Autologous Culture Expanded Iliac Crest Chondrocytes in Chitosan Hyaluronic Acid Dialdehyde Gel Regenerate Caprine Growth Plate

• Published in: Regenerative engineering and translational medicine 2023-09, Vol.9 (3), p.397-406
• Main Authors: Madhuri, Vrisha, Ramesh, Sowmya, Rajagopal, Karthikeyan, Chilbule, Sanjay K., Nair, Prabha. D., Walter, Noel Malcolm
• Format: Article
• Language: English
• Subjects: Biomaterials; Biomedical Engineering and Bioengineering; Bones; Cartilage; Chemistry and Materials Science; Chitosan; Defects; Feasibility studies; Fluorescence; Goats; Histology; Hyaluronic acid; Hydrogels; In Honor of Robert Langer's 70th Birthday – Vol. 2; Limbs; Materials Science; Original Research; Regenerative Medicine/Tissue Engineering; Transplantation
• ISSN: 2364-4133; 2364-4141
• DOI: 10.1007/s40883-022-00289-4

Purpose Allogenic and autologous chondrocytes have been used to reconstitute damaged growth plates in small and large animals with variable success. We evaluated the efficacy of growth plate chondrocytes in a chitosan-hyaluronic acid dialdehyde (CHDA) hydrogel in repairing damaged growth plates using an immature goat model ( n  = 4). Methods Chondrocytes were harvested from the ipsilateral iliac crest cartilage and expanded in vitro. The culture-expanded cells were seeded in a CHDA hydrogel prior to transplantation. A physeal defect measuring approximately 1 cm 3 was created in the proximal medial tibial physis, and cell-seeded hydrogel was transplanted into the defect. One animal that received green fluorescent protein-labeled cells (to determine the fate of transplanted cells) was sacrificed at 2 months, while the others were sacrificed at 6 months. The outcome was assessed by histology and radiographs. Results Our results indicated the presence of transplanted cells in the short term. The histology of the transplanted growth plate was comparable to normal and demonstrated a columnar arrangement with endochondral ossification. The mean tibial length of the transplanted limb was 18.63 (16.5 to 20.3), while that of the contralateral limb was 18.58 (16.5 to 20.4). Mean tibial valgus at the transplanted and contralateral sides were 6.56° (5.2 to 8.9) and 4.63° (1.4 to 7.4), respectively, and significantly different when compared to the defect alone, which had a varus deformity of 2.9° (0.2 to 5.6). Conclusion This study demonstrates the feasibility of encapsulating autologous chondrocytes in a novel hydrogel for growth plate regeneration, thereby preventing bony bridge formation and varus deformity. Layman Summary In children, growth plate cartilage is responsible for the growth of long bones. The structure is fragile, such that any injury or infection can interfere with normal growth, leading to inferior quality bone quality. If not treated early, it often leads to permanent disability; multiple corrective surgeries and time-consuming lengthening procedures are required to correct the deformity. In this study, using a young goat model, we tested if transplanting autologous growth plate cells at the defect site can restore normal bone growth, eliminating the need for laborious surgical procedures. Our results showed that it is likely to establish normal growth of the bone without bone abnormality using this technique.