Biocompatible bacterial nanocellulose (BNC) shows high potential as wound dressing and dura mater replacement, and even for the development of blood vessel or cartilage implants. Thus, the regenerative capacity of BNC implants was analyzed using a standardized bovine cartilage punch model. Cartilage rings with an outer diameter of 6 mm and an inner defect diameter of 2 mm were derived from the trochlear groove (femur-patellar articulation site). BNC implants were cultured inside the cartilage rings for up to 12 weeks. Cartilage-BNC-constructs were then evaluated by histology (hematoxylin/eosin; safranin O), immunohistology (aggrecan, collagens 1 and 2), and for protein content, mRNA expression, and push-out force of the implants. Cartilage-BNC-constructs displayed vital chondrocytes (≥ 90% until week 9; > 80% until 12 weeks), preserved matrix integrity during culture, limited loss of matrix-bound proteoglycan from ‘host’ cartilage or cartilage-BNC-interface, and constant release of proteoglycans into the culture supernatant. In addition, the content of the matrix protein collagen 2 in cartilage and cartilage-BNC-interface was approximately constant over time (with very limited quantities of collagen 1). Interestingly, BNC implants showed: (1) cell colonization of the implant; (2) progressively increasing mRNA levels for the proteoglycan aggrecan and collagen 2 (max. fivefold); and (3) significantly increasing push-out forces during culture (max. 1.6-fold). Retained tissue integrity and progressively increasing chondrogenic differentiation in implant and cartilage-implant-interface suggest beginning cartilage regeneration in the BNC in the present model and indicate a high potential of BNC as a cartilage replacement material. Thus, the present model appears suitable to predict the in vivo performance of cartilage replacement materials (e.g., BNC) for tissue engineering.