Autologous Chondrocyte Implantation With Knee Osteotomy in Middle-Aged Patients Demonstrates a Chondrogenic Transcriptomic Profile and Favorable Histological Repair

Objective The primary aim was to characterize cartilage repair following autologous chondrocyte implantation (ACI) with knee osteotomy in middle-aged patients, hypothesizing favorable histological repair and a chondrogenic transcriptomic profile. Secondary comparisons with isolated osteotomy were exploratory. Design This prospective case series with a nonrandomized comparison group included 12 patients aged 50–65 years with International Cartilage Repair Society (ICRS) grade 3–4 cartilage defects (>4 cm 2 ) and varus malalignment. Six underwent two-stage ACI with osteotomy and six underwent osteotomy alone; allocation followed Japanese insurance indications for ACI. Patient-reported outcomes were assessed preoperatively and at 1 year. Both groups underwent second-look arthroscopy, ICRS II histological assessment, and RNA sequencing. Graft biochemical properties were compared between younger and older cohorts. Results The ACI group had higher macroscopic repair scores (10.3 ± 1.0 versus 6.0 ± 4.4; P = 0.04) and histological scores (median, 75 versus 50; P = 0.03). Lysholm scores improved in both groups (both P = 0.031); KOOS, IKDC, and VAS changes were not significant. No between-group differences in changes from baseline were significant for any patient-reported outcome. COL2A1, ACAN, and COMP expression was higher in the ACI group. Graft sGAG content and cell number did not differ significantly between age groups. Conclusion ACI with osteotomy showed favorable histological repair and a chondrogenic transcriptomic profile. The small sample, nonrandomized allocation, and short follow-up make between-group findings exploratory. Larger, longer-term studies are needed to establish clinical significance and durability.