M. Delcogliano - Academia.edu (original) (raw)
Papers by M. Delcogliano
Midterm Results of a Combined Biological and Mechanical Approach for the Treatment of a Complex Knee Lesion
CARTILAGE, 2012
Objective: Complex fractures of the tibial plateau are difficult to treat and present a high comp... more Objective: Complex fractures of the tibial plateau are difficult to treat and present a high complication rate. The goal of this report is to describe a combined biological and mechanical approach to restore all morphological and functional knee properties. Methods: We treated a 50-year-old woman, who was affected by a posttraumatic osteochondral lesion and depression of the lateral tibial plateau with knee valgus deviation. The mechanical axis was corrected with a lateral tibial plateau elevation osteotomy, the damaged joint surface was replaced by a recently developed biomimetic osteochondral scaffold, and a hinged dynamic external fixator was applied to protect the graft and at the same time to allow postoperative joint mobilization. Results: A marked clinical improvement was documented at 12 months and further improved up to 5 years, with pain-free full range of motion and return to previous activities. The MRI evaluation at 12 and 24 months showed that the implant remained in s...
Technique of chondrocytes implantation
The Knee Joint, 2012
ABSTRACT A biodegradable, hyaluronian-based biocompatible scaff old is used for autologous chondr... more ABSTRACT A biodegradable, hyaluronian-based biocompatible scaff old is used for autologous chondrocyte implantation (ACI) for the treatment of articular cartilage lesions. This procedure consists of two steps: the fi rst one is an arthroscopic biopsy of healthy cartilage for chondrocyte cell culture. After 6 weeks, the bioengineered tissue obtained can be implanted trough a mini-open procedure or arthroscopic technique.
Tissue Engineering in the Treatment of Osteochondral Defects
A tissue engineering-based approach has become a possible solution for the treatment of chondral ... more A tissue engineering-based approach has become a possible solution for the treatment of chondral lesions. Actually, autologous chondrocytes seeded on biodegradable scaffolds for cell proliferation were successfully developed. However, these techniques promote cartilaginous but not bony regeneration. Therefore a new experimental approach involving mesenchymal stem cells (MSC) has been introduced. A 31-year-old man affected by massive osteonecrosis of the right femoral head was selected to begin this study. The MSC were isolated from the bone marrow harvested from the patient’s iliac crest. After a 3-week monolayer expansion, cells were seeded and cultured onto hyaluronan-based three-dimensional scaffolds and DBM spongy chips, used to regenerate the cartilaginous and the bony portion, respectively. After a 2-week cultivation, constructs were implanted inside the osteochondral defect using the transtrochanteric approach under arthroscopic control. The patient underwent clinical, X-ray and MRI control during the first 6 months after operation. Pluripotent MSC may be a promising strategy for osteochondral defect reconstruction due to their capacity to differentiate in vivo along chondrocytic and osteoblastic lineages. This ability, combined with two different kinds of three-dimensional scaffolds, permits simultaneous bone and cartilage tissue regeneration. The preliminary results are encouraging but a more precise judgement of the effectiveness of this method requires longer follow-up.
Tissue Engineering for Meniscal Regeneration
Introduction: Total meniscectomy can cause cartilage degeneration and osteoarthritis. The healing... more Introduction: Total meniscectomy can cause cartilage degeneration and osteoarthritis. The healing capacity of the meniscus is limited. Bioengineered meniscus can be a valid therapeutic option. Within the framework of the European Project MENISCUS, a pilot animal study was conducted to evaluate surgical technique, critical defect size, implant ingrowth and postoperative mobilization using a meniscus replacement device. Materials and Method: Six sheep were operated on their right stifle joints. 3 sheep received a total meniscus replacement with a 3D biomaterial fixed with sutures. Additionally, controls without implant were operated. The sheep were sacrificed and evaluated clinically and histologically after 6 weeks. Results: All implants showed excellent adhesion to the capsule and a good ingrowth at the periphery and the horns. Tissue formation was confirmed histologically. Conclusions: Tissue ingrowth of the implant was demonstrated. The promising results concerning tissue formation and its meniscus like properties will have to be confirmed in future long-term studies.
Rehabilitation for scaffolds versus classical ACI
Utilization of platelet-derived growth factors for the treatment of cartilage degenerative pathology
Osteoarthritis and Cartilage, 2007
Purpose: To evaluate the safety and performance of BioCart™II, a autologous chondrocytes, in the ... more Purpose: To evaluate the safety and performance of BioCart™II, a autologous chondrocytes, in the treatment of symptomatic chronic cartilage defects of the femoral condyle. Methods and Materials: 8 patients (7m, 1w) with an average age of 30,4 years suffering from cartilage defects of the medial femoral condyle (average size 4,6cm 2) were included in the study. Cartilage biopsies were taken arthroscopically, the cells were expanded with autologous serum. BioCart™II was implanted after 3 to 6 weeks. The patients were evaluated after 2, 6, 12 weeks, 6 and 12 months. Results: No serious adverse events occurred. 5 patients developed effusion, which resolved in all cases. The blood parameters were normal, there were no allergic reactions or problems of biocompatibility. After 12 months the subjective IKDC was improved postoperatively (p=0.0003; p=0.0001). The objective IKDC was implant hypertrophy in 4 patients, an intact cartilage and bone interface in 7 patients and a small subchondral edema in 4 patients. Conclusions: BioCart™II implantation was tolerated very well in treated patients with no indication for any potential allergic reaction or any impaired biocompatibility. The clinical outcome demonstrated both by MRI and clinical function scoring proved very positive with reduction in pain, improvement in patients' morbidity and good 22.5 Arthroscopic mosaicplasty technique for cartilage knee lesions. Magnetic resonance observation of cartilage repair tissue (MOCART) at a minimum 7 years follow-up.
Osteoarthritis and Cartilage, 2007
This study had the dual aims of establishing a multisite ovine model of articular cartilage injur... more This study had the dual aims of establishing a multisite ovine model of articular cartilage injury repair, whilst also arthroscopy (LSCA) for the postoperative histological assessment of cartilage repair. Methods and Materials: Defects (AE6mm) were created in the trochlea and medial femoral condyle of twenty-one sheep randomised into untreated controls, matrix-induced autologous chondrocyte implantation (MACI[Ò]), or unseeded MACI treatment, then further divided into 8, 10, and 12 week time points. Repair outcomes were examined using LSCA, routine histology, macroscopic ICRS evaluation, magnetic resonance imaging (MRI), and tissue stiffness testing. Interobserver variability and score system correlation was conducted to validate system reliability in assessing cartilage repair. Results: Assessment of MACI treatment by LSCA, MRI, histology, and macroscopic IRCS grading, illustrated improvement in repair compared to controls across all modalities. Additionally, MACI repair resembled native articular cartilage in early-stage remodeling histologically, but the stiffness of the MACI repair was inferior to the native tissue. Interobserver analysis of the blinded LSCA scoring validated our scoring protocol, with almost perfect agreement illustrated (ICC=0.9201). Furthermore, Pearson correlation analysis demonstrated that LSCA scoring correlated (P<0.05) to both MRI and ICRS grading. Conclusions: The assessment of cartilage repair has been primarily limited to macroscopic assessment, variable MRI, or destructive biopsy. The development of non-destructive LSCA cartilage repair assessment will facilitate reliable, high resolution, longterm monitoring of treated lesions in both experimental animal models and clinical patients, by obviating the need for destructive mechanical biopsy.
Treatment of Large Knee Osteochondral Lesions With a Biomimetic Scaffold: Results of a Multicenter Study of 49 Patients at 2-Year Follow-up
The American Journal of Sports Medicine, 2014
Background: Osteochondral knee lesions represent a challenging condition encountered by orthopaed... more Background: Osteochondral knee lesions represent a challenging condition encountered by orthopaedic surgeons. A variety of methods have been developed to repair articular cartilage defects. However, these techniques are limited by donor site morbidity or by the requirement for a staged procedure. Purpose: To assess the effectiveness of a biomimetic osteochondral scaffold for the treatment of large osteochondral knee lesions. Study Design: Case series; Level of evidence, 4. Methods: From 2009 to 2011, a total of 49 patients affected by isolated large osteochondral knee lesions (mean [± SD] size, 4.35 ± 1.26 cm2) were treated with the biomimetic scaffold. Patients were evaluated using the International Knee Documentation Committee (IKDC), Tegner, and visual analog scale (VAS) pain scores, as well as magnetic resonance imaging (MRI) up to 3-year follow-up. The MOCART (magnetic resonance observation of cartilage repair tissue) score was performed to analyze different variables. Biopsies were carried out in 5 patients. Four of the 5 second-look arthroscopies and biopsies were performed on patients with failed results because of ethical issues. Results: The mean IKDC subjective score increased significantly from 45.45 ± 19.29 preoperatively to 70.86 ± 18.08 at 1-year follow-up and to 75.42 ± 19.31 at 2-year follow-up ( P < .001). The IKDC objective score changed from 50% normal and nearly normal knees before treatment to 89.79% at the 2-year follow-up. There was a statistically significant improvement ( P < .005) in VAS score from the preoperative level (6.69 ± 1.88) to the 2-year follow-up (1.96 ± 2.47). Tegner scores increased ( P < .001) from the preoperative value (2.20 ± 0.67) to the 2-year follow-up (4.9 ± 1.73) without achieving preinjury level. A correlation was found between the IKDC subjective score and age ( P < .001, r = −0.497, ρ = −0.502). Patients affected by osteochondritis dissecans (OCD) achieved a statistically significantly better outcome ( P < .05). A subgroup of 19 competitive athletes showed a statistically significantly improvement ( P < .001) in the subjective IKDC (86.5 ± 13.2) compared with the nonathletic subpopulation (69.03 ± 19.41) at the 2-year follow-up. The MRI findings of 30 patients were available at 2-year follow-up: 70% showed complete filling of the lesion, 63.3% had an intact articular surface, and 86% had mild or no effusion. In all cases, in dual T2-weighted fast spin echo sequence, the repair tissue showed a hyperintensive signal with respect to the surrounding subchondral bone; however, no edema was observed. Conclusion: The study findings indicate that the biomimetic scaffold that was investigated is an off-the-shelf, cell-free, and cost-effective implant that can regenerate either cartilage or subchondral bone. The scaffold allows a 1-step surgical procedure that can be used for osteochondral lesions, OCD, and in some cases osteonecrosis.
Arthroscopy Techniques, 2013
The importance of the lateral meniscus in weight bearing, distribution of force, shock absorption... more The importance of the lateral meniscus in weight bearing, distribution of force, shock absorption, articular cartilage protection, proprioception, stabilization of the joint, and joint lubrication is well known. Surgeons currently agree on the importance of preserving the menisci. Different suture techniques have been standardized. These include outsidein, inside-out, and all-inside techniques. The all-inside technique can be used to repair lesions of the posterior horn of the lateral meniscus. However, this technique presents important disadvantages, such as the necessity for an accessory portal and a high risk of neurovascular damage. For these reasons, we have developed a technique in which a suture hook and a shuttle relay are used to pass the suture wire through the meniscal lesion of the posterior horn of the lateral meniscus with an all-inside technique, without the use of accessory portals and cannulas, with a standard 30 arthroscopic camera.
Osteoarthritis and Cartilage, 2007
Purpose: As a one-step arthroscopic procedure, microfracture is frequently considered to be techn... more Purpose: As a one-step arthroscopic procedure, microfracture is frequently considered to be technically easier and associated with less postoperative morbidity than autologous chondrocyte implantation (ACI), which involves both arthrotomy and arthroscopy. Safety was therefore assessed in patients with symptomatic cartilage lesions of the knee treated with either characterized chondrocyte implantation (CCI) using ChondroCelect ® or microfracture. Methods and Materials: CCI (n=57) was compared to microfracture (n=61) in patients with grade III-IV symptomatic cartilage defects of the femoral condyles in a Phase III prospective, multicenter, randomized controlled trial. Safety assessments included adverse events (AEs), physical examination, vital signs, hematology and clinical chemistry. Results: Similar proportions of patients experienced AEs in the CCI (88%) and microfracture (82%) groups; 67% and 59%, respectively,
Tissue Engineering Part A, 2008
Objective: The aim of the study was to investigate the use of a novel hyaluronic acid/polycaprola... more Objective: The aim of the study was to investigate the use of a novel hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Two different surgical implantation techniques in a sheep model were evaluated. Methods: Twenty-four skeletally mature sheep were treated with total medial meniscus replacements, while two meniscectomies served as empty controls. The animals were divided into two groups: cell-free scaffold and scaffold seeded with autologous chondrocytes. Two different surgical techniques were compared: in 12 animals, the implant was sutured to the capsule and to the meniscal ligament; in the other 12 animals, also a transtibial fixation of the horns was used. The animals were euthanized after 4 months. The specimens were assessed by gross inspection and histology. Results: All implants showed excellent capsular ingrowth at the periphery. Macroscopically, no difference was observed between cell-seeded and cell-free groups. Better implant appearance and integrity was observed in the group without transosseous horns fixation. Using the latter implantation technique, lower joint degeneration was observed in the cell-seeded group with respect to cell-free implants. The histological analysis indicated cellular infiltration and vascularization throughout the implanted constructs. Cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs. Conclusion: The current study supports the potential of a novel HYAFF/polycaprolactone scaffold for total meniscal substitution. Seeding of the scaffolds with autologous chondrocytes provides some benefit in the extent of fibrocartilaginous tissue repair.
Sports Medicine and Arthroscopy Review, 2008
In recent years, regenerative techniques, such as autologous chondrocyte implantation (ACI), have... more In recent years, regenerative techniques, such as autologous chondrocyte implantation (ACI), have emerged as a potential therapeutic option for the treatment of chondral lesions. However, the good results reported have to be weighed against the number of problems that can be observed with traditional ACI methods. To address these problems, the socalled second generation ACI techniques have been developed. Autologous chondrocyte transplantation on a 3-dimensional matrix was introduced in clinical practice from 1998 to 1999 and results at short to medium-term follow-up are well documented for different types of scaffolds. These techniques may be used for the treatment of large chondral lesions in the young, active population and highly competitive athletes, but long-term and randomized controlled studies will be needed to confirm reliability of these procedures.
Osteoarthritis and Cartilage, 2008
Osteoarthritis and Cartilage, 2007
Purpose: Evaluation of the occurrence and morphology of meniscus regrowth after complete medial r... more Purpose: Evaluation of the occurrence and morphology of meniscus regrowth after complete medial removal of the meniscus and its effect on the hyaline articular cartilage Methods and Materials: 32 NZW rabbits were used according to a protocol permitted by both, the Institutional and the Governmental Ethics Committee. All animals were male and skeletally mature as checked by standard x-ray. An open medial parapatellar approach was performed under sterile conditions. The medial meniscus was completely excised from the synovial junction. Particular care was taken at the posterior horn for complete separation from all 12 weeks. Macroscopic grading was performed in accordance with
Osteoarthritis and Cartilage, 2007
Autologous Chondrocyte Implantation (ACI) proposed by Brittberg in 1994 [1], involving re-implant... more Autologous Chondrocyte Implantation (ACI) proposed by Brittberg in 1994 [1], involving re-implantation of autologous cells that have been isolated from cartilage harvested from the patient and expanded in repair of focal articular cartilage lesions. A second-generation tissueengineering approach to cartilage repair was proposed, which uses a biodegradable three-dimensional scaffold for cell proliferation. This scaffold is entirely based on the benzylic ester of hyaluronic acid (HYAFF ® 11, Fidia Advanced Biopolymers Laboratories, Padova,
Osteoarthritis and Cartilage, 2007
Purpose: There is an increase in IL-1ß following joint injury which up-regulates catabolic enzyme... more Purpose: There is an increase in IL-1ß following joint injury which up-regulates catabolic enzymes breaking down the cartilage matrix. Little is known about the added effect of joint motion on matrix degradation. In this in vitro study we investigated proteoglycan/ GAG-release, an indicator for matrix breakdown , using a joint simulator applying dynamic loads and articular motion onto living cartilage explants in the presence of IL-1ß. Methods and Materials: were obtained from a local abattoir within 24 hours of slaughter. Nine cartilage disks were removed from the trochlea using a 14mm punch. After a 5 day pre-culture, 3 disks were tested in a joint simulator in controls. All tests were performed in serum-free, DMEM:F12 media for 3 hours. Medium was then individually collected and analyzed for the presence of proteoglycans/GAGs using the DMMB assay. Results: Cartilage explants cultured in the presence of IL-1ß (no release when compared to control. When motion was applied release when compared to control and a 2.6-fold increase when Conclusions: The combination of joint articulation and IL-1 ß resulted in the highest amount of proteoglycan/GAG release into the media. This preliminary evidence suggests that joint articulation following joint injury may be detrimental to the cartilage matrix.
Journal of Tissue Engineering and Regenerative Medicine, 2010
The present in vivo preliminary experiment is aimed at testing mechanical and biological behaviou... more The present in vivo preliminary experiment is aimed at testing mechanical and biological behaviour of a new nano-structured composite multilayer biomimetic scaffold for the treatment of chondral and osteochondral defects. The three-dimensional biomimetic scaffold (Fin-Ceramica Faenza S.p.A., Faenza-Italy) was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles, in two configurations, bi-and tri-layered, to reproduce, respectively, chondral and osteochondral anatomy. Chondral defects (lateral condyle) and deep osteochondral defects (medial condyle) were made in the distal epiphysis of the third metacarpal bone of both forelimbs of two adult horses and treated respectively with the chondral and osteochondral grafts. Both animals were euthanised six months follow up. The images obtained at the second look arthroscopy evaluation, performed two months after surgery, demonstrated good filling of the chondral and osteo-chondral defects without any inflammatory reaction around and inside the lesions. At the histological analysis the growth of trabecular bone in the osteochondral lesion was evident. Only in one case, the whole thickness of the osteochondral lesion was filled by fibrocartilaginous tissue. The formation of a tidemark line was evident at the interface with the newly formed bone. Newly formed fibrocartilaginous tissue was present in the area of the chondral defect. Initial alignment of the collagen fibres was recognisable with polarised light in both groups. The results of the present pilot study showed that this novel osteochondral and chondral scaffold may act as a suitable matrix to facilitate orderly regeneration of bone and hyaline-like cartilage.
Erratum: Novel nanostructured scaffold for osteochondral regeneration: pilot study in horses
Journal of Tissue Engineering and Regenerative Medicine, 2012
Journal of Orthopaedic Research, 2009
The objective of this article was to investigate the safety and regenerative potential of a newly... more The objective of this article was to investigate the safety and regenerative potential of a newly developed biomimetic scaffold when applied to osteochondral defects in an animal model. A new multilayer gradient nano-composite scaffold was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. In the femoral condyles of 12 sheep, 24 osteochondral lesions were created. Animals were randomized into three treatment groups: scaffold alone, scaffold colonized in vitro with autologous chondrocytes and empty defects. Six months after surgery, the animals were sacrificed and the lesions were histologically evaluated. Histologic and gross evaluation of specimens showed good integration of the chondral surface in all groups except for the control group. Significantly better bone regeneration was observed both in the group receiving the scaffold alone and in the group with scaffold loaded with autologous chondrocytes. No difference in cartilage surface reconstruction and osteochondral defect filling was noted between cell-seeded and cell-free groups. In the control group, no bone or cartilage defect healing occurred, and the defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed. The results of the present study showed that this novel osteochondral scaffold is safe and easy to use, and may represent a suitable matrix to direct and coordinate the process of bone and hyaline-like cartilage regeneration. The comparable regeneration process observed with or without autologous chondrocytes suggests that the main mode of action of the scaffold is based on the recruitment of local cells.
Midterm Results of a Combined Biological and Mechanical Approach for the Treatment of a Complex Knee Lesion
CARTILAGE, 2012
Objective: Complex fractures of the tibial plateau are difficult to treat and present a high comp... more Objective: Complex fractures of the tibial plateau are difficult to treat and present a high complication rate. The goal of this report is to describe a combined biological and mechanical approach to restore all morphological and functional knee properties. Methods: We treated a 50-year-old woman, who was affected by a posttraumatic osteochondral lesion and depression of the lateral tibial plateau with knee valgus deviation. The mechanical axis was corrected with a lateral tibial plateau elevation osteotomy, the damaged joint surface was replaced by a recently developed biomimetic osteochondral scaffold, and a hinged dynamic external fixator was applied to protect the graft and at the same time to allow postoperative joint mobilization. Results: A marked clinical improvement was documented at 12 months and further improved up to 5 years, with pain-free full range of motion and return to previous activities. The MRI evaluation at 12 and 24 months showed that the implant remained in s...
Technique of chondrocytes implantation
The Knee Joint, 2012
ABSTRACT A biodegradable, hyaluronian-based biocompatible scaff old is used for autologous chondr... more ABSTRACT A biodegradable, hyaluronian-based biocompatible scaff old is used for autologous chondrocyte implantation (ACI) for the treatment of articular cartilage lesions. This procedure consists of two steps: the fi rst one is an arthroscopic biopsy of healthy cartilage for chondrocyte cell culture. After 6 weeks, the bioengineered tissue obtained can be implanted trough a mini-open procedure or arthroscopic technique.
Tissue Engineering in the Treatment of Osteochondral Defects
A tissue engineering-based approach has become a possible solution for the treatment of chondral ... more A tissue engineering-based approach has become a possible solution for the treatment of chondral lesions. Actually, autologous chondrocytes seeded on biodegradable scaffolds for cell proliferation were successfully developed. However, these techniques promote cartilaginous but not bony regeneration. Therefore a new experimental approach involving mesenchymal stem cells (MSC) has been introduced. A 31-year-old man affected by massive osteonecrosis of the right femoral head was selected to begin this study. The MSC were isolated from the bone marrow harvested from the patient’s iliac crest. After a 3-week monolayer expansion, cells were seeded and cultured onto hyaluronan-based three-dimensional scaffolds and DBM spongy chips, used to regenerate the cartilaginous and the bony portion, respectively. After a 2-week cultivation, constructs were implanted inside the osteochondral defect using the transtrochanteric approach under arthroscopic control. The patient underwent clinical, X-ray and MRI control during the first 6 months after operation. Pluripotent MSC may be a promising strategy for osteochondral defect reconstruction due to their capacity to differentiate in vivo along chondrocytic and osteoblastic lineages. This ability, combined with two different kinds of three-dimensional scaffolds, permits simultaneous bone and cartilage tissue regeneration. The preliminary results are encouraging but a more precise judgement of the effectiveness of this method requires longer follow-up.
Tissue Engineering for Meniscal Regeneration
Introduction: Total meniscectomy can cause cartilage degeneration and osteoarthritis. The healing... more Introduction: Total meniscectomy can cause cartilage degeneration and osteoarthritis. The healing capacity of the meniscus is limited. Bioengineered meniscus can be a valid therapeutic option. Within the framework of the European Project MENISCUS, a pilot animal study was conducted to evaluate surgical technique, critical defect size, implant ingrowth and postoperative mobilization using a meniscus replacement device. Materials and Method: Six sheep were operated on their right stifle joints. 3 sheep received a total meniscus replacement with a 3D biomaterial fixed with sutures. Additionally, controls without implant were operated. The sheep were sacrificed and evaluated clinically and histologically after 6 weeks. Results: All implants showed excellent adhesion to the capsule and a good ingrowth at the periphery and the horns. Tissue formation was confirmed histologically. Conclusions: Tissue ingrowth of the implant was demonstrated. The promising results concerning tissue formation and its meniscus like properties will have to be confirmed in future long-term studies.
Rehabilitation for scaffolds versus classical ACI
Utilization of platelet-derived growth factors for the treatment of cartilage degenerative pathology
Osteoarthritis and Cartilage, 2007
Purpose: To evaluate the safety and performance of BioCart™II, a autologous chondrocytes, in the ... more Purpose: To evaluate the safety and performance of BioCart™II, a autologous chondrocytes, in the treatment of symptomatic chronic cartilage defects of the femoral condyle. Methods and Materials: 8 patients (7m, 1w) with an average age of 30,4 years suffering from cartilage defects of the medial femoral condyle (average size 4,6cm 2) were included in the study. Cartilage biopsies were taken arthroscopically, the cells were expanded with autologous serum. BioCart™II was implanted after 3 to 6 weeks. The patients were evaluated after 2, 6, 12 weeks, 6 and 12 months. Results: No serious adverse events occurred. 5 patients developed effusion, which resolved in all cases. The blood parameters were normal, there were no allergic reactions or problems of biocompatibility. After 12 months the subjective IKDC was improved postoperatively (p=0.0003; p=0.0001). The objective IKDC was implant hypertrophy in 4 patients, an intact cartilage and bone interface in 7 patients and a small subchondral edema in 4 patients. Conclusions: BioCart™II implantation was tolerated very well in treated patients with no indication for any potential allergic reaction or any impaired biocompatibility. The clinical outcome demonstrated both by MRI and clinical function scoring proved very positive with reduction in pain, improvement in patients' morbidity and good 22.5 Arthroscopic mosaicplasty technique for cartilage knee lesions. Magnetic resonance observation of cartilage repair tissue (MOCART) at a minimum 7 years follow-up.
Osteoarthritis and Cartilage, 2007
This study had the dual aims of establishing a multisite ovine model of articular cartilage injur... more This study had the dual aims of establishing a multisite ovine model of articular cartilage injury repair, whilst also arthroscopy (LSCA) for the postoperative histological assessment of cartilage repair. Methods and Materials: Defects (AE6mm) were created in the trochlea and medial femoral condyle of twenty-one sheep randomised into untreated controls, matrix-induced autologous chondrocyte implantation (MACI[Ò]), or unseeded MACI treatment, then further divided into 8, 10, and 12 week time points. Repair outcomes were examined using LSCA, routine histology, macroscopic ICRS evaluation, magnetic resonance imaging (MRI), and tissue stiffness testing. Interobserver variability and score system correlation was conducted to validate system reliability in assessing cartilage repair. Results: Assessment of MACI treatment by LSCA, MRI, histology, and macroscopic IRCS grading, illustrated improvement in repair compared to controls across all modalities. Additionally, MACI repair resembled native articular cartilage in early-stage remodeling histologically, but the stiffness of the MACI repair was inferior to the native tissue. Interobserver analysis of the blinded LSCA scoring validated our scoring protocol, with almost perfect agreement illustrated (ICC=0.9201). Furthermore, Pearson correlation analysis demonstrated that LSCA scoring correlated (P<0.05) to both MRI and ICRS grading. Conclusions: The assessment of cartilage repair has been primarily limited to macroscopic assessment, variable MRI, or destructive biopsy. The development of non-destructive LSCA cartilage repair assessment will facilitate reliable, high resolution, longterm monitoring of treated lesions in both experimental animal models and clinical patients, by obviating the need for destructive mechanical biopsy.
Treatment of Large Knee Osteochondral Lesions With a Biomimetic Scaffold: Results of a Multicenter Study of 49 Patients at 2-Year Follow-up
The American Journal of Sports Medicine, 2014
Background: Osteochondral knee lesions represent a challenging condition encountered by orthopaed... more Background: Osteochondral knee lesions represent a challenging condition encountered by orthopaedic surgeons. A variety of methods have been developed to repair articular cartilage defects. However, these techniques are limited by donor site morbidity or by the requirement for a staged procedure. Purpose: To assess the effectiveness of a biomimetic osteochondral scaffold for the treatment of large osteochondral knee lesions. Study Design: Case series; Level of evidence, 4. Methods: From 2009 to 2011, a total of 49 patients affected by isolated large osteochondral knee lesions (mean [± SD] size, 4.35 ± 1.26 cm2) were treated with the biomimetic scaffold. Patients were evaluated using the International Knee Documentation Committee (IKDC), Tegner, and visual analog scale (VAS) pain scores, as well as magnetic resonance imaging (MRI) up to 3-year follow-up. The MOCART (magnetic resonance observation of cartilage repair tissue) score was performed to analyze different variables. Biopsies were carried out in 5 patients. Four of the 5 second-look arthroscopies and biopsies were performed on patients with failed results because of ethical issues. Results: The mean IKDC subjective score increased significantly from 45.45 ± 19.29 preoperatively to 70.86 ± 18.08 at 1-year follow-up and to 75.42 ± 19.31 at 2-year follow-up ( P < .001). The IKDC objective score changed from 50% normal and nearly normal knees before treatment to 89.79% at the 2-year follow-up. There was a statistically significant improvement ( P < .005) in VAS score from the preoperative level (6.69 ± 1.88) to the 2-year follow-up (1.96 ± 2.47). Tegner scores increased ( P < .001) from the preoperative value (2.20 ± 0.67) to the 2-year follow-up (4.9 ± 1.73) without achieving preinjury level. A correlation was found between the IKDC subjective score and age ( P < .001, r = −0.497, ρ = −0.502). Patients affected by osteochondritis dissecans (OCD) achieved a statistically significantly better outcome ( P < .05). A subgroup of 19 competitive athletes showed a statistically significantly improvement ( P < .001) in the subjective IKDC (86.5 ± 13.2) compared with the nonathletic subpopulation (69.03 ± 19.41) at the 2-year follow-up. The MRI findings of 30 patients were available at 2-year follow-up: 70% showed complete filling of the lesion, 63.3% had an intact articular surface, and 86% had mild or no effusion. In all cases, in dual T2-weighted fast spin echo sequence, the repair tissue showed a hyperintensive signal with respect to the surrounding subchondral bone; however, no edema was observed. Conclusion: The study findings indicate that the biomimetic scaffold that was investigated is an off-the-shelf, cell-free, and cost-effective implant that can regenerate either cartilage or subchondral bone. The scaffold allows a 1-step surgical procedure that can be used for osteochondral lesions, OCD, and in some cases osteonecrosis.
Arthroscopy Techniques, 2013
The importance of the lateral meniscus in weight bearing, distribution of force, shock absorption... more The importance of the lateral meniscus in weight bearing, distribution of force, shock absorption, articular cartilage protection, proprioception, stabilization of the joint, and joint lubrication is well known. Surgeons currently agree on the importance of preserving the menisci. Different suture techniques have been standardized. These include outsidein, inside-out, and all-inside techniques. The all-inside technique can be used to repair lesions of the posterior horn of the lateral meniscus. However, this technique presents important disadvantages, such as the necessity for an accessory portal and a high risk of neurovascular damage. For these reasons, we have developed a technique in which a suture hook and a shuttle relay are used to pass the suture wire through the meniscal lesion of the posterior horn of the lateral meniscus with an all-inside technique, without the use of accessory portals and cannulas, with a standard 30 arthroscopic camera.
Osteoarthritis and Cartilage, 2007
Purpose: As a one-step arthroscopic procedure, microfracture is frequently considered to be techn... more Purpose: As a one-step arthroscopic procedure, microfracture is frequently considered to be technically easier and associated with less postoperative morbidity than autologous chondrocyte implantation (ACI), which involves both arthrotomy and arthroscopy. Safety was therefore assessed in patients with symptomatic cartilage lesions of the knee treated with either characterized chondrocyte implantation (CCI) using ChondroCelect ® or microfracture. Methods and Materials: CCI (n=57) was compared to microfracture (n=61) in patients with grade III-IV symptomatic cartilage defects of the femoral condyles in a Phase III prospective, multicenter, randomized controlled trial. Safety assessments included adverse events (AEs), physical examination, vital signs, hematology and clinical chemistry. Results: Similar proportions of patients experienced AEs in the CCI (88%) and microfracture (82%) groups; 67% and 59%, respectively,
Tissue Engineering Part A, 2008
Objective: The aim of the study was to investigate the use of a novel hyaluronic acid/polycaprola... more Objective: The aim of the study was to investigate the use of a novel hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Two different surgical implantation techniques in a sheep model were evaluated. Methods: Twenty-four skeletally mature sheep were treated with total medial meniscus replacements, while two meniscectomies served as empty controls. The animals were divided into two groups: cell-free scaffold and scaffold seeded with autologous chondrocytes. Two different surgical techniques were compared: in 12 animals, the implant was sutured to the capsule and to the meniscal ligament; in the other 12 animals, also a transtibial fixation of the horns was used. The animals were euthanized after 4 months. The specimens were assessed by gross inspection and histology. Results: All implants showed excellent capsular ingrowth at the periphery. Macroscopically, no difference was observed between cell-seeded and cell-free groups. Better implant appearance and integrity was observed in the group without transosseous horns fixation. Using the latter implantation technique, lower joint degeneration was observed in the cell-seeded group with respect to cell-free implants. The histological analysis indicated cellular infiltration and vascularization throughout the implanted constructs. Cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs. Conclusion: The current study supports the potential of a novel HYAFF/polycaprolactone scaffold for total meniscal substitution. Seeding of the scaffolds with autologous chondrocytes provides some benefit in the extent of fibrocartilaginous tissue repair.
Sports Medicine and Arthroscopy Review, 2008
In recent years, regenerative techniques, such as autologous chondrocyte implantation (ACI), have... more In recent years, regenerative techniques, such as autologous chondrocyte implantation (ACI), have emerged as a potential therapeutic option for the treatment of chondral lesions. However, the good results reported have to be weighed against the number of problems that can be observed with traditional ACI methods. To address these problems, the socalled second generation ACI techniques have been developed. Autologous chondrocyte transplantation on a 3-dimensional matrix was introduced in clinical practice from 1998 to 1999 and results at short to medium-term follow-up are well documented for different types of scaffolds. These techniques may be used for the treatment of large chondral lesions in the young, active population and highly competitive athletes, but long-term and randomized controlled studies will be needed to confirm reliability of these procedures.
Osteoarthritis and Cartilage, 2008
Osteoarthritis and Cartilage, 2007
Purpose: Evaluation of the occurrence and morphology of meniscus regrowth after complete medial r... more Purpose: Evaluation of the occurrence and morphology of meniscus regrowth after complete medial removal of the meniscus and its effect on the hyaline articular cartilage Methods and Materials: 32 NZW rabbits were used according to a protocol permitted by both, the Institutional and the Governmental Ethics Committee. All animals were male and skeletally mature as checked by standard x-ray. An open medial parapatellar approach was performed under sterile conditions. The medial meniscus was completely excised from the synovial junction. Particular care was taken at the posterior horn for complete separation from all 12 weeks. Macroscopic grading was performed in accordance with
Osteoarthritis and Cartilage, 2007
Autologous Chondrocyte Implantation (ACI) proposed by Brittberg in 1994 [1], involving re-implant... more Autologous Chondrocyte Implantation (ACI) proposed by Brittberg in 1994 [1], involving re-implantation of autologous cells that have been isolated from cartilage harvested from the patient and expanded in repair of focal articular cartilage lesions. A second-generation tissueengineering approach to cartilage repair was proposed, which uses a biodegradable three-dimensional scaffold for cell proliferation. This scaffold is entirely based on the benzylic ester of hyaluronic acid (HYAFF ® 11, Fidia Advanced Biopolymers Laboratories, Padova,
Osteoarthritis and Cartilage, 2007
Purpose: There is an increase in IL-1ß following joint injury which up-regulates catabolic enzyme... more Purpose: There is an increase in IL-1ß following joint injury which up-regulates catabolic enzymes breaking down the cartilage matrix. Little is known about the added effect of joint motion on matrix degradation. In this in vitro study we investigated proteoglycan/ GAG-release, an indicator for matrix breakdown , using a joint simulator applying dynamic loads and articular motion onto living cartilage explants in the presence of IL-1ß. Methods and Materials: were obtained from a local abattoir within 24 hours of slaughter. Nine cartilage disks were removed from the trochlea using a 14mm punch. After a 5 day pre-culture, 3 disks were tested in a joint simulator in controls. All tests were performed in serum-free, DMEM:F12 media for 3 hours. Medium was then individually collected and analyzed for the presence of proteoglycans/GAGs using the DMMB assay. Results: Cartilage explants cultured in the presence of IL-1ß (no release when compared to control. When motion was applied release when compared to control and a 2.6-fold increase when Conclusions: The combination of joint articulation and IL-1 ß resulted in the highest amount of proteoglycan/GAG release into the media. This preliminary evidence suggests that joint articulation following joint injury may be detrimental to the cartilage matrix.
Journal of Tissue Engineering and Regenerative Medicine, 2010
The present in vivo preliminary experiment is aimed at testing mechanical and biological behaviou... more The present in vivo preliminary experiment is aimed at testing mechanical and biological behaviour of a new nano-structured composite multilayer biomimetic scaffold for the treatment of chondral and osteochondral defects. The three-dimensional biomimetic scaffold (Fin-Ceramica Faenza S.p.A., Faenza-Italy) was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles, in two configurations, bi-and tri-layered, to reproduce, respectively, chondral and osteochondral anatomy. Chondral defects (lateral condyle) and deep osteochondral defects (medial condyle) were made in the distal epiphysis of the third metacarpal bone of both forelimbs of two adult horses and treated respectively with the chondral and osteochondral grafts. Both animals were euthanised six months follow up. The images obtained at the second look arthroscopy evaluation, performed two months after surgery, demonstrated good filling of the chondral and osteo-chondral defects without any inflammatory reaction around and inside the lesions. At the histological analysis the growth of trabecular bone in the osteochondral lesion was evident. Only in one case, the whole thickness of the osteochondral lesion was filled by fibrocartilaginous tissue. The formation of a tidemark line was evident at the interface with the newly formed bone. Newly formed fibrocartilaginous tissue was present in the area of the chondral defect. Initial alignment of the collagen fibres was recognisable with polarised light in both groups. The results of the present pilot study showed that this novel osteochondral and chondral scaffold may act as a suitable matrix to facilitate orderly regeneration of bone and hyaline-like cartilage.
Erratum: Novel nanostructured scaffold for osteochondral regeneration: pilot study in horses
Journal of Tissue Engineering and Regenerative Medicine, 2012
Journal of Orthopaedic Research, 2009
The objective of this article was to investigate the safety and regenerative potential of a newly... more The objective of this article was to investigate the safety and regenerative potential of a newly developed biomimetic scaffold when applied to osteochondral defects in an animal model. A new multilayer gradient nano-composite scaffold was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. In the femoral condyles of 12 sheep, 24 osteochondral lesions were created. Animals were randomized into three treatment groups: scaffold alone, scaffold colonized in vitro with autologous chondrocytes and empty defects. Six months after surgery, the animals were sacrificed and the lesions were histologically evaluated. Histologic and gross evaluation of specimens showed good integration of the chondral surface in all groups except for the control group. Significantly better bone regeneration was observed both in the group receiving the scaffold alone and in the group with scaffold loaded with autologous chondrocytes. No difference in cartilage surface reconstruction and osteochondral defect filling was noted between cell-seeded and cell-free groups. In the control group, no bone or cartilage defect healing occurred, and the defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed. The results of the present study showed that this novel osteochondral scaffold is safe and easy to use, and may represent a suitable matrix to direct and coordinate the process of bone and hyaline-like cartilage regeneration. The comparable regeneration process observed with or without autologous chondrocytes suggests that the main mode of action of the scaffold is based on the recruitment of local cells.