Transplantation Of Tissue-engineered Cartilage Research Articles

Controlling the Phenotype of Macrophages Promotes Maturation of Tissue-Engineered Cartilage.

Tissue reactions after transplantation can affect the maturation and prognosis of the transplanted engineered tissue in regenerative medicine. Since macrophages are broadly subdivided into two major phenotypes, inflammatory (M1) and anti-inflammatory/wound healing (M2), in this study, we examined the properties of macrophages in transplantation of tissue-engineered cartilage, to clarify their effects on cartilage maturation. Human chondrocytes were embedded in a poly-L-lactic acid scaffold, which was transplanted subcutaneously on the back in athymic mice. When the constructs were analyzed by real-time polymerase chain reaction, interleukin 1 expression was detectable at 4 days, and it reached a peak at 7 days. Interleukin 6 expression was increased at 7 to 11 days, suggesting that M1 macrophages were abundant around this time. On the other hand, expression of markers for M2 macrophages occurred rather later, with Fizz and Ym1 expression peaking at around 11 to 14 days, possibly indicating that polarization of macrophages in tissue-engineered cartilage could shift from M1 to M2 around 11 days after transplantation. When cultured by using the conditioned medium of M2 macrophages, chondrocytes showed significantly increased expression of type 2 collagen, suggesting that M2 macrophages could enhance the maturation of tissue-engineered cartilage. Also, by partially depleting macrophages with clodronate liposomes in the initial period, during which M1 macrophages were dominant, more cartilage matrix accumulated in transplanted constructs at 2 weeks. It was suggested that polarization of macrophages shifted from M1 to M2 in the transplantation of tissue-engineered cartilage, and controlling the polarization could be advantageous for the maturation of transplanted engineered tissues. Impact statement In transplantation of engineered tissues, it is imperative for immune reactions to proceed in a proper and timely manner. In this study, we transplanted tissue-engineered cartilage consisting of a biodegradable polymer scaffold and chondrocytes, and examined the properties of macrophages. It was shown that the polarization of macrophages shifted from inflammatory (M1) to anti-inflammatory/wound healing (M2) around 11 days after transplantation. Partial suppression of macrophages at the early stage of transplantation, which were mainly M1 macrophages, promoted more accumulation of cartilage matrix. This study indicates a possible approach to facilitate cartilage maturation by intervening in the polarity of macrophages.

Transplantation of Tissue-Engineered Cartilage in an Animal Model (Xenograft and Autograft): Construct Validation.

Tissue engineering holds great promise for cartilage repair with minimal donor-site morbidity. The in vivo maturation of a tissue-engineered construct can be tested in the subcutaneous tissues of the same species for autografts or of immunocompromised animals for allografts or xenografts. This section describes detailed protocols for the surgical transplantation of a tissue-engineered construct into an animal model to assess construct validity.

Early Stage Foreign Body Reaction against Biodegradable Polymer Scaffolds Affects Tissue Regeneration during the Autologous Transplantation of Tissue-Engineered Cartilage in the Canine Model

To overcome the weak points of the present cartilage regenerative medicine, we applied a porous scaffold for the production of tissue-engineered cartilage with a greater firmness and a 3D structure. We combined the porous scaffolds with atelocollagen to retain the cells within the porous body. We conducted canine autologous chondrocyte transplants using biodegradable poly-L-lactic acid (PLLA) or poly-DL-lactic-co-glycolic acid (PLGA) polymer scaffolds, and morphologically and biochemically evaluated the time course changes of the transplants. The histological findings showed that the tissue-engineered constructs using PLLA contained abundant cartilage 1, 2, and 6 months after transplantation. However, the PLGA constructs did not possess cartilage and could not maintain their shapes. Biochemical measurement of the proteoglycan and type II collagen also supported the superiority of PLLA. The biodegradation of PLGA progressed much faster than that of PLLA, and the PLGA had almost disappeared by 2 months. The degraded products of PLGA may evoke a more severe tissue reaction at this early stage of transplantation than PLLA. The PLLA scaffolds were suitable for cartilage tissue engineering under immunocompetent conditions, because of the retarded degradation properties and the decrease in the severe tissue reactions during the early stage of transplantation.

Transplantation of Tissue-engineered Cartilage for Repair of Osteochondral Defects in the Knee (SS-27)

The use of chondral progenitor cells is an innovative therapeutic option for treatment of osteochondral lesions of the knee and this study was conducted to evaluate the clinical outcome at medium-term follow-up. Arthroscopic repair of osteochondral lesion of the knee by autologous highly committed chondrogenic precursors (Co.don AG, Teltow, Germany) was performed in twenty-three patients, 18 men and 5 women with a mean age of 29.2 ± 10.4 years. Fifteen lesions were located on medial femoral condyle, six on lateral and two on femoral throclea. The average size was 3.4 ± 1.0 cm(2). All patients were evaluated preoperatively and postoperatively using VAS score, Lysholm knee score and International Knee Documentation Committee(IKDC). Magnetic resonance imaging (MRI) examinations were performed at 12 and 24 months after surgery. Three patients had second-look arthroscopies and biopsies. No early or late complications related to arthroscopic procedure were reported. Median follow-up time was 39 months(36-41). Clinical evaluation showed significant improvement in the Lysholm score (from 54.8 to 82.5), IKDC (from 48.5 to 72.5) (P≤.001). The average VAS score decreased from a preoperative value of 5.6(SD:2.5) to 1.8(SD:2.0). The postoperative MRI examinations showed complete defect filling in 22 of 23 treated patients. The second-look arthroscopies and biopsies were done 18.5 ± 5.4 months after transplantation. All the second-look arthroscopies confirmed good integration of repair tissue to the adjacent cartilage and complete defect filling. Biopsies were categorized as hyaline cartilage in all cases. arthroscopic transplantation of autologous highly committed chondrogenic precursors is an effective and safe method of treating symptomatic osteochondral defects of the knee. The reported medium-term outcomes are encouraging, however, further study with longer follow-up are necessary to determine the inner endurance of reparative tissue and its structural integrity over time.

Results of Transplantation of Tissue-Engineered Cartilage for the Treatment of Cartilage Defects in the Knee Joint

Results of Transplantation of Tissue-Engineered Cartilage for the Treatment of Cartilage Defects in the Knee Joint

Transplantation of tissue-engineered cartilage for the treatment of osteochondritis dissecans in the elbow: Outcomes over a four-year follow-up in two patients

The ideal goal of treatment for osteochondral lesions is to resurface the lesions with hyaline cartilage and to prevent the occurrence of secondary osteoarthritis. To achieve this goal, autologous chondrocyte implantations (ACI) have been developed and clinically applied to osteochondral lesions of the knee and ankle joints.2,3,7,20,25,26,33 Osteochondral lesions such as osteochondral dissecans (OCD) or osteochondral fractures are frequently involved in the elbow. Although the implementation of ACI in the elbow has been reported,17,28 postoperative follow-up is limited.

Osteochondritis dissecans involving the trochlea of the humerus treated with transplantation of tissue-engineered cartilage: A case report

Osteochondritis dissecans (OCD) of the elbow is typically located in the capitellum of the humerus in young teenagers. There are only a few reports of OCD in the trochlea of the humerus.9,17,28 The ideal goal of treatment for OCD lesions is to resurface the osteochondral defect with hyaline cartilage and to prevent the occurrence of osteoarthritis. Recently, to achieve this surgical goal, autologous chondrocyte implantations (ACIs) or tissue-engineered cartilage transplantations (TCTs) have been performed for OCD lesions of the knee and the ankle.

The long-term results of meniscus transplantation for articular cartilage defects in the knee joint

The purpose of this study was to examine the long-term clinical results of meniscus transplantation for articular cartilage defects in the knee joint. The type of study was case series. From October 1990 to June 1995, eight cases underwent allogenic or autogenic meniscus transplantations for articular cartilage defects, and seven cases were available for follow-up evaluations. The age at surgery ranged from 14 to 42 years of age (average 22.5). In one case, transplantation of tissue-engineered cartilage was performed due to pain 5 years after surgery. The other six cases were followed up for 8-13 years (average 10.1). The size of the cartilage defect ranged from 1.0 to 6.3 cm2 (average 2.8 cm2). Patients were evaluated with the Lysholm score and MR images. We also performed arthroscopic examinations in three cases at the final evaluation. This study leads to the conclusion that meniscus transplantation for articular cartilage damage is not comparable to autologous chondrocyte transplantation. Two cases showed a good clinical outcome but the tissue remained as fibrocartilage tissue in the long-term.

Lateral Compartment Osteoarthritis of the Knee After Meniscectomy Treated by the Transplantation of Tissue-Engineered Cartilage and Osteochondral Plug

Management of osteoarthritis of the knee after meniscectomy has been challenging, especially for young patients, because articular cartilage has very poor healing capacity because of its lack of vessels, nerve supply, and isolation from systemic regulation. Osteoarthritic lesions often involve both femoral and tibial cartilage, requiring treatments for both lesions. We report the case of a 14-year-old girl with lateral compartment osteoarthritis of the knee after a total meniscectomy of the discoid meniscus, who was successfully treated by the transplantation of both tissue-engineered cartilage made ex vivo for a femoral lesion and an autologous osteochondral plug for a tibial lesion. We treated both femoral and tibial cartilage defects simultaneously with this procedure. We confirmed cartilaginous regeneration in both femoral and tibial lesions at second-look arthroscopy. This procedure is one option to prevent further development of osteoarthritis in young patients.

Osteochondritis dissecans of the talus treated by the transplantation of tissue-engineered cartilage

Management of osteochondral lesions of the joint has been difficult, because articular cartilage has a poor healing capacity as a result of its lack of vessels, nerve supply, and its isolation of systemic regulation. Although a lot of basic research and surgical treatments for cartilage repair have focused on osteochondral lesions in the knee joint, orthopedic surgeons have recently diverted their attention to osteochondral lesions in the ankle joint, partly because of the widespread introduction of arthroscopy in ankle surgery. There have been many attempts to treat articular cartilage defects in the ankle joint as well as in the knee joint. However, no treatment has achieved efficient healing with hyaline cartilage. Recently, tissue engineering technique for cartilage repair has been gaining much attention in the orthopedic field. In this study, we reported on a patient with osteochondritis dissecans of the talar dome, successfully treated by transplantation of tissue-engineered cartilage made ex vivo using atelocollagen gel and low tibial osteotomy.

Transplantation of tissue-engineered cartilage for excessive osteochondritis dissecans of the elbow

Controversy surrounds the treatment of osteochondritis dissecans (OCD) of the elbow. Until now, OCD has been treated by arthrotomy with debridement, drilling of subchondral bone, 15 Menche D.S. Vangsness Jr, C.T. Pitman M. Gross A.E. Peterson L. The treatment of isolated articular cartilage lesion in young individual. Instr Course Lect. 1998; 47: 505-505 PubMed Google Scholar , 22 Peterson R.K. Savoie F.H. Field L.D. Osteochondritis dissecans of the elbow. Instr Course Lect. 1999; 48: 393-398 PubMed Google Scholar and surgical reattachment of the fragment. 3 Bradley JP. Elbow injuries in children and adolescents. In: Pediatric and adolescent sports medicine. Philadelphia: Saunders; 1994. p. 242-61 Google Scholar , 9 Indelicato P.A. Jobe F.W. Kerlan R.K. et al. Correctable elbow lesions in professional baseball players a review of 25 cases. Am J Sports Med. 1979; 7: 72-75 Crossref PubMed Scopus (57) Google Scholar , 10 Jackson D.W. Silvino N. Reiman P. Osteochondritis in the female gymnast's elbow. Arthroscopy. 1989; 5: 129-136 Abstract Full Text PDF PubMed Scopus (123) Google Scholar , 11 Katsube K. Ochi M. Uchio Y. et al. Repair of articular cartilage defects with cultured chondrocytes in Atelocollagen gel. Comparison with cultured chondrocytes in suspension. Arch Orthop Trauma Surg. 2000; 120: 121-127 Crossref PubMed Scopus (9) Google Scholar , 12 Kuwahara Y. Inoue G. Osteochondritis dissecans of the elbow managed by Herbert screw fixation. Orthopedics. 1998; 21: 449-451 PubMed Google Scholar In cases in which there are excessively detached fragments of the OCD without a bony segment, however, no previous reports have demonstrated an advantage to fragment fixation or replacement. 2 Bauer M. Jonsson K. Josefsson P.O. Linden B. Osteochondritis dissecans of the elbow a long-term follow-up study. Clin Orthop. 1992; 284: 156-160 PubMed Google Scholar , 14 McManama Jr, G.B. Micheli L.J. Berry M.V. Sohn R.S. The surgical treatment of osteochondritis of the capitellum. Am J Sports Med. 1985; 13: 11-21 Crossref PubMed Scopus (91) Google Scholar , 24 Singer K.M. Roy S.P. Osteochondrosis of the humeral capitellum. Am J Sports Med. 1984; 12: 351-360 Crossref PubMed Scopus (104) Google Scholar

Clinical Results of Transplantation of Tissue-Engineered Cartilage and Future Direction of Cartilage Repair - Novel Approach with Minimally Invasive Procedure -

Clinical Results of Transplantation of Tissue-Engineered Cartilage and Future Direction of Cartilage Repair - Novel Approach with Minimally Invasive Procedure -

Articular cartilage repair using tissue engineering technique--novel approach with minimally invasive procedure.

Articular cartilage has very limited potential to spontaneously heal, because it lacks vessels and is isolated from systemic regulation. Although there have been many attempts to treat articular cartilage defects, such as drilling, microfracture techniques, soft tissue grafts or osteochondral grafts, no treatment has managed to repair the defects with long-lasting hyaline cartilage. Recently, a regenerative medicine using a tissue engineering technique for cartilage repair has been given much attention in the orthopedic field. In 1994, Brittberg et al. introduced a new cell technology in which chondrocytes expanded in monolayer culture were transplanted into the cartilage defect of the knee. As a second generation of chondrocyte transplantation, since 1996 we have been performing transplantation of tissue-engineered cartilage made ex vivo for the treatment of osteochondral defects of the joints. This signifies a concept shift from cell transplantation to tissue transplantation made ex vivo using tissue engineering techniques. We have reported good clinical results with this surgical treatment. However, extensive basic research is vital to achieve better clinical results with this tissue engineering technique. This article describes our recent research using a minimally invasive tissue engineering technique to promote cartilage regeneration.