Ignite Creation Date:
2024-05-06 @ 8:25 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06376422
Status:
RECRUITING
Last Update Posted:
2024-04-19
First Post:
2024-04-12
Brief Title:
Sterile Allogeneic Spongioflex Allograft as Partial Meniscal Replacement After Incomplete Meniscal Loss
Sponsor:
Privatpraxis für Knie- und Schulterchirurgie
Organization:
Privatpraxis für Knie- und Schulterchirurgie
Study Overview
Official Title:
Sterile Allogeneic Spongioflex Allograft as Partial Meniscal Replacement After Incomplete Meniscal Loss an Investigator-initiated Low Interventional Trial
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this clinical trial is to learn if partial meniscal replacement can prevent or postpone total meniscal replacement in adult patients femalemale with partial meniscal loss The main questions it aims to answer are
Can partial meniscal replacement improve knee function
Can partial meniscal replacement preventpostpone total meniscal replacementknee prothesis Researchers will compare the results of the operated group with patients not willing to be operated but with partial meniscal loss to see if the operation improves knee function
Participants will be operated and have to attend follow-up visits with MRI after 6 months up to 5 years after surgery
Can partial meniscal replacement improve knee function
Can partial meniscal replacement preventpostpone total meniscal replacementknee prothesis Researchers will compare the results of the operated group with patients not willing to be operated but with partial meniscal loss to see if the operation improves knee function
Participants will be operated and have to attend follow-up visits with MRI after 6 months up to 5 years after surgery
Detailed Description:
The menisci consist of fibrocartilage They are partially laterally more than medially mobile parts of the joint surfaces and compensate for the incongruence of the femur and tibia They reduce the joint pressure on the tibial plateau and the femoral condyles and help to stabilize the joint Due to this biomechanical relevance the partial loss of the meniscus leads to arthritic changes in long term Suturing the torn meniscus is increasingly becoming the focus of knee surgery Degenerative torn menisci have a significantly poorer prognosis with regard to healing than traumatically torn menisci eg meniscus damage associated with a cruciate ligament tear
Indications for partial meniscus replacement are symptomatic degenerative and irreparable damage to the medial and lateral meniscus possibly with early osteoarthritis of the compartments as well as partial loss of the meniscus in the event of anterior knee instability in young active patients in which case simultaneous reconstruction of the anterior cruciate ligament should be performed A prerequisite for a good clinical result after partial meniscus replacement is a stable knee without malalignment in the coronal plane Partial meniscus replacement is not suitable in the case of axial deviation and knee instability patients older than 60 years advanced chondromalacia and degenerative changes in the affected compartment an extension deficit of more than 3 compared to the opposite side or a knee flexion of less than 125 Inflammatory arthritis or synovial inflammation of the knee and a Body Mass Index BMI greater than 30 kgm² are additional exclusion criteria
Williams et al 2007 could show that 5 years after partial removal of the medial or lateral meniscus despite an excellent functional result 64 of patients showed medial and 33 lateral cartilage damage on magnetic resonance imaging MRI This study highlights the considerable delay with which the symptoms occur despite already detectable arthritic changes
Englund et al were able to show in a study that patients developed osteoarthritis significantly more frequently over a period of 30 months if they had meniscus damage than if they did not Englund et al detected tibiofemoral osteoarthritis in 27 of patients 15 years after partial meniscus removal compared to 10 in a control group that had not undergone surgery
In the case of incomplete meniscus loss where the peripheral rim is sufficiently intact defect filling is the only way to restore the lost substance and function of the meniscus In the past an implant made of bovine collagen Collagen Meniscus Implant CMI Stryker or an artificial meniscus made of polyurethane Actifit 2med was often used The CMI has been withdrawn from the market by the manufacturer so that no biological treatment alternative exists
Schenk et al were able to show in a recent study for the CMI consisting of bovine collagen that despite a significant improvement in pain and function the CMI is subject to a progressive shrinkage process over time The studies mentioned above make it clear that partial replacement of the meniscus is necessary if preservation by meniscus suturing is no longer possible to prevent or postpone arthritic changes
In the investigator-initiated study on which this application is based a novel implant made from demineralized allogenic human cancellous bone Spongioflex DIZG gGmbH Berlin is to be implanted into the meniscus defect of the recipient knee This transplant has sponge-like properties and therefore facilitates the ingrowth of cells from the surrounding meniscus The investigational medicinal product IMP Spongioflex is de-calcified and demineralized it is hard when dry but soft when wet In the knee the conditions are wet thus it stays soft It is pliable Fig1 and can be easily sutured
Figure 1 Spongioflex
The manufacturer Deutsches Institut für Zell-und Gewebeersatz DIZG gGmbH did a study of cell ingrowth on Spongioflex They describe that ingrowth of cells on Spongioflex was observed after 28 days and these cells do not ossify
Scotti et al summarizes 2013 the knowledge in respect to meniscal repair as follows
In the last decade striving for optimal restoration of meniscal tissue the orthopedic surgeons armamentarium has been enriched by the use of biocompatible meniscus scaffold and meniscal allograft transplantation However despite promising short-term results none of the current strategies have demonstrated regeneration of a functional long-lasting meniscal tissue and re-establishment of a proper knee homeostasis in the meniscectomised knee The rationale for using a cell-free biomaterial to replace part of the meniscus is based on repopulation of the scaffold by the host cells recruited from the synovium and the meniscal remnants and subsequent tissue ingrowth which renders this approach cell-based after implantation A mandatory prerequisite is the absence of both knee instability and malalignment
This section of the paper of Scotti et al describes exactly the need for a restoration of the meniscus Furthermore it defines exactly the features of a scaffold
A biomaterial used as scaffold for meniscus tissue engineering purposes should present many features In particular the ideal meniscal scaffold should be i cell-instructive promoting cell differentiation and proliferation if cell-seeded or cell migration if cell-free ii biomimetic mimicking architecture tribology and mechanical features of the native meniscus iii resilient and resistant to withstand mechanical forces acting in the joint while cells produce extra cellular matrix ECM iv biocompatible not evoking any foreign-body reaction also with its degradation products v slowly biodegradable allowing to be gradually replaced by biologic tissue vi open with high porosity allowing diffusion of nutrients and catabolic substances and vii easy to handle to be sutured and to be implanted by the surgeon
Pereira et al describes that a meniscal implant either for partial or total replacement should
provide the biomechanical properties but also the biological features to replace the loss of native tissue Moreover these approaches include possibilities for patient-specific implants of correct size and shape
Spongioflex fulfils all these demands described by Dabaghi et al Scotti et al and Peirera et al and it can be adapted in size and shape and thus is in the moment the optimal choice for partial meniscal replacement
Dickerson et al describes that the scaffold must have a high fluid conductance concomitant with high porosity Porosity allows more rapid cell incorporation along the surface and through the thickness of the scaffold promoting integration with the host tissue The scaffold must guide cells to regenerate all four zones of the tissue structure
This is the case of Spongioflex it is porose and can guide cells Scotti et al proposes 2013 to use CMI for partial meniscal regeneration but this product is retracted from the market by now and they describe already the shrinking of the transplant Knee stability and an aligned knee are a requisite for the study proposed Dickerson et al shows that new fibrocartilage tissue is formed on the demineralized end of the allograft Results of Credille et al support these findings It will not be ossified again Smith et al describes that demineralized cancellous bone sponges are Food and Drug Administration-approved and commercially available products that have the potential to provide biologic and biomechanical augments for rotator cuff healing The sponge can act as a scaffold for cellular attachment and proliferation
Credille et al showed in a recent publication that a biphasic interpositional cancellous allograft BioEnthesis Sparta BioPharma Inc Madison NJ can be used for rotator cuff repair The allograft is a porous scaffold for endogenous biological factor migration and thus potentially address the lack of enthesis recapitulation at the rotator cuff repair interface while the demineralized layer supports soft-tissue ingrowth while acting as a sponge to hold bone marrow elements at the repair site
The group around Prof Moroder from the Charité has used Spongioflex for glenoid repair They describe that the transplant does not calcify again The glenoid is also no bony structure They used the same product in non-bone structures and could show successful restoration of the glenoid
Sundar et al describes that the use demineralized bone matrix increased fibrocartilage when used for augmentation of rotator cuff repair The used graft Spongioflex provides a scaffold for cell migration of meniscal cells from neighbouring parts of the meniscus The intended study will show that this kind of allograft is suitable for partial meniscal replacement because it allows cell migration and has enough porosity to allow fluid conductance 24 As described by Wildemann et al sufficient growth factors are remaining in the demineralized bone matrix Spongioflex to support new fibrocartilage formation Scotti et al underlines the importance of growth factors for meniscal regeneration
In summary from the literature it can be concluded that Spongioflex is an attractive scaffold for partial meniscal repair because it is fully biological it still has fibrocartilage inductive factors allows cell migration fluid conductivity resists biomechanical forces does not provoke immunoreactivity it is adaptable in size and can easily be sutured Partial meniscus replacement is an established surgical treatment for patients who have undergone partial meniscus removal to lead to the ingrowth of cells and the regeneration of meniscus-like tissue
The purpose of this investigator-initiated trial is to evaluate whether the novel graft can preventreduce the disadvantages of the previously used replacement materials and shows better results than the group of patients which were not operated Since there is currently no alternative made of biological material to this product this investigator-initiated trial is of great medical and economic importance The otherwise following arthrosis or knee prosthesis implantation TKA could be prevented or at least postponed Initial clinical results are promising
An important and sensitive parameter for assessing the postoperative function of the meniscus is the MRI image Genovese et al 2007 were able to show in a categorizationclassification which magnetic resonance image can be expected in the case of successful incorporation Several studies have shown that the known clinical knee scores Lysholm nternational Knee Documentation Committee IKDC Knee Injury and Osteoarthritis Outcome Score KOOS Visual Analogue Scale VAS pain improve significantly after successful ingrowth of the meniscus implant
Indications for partial meniscus replacement are symptomatic degenerative and irreparable damage to the medial and lateral meniscus possibly with early osteoarthritis of the compartments as well as partial loss of the meniscus in the event of anterior knee instability in young active patients in which case simultaneous reconstruction of the anterior cruciate ligament should be performed A prerequisite for a good clinical result after partial meniscus replacement is a stable knee without malalignment in the coronal plane Partial meniscus replacement is not suitable in the case of axial deviation and knee instability patients older than 60 years advanced chondromalacia and degenerative changes in the affected compartment an extension deficit of more than 3 compared to the opposite side or a knee flexion of less than 125 Inflammatory arthritis or synovial inflammation of the knee and a Body Mass Index BMI greater than 30 kgm² are additional exclusion criteria
Williams et al 2007 could show that 5 years after partial removal of the medial or lateral meniscus despite an excellent functional result 64 of patients showed medial and 33 lateral cartilage damage on magnetic resonance imaging MRI This study highlights the considerable delay with which the symptoms occur despite already detectable arthritic changes
Englund et al were able to show in a study that patients developed osteoarthritis significantly more frequently over a period of 30 months if they had meniscus damage than if they did not Englund et al detected tibiofemoral osteoarthritis in 27 of patients 15 years after partial meniscus removal compared to 10 in a control group that had not undergone surgery
In the case of incomplete meniscus loss where the peripheral rim is sufficiently intact defect filling is the only way to restore the lost substance and function of the meniscus In the past an implant made of bovine collagen Collagen Meniscus Implant CMI Stryker or an artificial meniscus made of polyurethane Actifit 2med was often used The CMI has been withdrawn from the market by the manufacturer so that no biological treatment alternative exists
Schenk et al were able to show in a recent study for the CMI consisting of bovine collagen that despite a significant improvement in pain and function the CMI is subject to a progressive shrinkage process over time The studies mentioned above make it clear that partial replacement of the meniscus is necessary if preservation by meniscus suturing is no longer possible to prevent or postpone arthritic changes
In the investigator-initiated study on which this application is based a novel implant made from demineralized allogenic human cancellous bone Spongioflex DIZG gGmbH Berlin is to be implanted into the meniscus defect of the recipient knee This transplant has sponge-like properties and therefore facilitates the ingrowth of cells from the surrounding meniscus The investigational medicinal product IMP Spongioflex is de-calcified and demineralized it is hard when dry but soft when wet In the knee the conditions are wet thus it stays soft It is pliable Fig1 and can be easily sutured
Figure 1 Spongioflex
The manufacturer Deutsches Institut für Zell-und Gewebeersatz DIZG gGmbH did a study of cell ingrowth on Spongioflex They describe that ingrowth of cells on Spongioflex was observed after 28 days and these cells do not ossify
Scotti et al summarizes 2013 the knowledge in respect to meniscal repair as follows
In the last decade striving for optimal restoration of meniscal tissue the orthopedic surgeons armamentarium has been enriched by the use of biocompatible meniscus scaffold and meniscal allograft transplantation However despite promising short-term results none of the current strategies have demonstrated regeneration of a functional long-lasting meniscal tissue and re-establishment of a proper knee homeostasis in the meniscectomised knee The rationale for using a cell-free biomaterial to replace part of the meniscus is based on repopulation of the scaffold by the host cells recruited from the synovium and the meniscal remnants and subsequent tissue ingrowth which renders this approach cell-based after implantation A mandatory prerequisite is the absence of both knee instability and malalignment
This section of the paper of Scotti et al describes exactly the need for a restoration of the meniscus Furthermore it defines exactly the features of a scaffold
A biomaterial used as scaffold for meniscus tissue engineering purposes should present many features In particular the ideal meniscal scaffold should be i cell-instructive promoting cell differentiation and proliferation if cell-seeded or cell migration if cell-free ii biomimetic mimicking architecture tribology and mechanical features of the native meniscus iii resilient and resistant to withstand mechanical forces acting in the joint while cells produce extra cellular matrix ECM iv biocompatible not evoking any foreign-body reaction also with its degradation products v slowly biodegradable allowing to be gradually replaced by biologic tissue vi open with high porosity allowing diffusion of nutrients and catabolic substances and vii easy to handle to be sutured and to be implanted by the surgeon
Pereira et al describes that a meniscal implant either for partial or total replacement should
provide the biomechanical properties but also the biological features to replace the loss of native tissue Moreover these approaches include possibilities for patient-specific implants of correct size and shape
Spongioflex fulfils all these demands described by Dabaghi et al Scotti et al and Peirera et al and it can be adapted in size and shape and thus is in the moment the optimal choice for partial meniscal replacement
Dickerson et al describes that the scaffold must have a high fluid conductance concomitant with high porosity Porosity allows more rapid cell incorporation along the surface and through the thickness of the scaffold promoting integration with the host tissue The scaffold must guide cells to regenerate all four zones of the tissue structure
This is the case of Spongioflex it is porose and can guide cells Scotti et al proposes 2013 to use CMI for partial meniscal regeneration but this product is retracted from the market by now and they describe already the shrinking of the transplant Knee stability and an aligned knee are a requisite for the study proposed Dickerson et al shows that new fibrocartilage tissue is formed on the demineralized end of the allograft Results of Credille et al support these findings It will not be ossified again Smith et al describes that demineralized cancellous bone sponges are Food and Drug Administration-approved and commercially available products that have the potential to provide biologic and biomechanical augments for rotator cuff healing The sponge can act as a scaffold for cellular attachment and proliferation
Credille et al showed in a recent publication that a biphasic interpositional cancellous allograft BioEnthesis Sparta BioPharma Inc Madison NJ can be used for rotator cuff repair The allograft is a porous scaffold for endogenous biological factor migration and thus potentially address the lack of enthesis recapitulation at the rotator cuff repair interface while the demineralized layer supports soft-tissue ingrowth while acting as a sponge to hold bone marrow elements at the repair site
The group around Prof Moroder from the Charité has used Spongioflex for glenoid repair They describe that the transplant does not calcify again The glenoid is also no bony structure They used the same product in non-bone structures and could show successful restoration of the glenoid
Sundar et al describes that the use demineralized bone matrix increased fibrocartilage when used for augmentation of rotator cuff repair The used graft Spongioflex provides a scaffold for cell migration of meniscal cells from neighbouring parts of the meniscus The intended study will show that this kind of allograft is suitable for partial meniscal replacement because it allows cell migration and has enough porosity to allow fluid conductance 24 As described by Wildemann et al sufficient growth factors are remaining in the demineralized bone matrix Spongioflex to support new fibrocartilage formation Scotti et al underlines the importance of growth factors for meniscal regeneration
In summary from the literature it can be concluded that Spongioflex is an attractive scaffold for partial meniscal repair because it is fully biological it still has fibrocartilage inductive factors allows cell migration fluid conductivity resists biomechanical forces does not provoke immunoreactivity it is adaptable in size and can easily be sutured Partial meniscus replacement is an established surgical treatment for patients who have undergone partial meniscus removal to lead to the ingrowth of cells and the regeneration of meniscus-like tissue
The purpose of this investigator-initiated trial is to evaluate whether the novel graft can preventreduce the disadvantages of the previously used replacement materials and shows better results than the group of patients which were not operated Since there is currently no alternative made of biological material to this product this investigator-initiated trial is of great medical and economic importance The otherwise following arthrosis or knee prosthesis implantation TKA could be prevented or at least postponed Initial clinical results are promising
An important and sensitive parameter for assessing the postoperative function of the meniscus is the MRI image Genovese et al 2007 were able to show in a categorizationclassification which magnetic resonance image can be expected in the case of successful incorporation Several studies have shown that the known clinical knee scores Lysholm nternational Knee Documentation Committee IKDC Knee Injury and Osteoarthritis Outcome Score KOOS Visual Analogue Scale VAS pain improve significantly after successful ingrowth of the meniscus implant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None