of their health, because of the risks
associated with surgery, or because they are unwilling to perform the necessary postoperative therapy.
What some of these patients are asking for, is a simple surgery that gives them some pain relief (perhaps
30-50%) without the comorbidity of a knee replacement.
Certainly a medial uni has a very quick recovery with very little morbidity, and not much post-op therapy required. Is your
procedure done arthroscopically? What about the taking of the tendon graft. Is there no morbidity from that? What is your
post-op therapy. You have had two failures in your trial group, but I don't know what the 'n' factor is. I suspect that it is small
and this constitutes a significant percentage. "Avoiding a total knee replacement' is not really and end result. What has been
your result in terms of a functional score, activity level, pain level before and after, etc.
These are just a few 'off the cuff' comments which I hope are helpful. I have retired from surgery in the US. (I still do some in
the mission field), so I would not be in a position to participate in a trial, but that is the next logical step.
Original Text by Clifford R. Wheeless, III, MD.
Last updated by Clifford R. Wheeless, III, MD on Thursday, May 13, 2010 11:47 am