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

Abstract

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.

Regenerative Cartilage made by Fusion of Cartilage Elements derived from Chondrocyte Sheets prepared in Temperature-Responsive Culture Dishes

“…Although the use of biodegradable polymers that show low speed of biodegradation could reduce the foreignbody reactions under the in vivo conditions 8) , it is hard to eliminate this adverse reaction, as far as we use any biodegradable polymers as scaffolds. Thus, an effective method to regenerate threedimensional tissues and also to minimize foreign-body reactions after transplantation should be established.…”

“…However, most biodegradable polymers are biologically absorbed by macrophages, causing foreign-body reactions 6,7) . Although we chose the PLLA scaffold in the medical introduction as those tissue reactions were relatively low, especially at the early stage of transplantation 8) , those tissue reactions were somewhat inevitable even in the PLLA scaffold.…”

Evaluation of <i>in vivo</i> migration of chondrocytes from tissue-engineered cartilage that was subcutaneously transplanted in mouse model

“…In our previous study, the tissue-engineered cartilage matured 8 weeks after transplantation [6]. At 8 weeks, the transplanted chondrocytes were completely embedded within cartilaginous matrices, which implied that migration of chondrocytes from the transplants to other organs hardly occurred after that time.…”

Relation between speed of sound measured by using ultrasound and magnetic resonance images and elasticity in tissue-engineered cartilage

“…To make tissueengineered cartilage, the atelocollagen aliquot containing the chondrocytes was applied to PLLA scaffolds with a size of 50 x 6 x 3 mm, and kept in an incubator for 3 hr for gelation [1][2]. Regarding the transplantation procedure, 10-week-old male F344/NJcl-rnu/rnu rats (Nisseizai, Tokyo, Japan) were anesthetized by intraperitoneal injection of sodium pentobarbital (50 mg/kg).…”