Biologics

The problem is not new. A routine arthroscopic knee surgery is performed and an isolated Grade 4 cartilage is seen. So what is a surgeon to do? Certainly one could easily perform a microfracture but is the patient going to accept the often-prescribed 6 weeks of limited weight-bearing? Other options do exist, but once again, not all patients are accepting of a more invasive procedure with a prolonged rehabilitation period.

We thought we had an answer in the mid 1990s with the popularization of autologous chondrocyte transplantations (Carticel; Genzyme Corp, a Sanofi company, Cambridge, Massachusetts). There was a sense of excitement and theorthopedic community went biopsy crazy. Mandatory training was required, initially in Gothenburg, Sweden, and a new dawn of cartilage restoration was born. This excitement spilled over into other forms of cartilage treatments including Osteochondral Autograft Transfer Systems (OATS), with improved instrumentation and more options for the treatment of these cartilage lesions. This time period was the Renaissance Period of cartilage restoration: a period of excitement that led to the establishment of the International Cartilage Repair Society.

But as cartilage restoration became more popular, so did the amount of obstacles surgeons would encounter to be able to perform these procedures. Because of a paucity of literature describing the efficacy of these procedures, insurance companies were quick to describe the procedures as experimental, often refusing to approve the procedures or denying claims once performed.

While good results were eventually reported, some limitations remained. The procedure was expensive, two procedures, including an open arthrotomy was required, rehabilitation was slow and a high reoperation rate was reported. In addition, while this procedure is still being performed, it falls short of being the ultimate answer to isolated cartilage lesions of the knee.

What is the ideal method of cartilage repair? In a perfect world, all patients would be consented to routine arthroscopy and cartilage procedures as indicated (Figure 1). If an isolated lesion is seen, then the method of repair should be not only efficacious but should be performed arthroscopically, an off the shelf option, that can be performed at the same time as the diagnostic arthroscopy.

Over the last several years, we have seen a resurgence in cartilage restoration biologic options. DeNovo juvenile cartilage (Zimmer Inc, Warsaw, Indiana) has been introduced but does have its limitations. It is juvenile allograft cartilage that is prepared with a fibrin glue and placed currently as a second procedure. The lesion is seen at the time of diagnostic arthroscopy, lesion is sized, and how much of the cartilage to order is determined. Limits include not only the cost, but also the requirement of a second procedure, an arthrotomy, and lets not forget the need to bone graft the defect bed if significant subchondral bone loss has occurred.

Another recent advancement is the use of allograft cartilage plugs, Chondrofix, (Zimmer Inc) (Figures 2A, 2B). These are human allograft osteochondral plugs, irradiated for safety, have a long shelf life, and can be available as needed. Due to the radiation, the cartilage plugs may be disease-free, have been FDA approved, but there is a lack of long-term studies not only demonstrating efficacy but also long-term durability. Perhaps we are approaching the Holy Grail with biologic products such as this, but long-term acceptance will not occur until proper long-term studies are performed. Cost will remain an issue as well, since it is quite easy to place 3 to 4 plugs at one sitting and approach implant costs as high as a revision knee implant (Figure 3).

I am sad to say that the Holy Grail for biologic restoration of isolated cartilage lesions has yet to be found. We still do not have the perfect method for cartilage restoration at this time. While new attempts to restore cartilage remain in the pipeline, we must move away from pure animal studies, case reports, white papers, and small surgeon experience. Randomized controlled studies are needed to test these biologic advances, and finally find the ideal treatment for these isolated cartilage defects. We owe it to our patients to finally find the ideal treatment for these cartilage lesions.

Dr. Cushner is Editorial Review Board member of the journal; Chief of Orthopedics, Southside Hospital, Bay Shore, New York; and Director, Insall Scott Kelly, New York, New York.

Author’s Disclosure Statement: The author wishes to report that he will be a Speaker Bureau for Zimmer, Inc.

Am J Orthop. 2013;42(5):206-207. Copyright Frontline Medical Communications Inc. 2013. All rights reserved.

The problem is not new. A routine arthroscopic knee surgery is performed and an isolated Grade 4 cartilage is seen. So what is a surgeon to do? Certainly one could easily perform a microfracture but is the patient going to accept the often-prescribed 6 weeks of limited weight-bearing? Other options do exist, but once again, not all patients are accepting of a more invasive procedure with a prolonged rehabilitation period.

We thought we had an answer in the mid 1990s with the popularization of autologous chondrocyte transplantations (Carticel; Genzyme Corp, a Sanofi company, Cambridge, Massachusetts). There was a sense of excitement and theorthopedic community went biopsy crazy. Mandatory training was required, initially in Gothenburg, Sweden, and a new dawn of cartilage restoration was born. This excitement spilled over into other forms of cartilage treatments including Osteochondral Autograft Transfer Systems (OATS), with improved instrumentation and more options for the treatment of these cartilage lesions. This time period was the Renaissance Period of cartilage restoration: a period of excitement that led to the establishment of the International Cartilage Repair Society.

But as cartilage restoration became more popular, so did the amount of obstacles surgeons would encounter to be able to perform these procedures. Because of a paucity of literature describing the efficacy of these procedures, insurance companies were quick to describe the procedures as experimental, often refusing to approve the procedures or denying claims once performed.

While good results were eventually reported, some limitations remained. The procedure was expensive, two procedures, including an open arthrotomy was required, rehabilitation was slow and a high reoperation rate was reported. In addition, while this procedure is still being performed, it falls short of being the ultimate answer to isolated cartilage lesions of the knee.

What is the ideal method of cartilage repair? In a perfect world, all patients would be consented to routine arthroscopy and cartilage procedures as indicated (Figure 1). If an isolated lesion is seen, then the method of repair should be not only efficacious but should be performed arthroscopically, an off the shelf option, that can be performed at the same time as the diagnostic arthroscopy.

Over the last several years, we have seen a resurgence in cartilage restoration biologic options. DeNovo juvenile cartilage (Zimmer Inc, Warsaw, Indiana) has been introduced but does have its limitations. It is juvenile allograft cartilage that is prepared with a fibrin glue and placed currently as a second procedure. The lesion is seen at the time of diagnostic arthroscopy, lesion is sized, and how much of the cartilage to order is determined. Limits include not only the cost, but also the requirement of a second procedure, an arthrotomy, and lets not forget the need to bone graft the defect bed if significant subchondral bone loss has occurred.

Another recent advancement is the use of allograft cartilage plugs, Chondrofix, (Zimmer Inc) (Figures 2A, 2B). These are human allograft osteochondral plugs, irradiated for safety, have a long shelf life, and can be available as needed. Due to the radiation, the cartilage plugs may be disease-free, have been FDA approved, but there is a lack of long-term studies not only demonstrating efficacy but also long-term durability. Perhaps we are approaching the Holy Grail with biologic products such as this, but long-term acceptance will not occur until proper long-term studies are performed. Cost will remain an issue as well, since it is quite easy to place 3 to 4 plugs at one sitting and approach implant costs as high as a revision knee implant (Figure 3).

I am sad to say that the Holy Grail for biologic restoration of isolated cartilage lesions has yet to be found. We still do not have the perfect method for cartilage restoration at this time. While new attempts to restore cartilage remain in the pipeline, we must move away from pure animal studies, case reports, white papers, and small surgeon experience. Randomized controlled studies are needed to test these biologic advances, and finally find the ideal treatment for these isolated cartilage defects. We owe it to our patients to finally find the ideal treatment for these cartilage lesions.

Dr. Cushner is Editorial Review Board member of the journal; Chief of Orthopedics, Southside Hospital, Bay Shore, New York; and Director, Insall Scott Kelly, New York, New York.

Author’s Disclosure Statement: The author wishes to report that he will be a Speaker Bureau for Zimmer, Inc.

Am J Orthop. 2013;42(5):206-207. Copyright Frontline Medical Communications Inc. 2013. All rights reserved.

The problem is not new. A routine arthroscopic knee surgery is performed and an isolated Grade 4 cartilage is seen. So what is a surgeon to do? Certainly one could easily perform a microfracture but is the patient going to accept the often-prescribed 6 weeks of limited weight-bearing? Other options do exist, but once again, not all patients are accepting of a more invasive procedure with a prolonged rehabilitation period.

We thought we had an answer in the mid 1990s with the popularization of autologous chondrocyte transplantations (Carticel; Genzyme Corp, a Sanofi company, Cambridge, Massachusetts). There was a sense of excitement and theorthopedic community went biopsy crazy. Mandatory training was required, initially in Gothenburg, Sweden, and a new dawn of cartilage restoration was born. This excitement spilled over into other forms of cartilage treatments including Osteochondral Autograft Transfer Systems (OATS), with improved instrumentation and more options for the treatment of these cartilage lesions. This time period was the Renaissance Period of cartilage restoration: a period of excitement that led to the establishment of the International Cartilage Repair Society.

But as cartilage restoration became more popular, so did the amount of obstacles surgeons would encounter to be able to perform these procedures. Because of a paucity of literature describing the efficacy of these procedures, insurance companies were quick to describe the procedures as experimental, often refusing to approve the procedures or denying claims once performed.

While good results were eventually reported, some limitations remained. The procedure was expensive, two procedures, including an open arthrotomy was required, rehabilitation was slow and a high reoperation rate was reported. In addition, while this procedure is still being performed, it falls short of being the ultimate answer to isolated cartilage lesions of the knee.

What is the ideal method of cartilage repair? In a perfect world, all patients would be consented to routine arthroscopy and cartilage procedures as indicated (Figure 1). If an isolated lesion is seen, then the method of repair should be not only efficacious but should be performed arthroscopically, an off the shelf option, that can be performed at the same time as the diagnostic arthroscopy.

Over the last several years, we have seen a resurgence in cartilage restoration biologic options. DeNovo juvenile cartilage (Zimmer Inc, Warsaw, Indiana) has been introduced but does have its limitations. It is juvenile allograft cartilage that is prepared with a fibrin glue and placed currently as a second procedure. The lesion is seen at the time of diagnostic arthroscopy, lesion is sized, and how much of the cartilage to order is determined. Limits include not only the cost, but also the requirement of a second procedure, an arthrotomy, and lets not forget the need to bone graft the defect bed if significant subchondral bone loss has occurred.

Another recent advancement is the use of allograft cartilage plugs, Chondrofix, (Zimmer Inc) (Figures 2A, 2B). These are human allograft osteochondral plugs, irradiated for safety, have a long shelf life, and can be available as needed. Due to the radiation, the cartilage plugs may be disease-free, have been FDA approved, but there is a lack of long-term studies not only demonstrating efficacy but also long-term durability. Perhaps we are approaching the Holy Grail with biologic products such as this, but long-term acceptance will not occur until proper long-term studies are performed. Cost will remain an issue as well, since it is quite easy to place 3 to 4 plugs at one sitting and approach implant costs as high as a revision knee implant (Figure 3).

I am sad to say that the Holy Grail for biologic restoration of isolated cartilage lesions has yet to be found. We still do not have the perfect method for cartilage restoration at this time. While new attempts to restore cartilage remain in the pipeline, we must move away from pure animal studies, case reports, white papers, and small surgeon experience. Randomized controlled studies are needed to test these biologic advances, and finally find the ideal treatment for these isolated cartilage defects. We owe it to our patients to finally find the ideal treatment for these cartilage lesions.

Dr. Cushner is Editorial Review Board member of the journal; Chief of Orthopedics, Southside Hospital, Bay Shore, New York; and Director, Insall Scott Kelly, New York, New York.

Author’s Disclosure Statement: The author wishes to report that he will be a Speaker Bureau for Zimmer, Inc.

Am J Orthop. 2013;42(5):206-207. Copyright Frontline Medical Communications Inc. 2013. All rights reserved.

As physicians, we are always trying to keep up with the latest techniques and technology to provide the best possible care for our patients. However, history shows us that many of the “newest and greatest” devices have poorly understood, or maybe even, unknown consequences. You may remember the excitement over the Gortex ligament augmenta­tion device (LAD) for ACL reconstruction in the 1970’s or the thermal cap­sular shrinkage “heat probe” of the 1990’s. The orthopedic annals are littered with groundbreaking technologies that proved to be, at best, merely failures,or, at worst, dangerous to the patients we are trying to heal.

We are now in a time of rapidly changing technology and information overload, clogged with access to reams of information through our PDAs and the internet. Patients learn about new techniques and technology not from their physician, but from advertisements in the media or online. This dissemination of information without any real “filter” to verify accuracy and safety has heightened the burden on us, as surgeons, to be up to speed and critical of every “better mousetrap.” Patients may request or even demand a certain technique based on limited study of online discussions, chat rooms, or non–peer reviewed data. It is our obligation to “first, do no harm” even if the patient demands it.

How can we possibly provide the best for our patients and keep up with technol­ogy that may prove to be “the holy grail”? We must rely on well planned, peer-reviewed research studies that clearly analyze not only the positive results, but also the potential complications of new technology. In this month’s issue, E. Carlos Rodríguez-Merchán MD, PhD, (‘‘The Treatment of Cartilage Defects in the Knee Joint: Microfracture, Mosaicplasty, and Autologous Chondrocyte Implantation,’’click here) reviews the treatment of cartilage defects in the knee joint: comparing microfracture, mosaicplasty, and autologous chondrocyte implantation (ACI). However, he concludes that good level I evidence is lacking to show significant difference between any of the 3 commonly performed techniques. Does this mean that all of the procedures result in equal outcomes? No. Does this mean that we should abandon the more costly procedures, such as ACI? No. What Dr. Rodríguez-Merchán does is highlight the need for carefully designed level I studies to define the real outcomes, indications, and complications of our new technologies.

What is the holy grail in orthopedics? I would argue that the ability to take an easily obtained and prepared stem cell line and use the appropriate growth factors and chemical signals to cause the cells to differentiate into different tissue types (eg, bone, cartilage, ligament, etc.) rep­resents this holy grail. Think about all of the potential uses for this technology and it is easy to see the whole field of orthopedic surgery being transformed during my lifetime. Imagine being able to grow new cartilage or ligament tissue and direct the body’s response to these new tissues. However, with these pos­sibilities also come enormous risk.

One significant unpredicted outcome or inappropriate application could lead to huge consequences, terrible com­plications, bad publicity, and loss of patient-physician trust. Just imagine the late night television commercials and billboards advertising for the local law firm that “you may be entitled to com­pensation.” Or just imagine the uncer­tainty injected into the physician-patient relationship, “you aren’t going to put one of those recalled parts in me are you?” You may have followed the recent controversy over “pink slime,” the “lean, finely textured beef” added to processed hamburger patties. Although used for decades, the recent media coverage of beef filler has severely affected the pub­lic’s trust in the food industry. Can you imagine how a similar public relations nightmare over failed technology could affect the orthopedic industry?

I have often been guilty of complain­ing about the arduous task of getting new technology approved though the regulatory bodies in the United States, compared with the perceived progres­sive nature of the process in Europe. I do believe that we should have a streamlined process for some new tech­nology that may save lives, especially chemotherapy medications. However, a more diligent, and thorough process must be applied to new technology used for elective procedures, as in most orthopedic applications. Unfortunately, until sufficient safety data and good outcomes research is completed and analyzed, we must temper the enthusi­asm of doctors and patients alike.

Author's Disclosure Statement. The author reports no actual or poten­tial conflict of interest in relation to this article.

As physicians, we are always trying to keep up with the latest techniques and technology to provide the best possible care for our patients. However, history shows us that many of the “newest and greatest” devices have poorly understood, or maybe even, unknown consequences. You may remember the excitement over the Gortex ligament augmenta­tion device (LAD) for ACL reconstruction in the 1970’s or the thermal cap­sular shrinkage “heat probe” of the 1990’s. The orthopedic annals are littered with groundbreaking technologies that proved to be, at best, merely failures,or, at worst, dangerous to the patients we are trying to heal.

We are now in a time of rapidly changing technology and information overload, clogged with access to reams of information through our PDAs and the internet. Patients learn about new techniques and technology not from their physician, but from advertisements in the media or online. This dissemination of information without any real “filter” to verify accuracy and safety has heightened the burden on us, as surgeons, to be up to speed and critical of every “better mousetrap.” Patients may request or even demand a certain technique based on limited study of online discussions, chat rooms, or non–peer reviewed data. It is our obligation to “first, do no harm” even if the patient demands it.

How can we possibly provide the best for our patients and keep up with technol­ogy that may prove to be “the holy grail”? We must rely on well planned, peer-reviewed research studies that clearly analyze not only the positive results, but also the potential complications of new technology. In this month’s issue, E. Carlos Rodríguez-Merchán MD, PhD, (‘‘The Treatment of Cartilage Defects in the Knee Joint: Microfracture, Mosaicplasty, and Autologous Chondrocyte Implantation,’’click here) reviews the treatment of cartilage defects in the knee joint: comparing microfracture, mosaicplasty, and autologous chondrocyte implantation (ACI). However, he concludes that good level I evidence is lacking to show significant difference between any of the 3 commonly performed techniques. Does this mean that all of the procedures result in equal outcomes? No. Does this mean that we should abandon the more costly procedures, such as ACI? No. What Dr. Rodríguez-Merchán does is highlight the need for carefully designed level I studies to define the real outcomes, indications, and complications of our new technologies.

What is the holy grail in orthopedics? I would argue that the ability to take an easily obtained and prepared stem cell line and use the appropriate growth factors and chemical signals to cause the cells to differentiate into different tissue types (eg, bone, cartilage, ligament, etc.) rep­resents this holy grail. Think about all of the potential uses for this technology and it is easy to see the whole field of orthopedic surgery being transformed during my lifetime. Imagine being able to grow new cartilage or ligament tissue and direct the body’s response to these new tissues. However, with these pos­sibilities also come enormous risk.

One significant unpredicted outcome or inappropriate application could lead to huge consequences, terrible com­plications, bad publicity, and loss of patient-physician trust. Just imagine the late night television commercials and billboards advertising for the local law firm that “you may be entitled to com­pensation.” Or just imagine the uncer­tainty injected into the physician-patient relationship, “you aren’t going to put one of those recalled parts in me are you?” You may have followed the recent controversy over “pink slime,” the “lean, finely textured beef” added to processed hamburger patties. Although used for decades, the recent media coverage of beef filler has severely affected the pub­lic’s trust in the food industry. Can you imagine how a similar public relations nightmare over failed technology could affect the orthopedic industry?

I have often been guilty of complain­ing about the arduous task of getting new technology approved though the regulatory bodies in the United States, compared with the perceived progres­sive nature of the process in Europe. I do believe that we should have a streamlined process for some new tech­nology that may save lives, especially chemotherapy medications. However, a more diligent, and thorough process must be applied to new technology used for elective procedures, as in most orthopedic applications. Unfortunately, until sufficient safety data and good outcomes research is completed and analyzed, we must temper the enthusi­asm of doctors and patients alike.

Author's Disclosure Statement. The author reports no actual or poten­tial conflict of interest in relation to this article.

As physicians, we are always trying to keep up with the latest techniques and technology to provide the best possible care for our patients. However, history shows us that many of the “newest and greatest” devices have poorly understood, or maybe even, unknown consequences. You may remember the excitement over the Gortex ligament augmenta­tion device (LAD) for ACL reconstruction in the 1970’s or the thermal cap­sular shrinkage “heat probe” of the 1990’s. The orthopedic annals are littered with groundbreaking technologies that proved to be, at best, merely failures,or, at worst, dangerous to the patients we are trying to heal.

We are now in a time of rapidly changing technology and information overload, clogged with access to reams of information through our PDAs and the internet. Patients learn about new techniques and technology not from their physician, but from advertisements in the media or online. This dissemination of information without any real “filter” to verify accuracy and safety has heightened the burden on us, as surgeons, to be up to speed and critical of every “better mousetrap.” Patients may request or even demand a certain technique based on limited study of online discussions, chat rooms, or non–peer reviewed data. It is our obligation to “first, do no harm” even if the patient demands it.

How can we possibly provide the best for our patients and keep up with technol­ogy that may prove to be “the holy grail”? We must rely on well planned, peer-reviewed research studies that clearly analyze not only the positive results, but also the potential complications of new technology. In this month’s issue, E. Carlos Rodríguez-Merchán MD, PhD, (‘‘The Treatment of Cartilage Defects in the Knee Joint: Microfracture, Mosaicplasty, and Autologous Chondrocyte Implantation,’’click here) reviews the treatment of cartilage defects in the knee joint: comparing microfracture, mosaicplasty, and autologous chondrocyte implantation (ACI). However, he concludes that good level I evidence is lacking to show significant difference between any of the 3 commonly performed techniques. Does this mean that all of the procedures result in equal outcomes? No. Does this mean that we should abandon the more costly procedures, such as ACI? No. What Dr. Rodríguez-Merchán does is highlight the need for carefully designed level I studies to define the real outcomes, indications, and complications of our new technologies.

What is the holy grail in orthopedics? I would argue that the ability to take an easily obtained and prepared stem cell line and use the appropriate growth factors and chemical signals to cause the cells to differentiate into different tissue types (eg, bone, cartilage, ligament, etc.) rep­resents this holy grail. Think about all of the potential uses for this technology and it is easy to see the whole field of orthopedic surgery being transformed during my lifetime. Imagine being able to grow new cartilage or ligament tissue and direct the body’s response to these new tissues. However, with these pos­sibilities also come enormous risk.

One significant unpredicted outcome or inappropriate application could lead to huge consequences, terrible com­plications, bad publicity, and loss of patient-physician trust. Just imagine the late night television commercials and billboards advertising for the local law firm that “you may be entitled to com­pensation.” Or just imagine the uncer­tainty injected into the physician-patient relationship, “you aren’t going to put one of those recalled parts in me are you?” You may have followed the recent controversy over “pink slime,” the “lean, finely textured beef” added to processed hamburger patties. Although used for decades, the recent media coverage of beef filler has severely affected the pub­lic’s trust in the food industry. Can you imagine how a similar public relations nightmare over failed technology could affect the orthopedic industry?

I have often been guilty of complain­ing about the arduous task of getting new technology approved though the regulatory bodies in the United States, compared with the perceived progres­sive nature of the process in Europe. I do believe that we should have a streamlined process for some new tech­nology that may save lives, especially chemotherapy medications. However, a more diligent, and thorough process must be applied to new technology used for elective procedures, as in most orthopedic applications. Unfortunately, until sufficient safety data and good outcomes research is completed and analyzed, we must temper the enthusi­asm of doctors and patients alike.

Author's Disclosure Statement. The author reports no actual or poten­tial conflict of interest in relation to this article.