Nose2Knee Technology

How can the nose help your knee – learn more about the science behind N-TEC and the generation of your personalized graft.

Cell-based therapies using cartilage cells (i.e., chondrocytes) from a healthy area of the knee joint are already available as routine treatments but exhibit several drawbacks.

Innovations in Nose2Knee

The engineered nasal cartilage graft (N-TEC) combines two innovations to overcome the current drawbacks:

  • Use of cartilage cells from the nose

Harvesting cartilage from the nose is associated with minimal donor-site-morbidity (no adverse reactions in over 100 patients) and avoids damage to a still healthy area of the knee. In addition, research studies have proven that nasal chondrocytes have a better capacity to expand and form cartilage of superior quality than chondrocytes from the knee joint. The resulting cartilage graft can stand mechanical forces typically associated with the joint loading and the cells react in the same way as knee chondrocytes by producing proteins necessary for joint lubrication.

Nasal cartilage biopsy.
(Universität Basel, photo by Christian Flierl)
  • Implantation of a tissue instead of a cell-based graft

The implantation of an engineered cartilage tissue provides more stability to the graft and more protection of the cells from inflammatory insults.

Therefore, one key advance of the program is the implantation of NC-based tissue-engineered cartilage (N-TEC) in OA joints, which is expected to regenerate the cartilage layer, dampen synovial inflammation, restore joint functionality, and thus ultimately improve the patient’s quality of life.

Engineered cartilage graft of about 20cm2, manufactured from a nasal cartilage biopsy and ready for implantation.
(Universität Basel, photo by Christian Flierl)

Clinical studies so far

Several clinical studies for the treatment of articular cartilage defects have been carried out with the Nasal chondrocyte Tissue Engineered Cartilage (N-TEC).

Initial studies have shown the safety and efficacy of using Nasal chondrocyte Tissue Engineered Cartilage (N-TEC) to heal focal cartilage defects in the knee, alleviate patient’s symptoms, and thus improve quality of life.

A phase I study (clinicaltrials.gov identifier: NCT01605201) has been carried out with N-TEC on focal full-cartilage trochlea or femoral condyle lesions of a size of 2-8 cm2. Overall, 18 patients have been included in this study. Study results showed the safety of the implanted graft, indicating a clinical benefit for the patient and a resurfacing of the joint area with the implanted cartilage. No serious adverse reactions have been reported over the planned follow-up period of 2 years and most patients could profit from the treatment. Based on these promising results, an international multicenter phase II clinical study has been initiated.

A phase II (clinicaltrials.gov identifier: NCT02673905) international multicenter study, EU-funded project BIO-CHIP, has been carried out in four European countries in five clinical centers (University Hospital Basel, Switzerland (lead); University Hospital Sveti Duh, Croatia; Medical Centre – University of Freiburg, Germany; Orthopaedic Hospital König Ludwig Haus, Germany; Galeazzi Orthopaedic Institute, Italy). 108 Patients have been enrolled and 97 were treated with the nasal chondrocyte tissue engineered cartilage (N-TEC) or the cell-seeded scaffold (N-CAM). The study was closed in November 2022. Results showed that patients of both groups could benefit from the therapy, but with statistically significant superiority of outcome (globally and related to symptoms, sports activities, and quality of life) in the patient group treated with mature engineered cartilage (N-TEC).

Besides PFOA, this treatment can in the future be extended to other forms of OA (medial, lateral, tricompartimental) in the knee/other joints, maximizing the impacts generated by the project and expanding the patient populations that can benefit from it.

Recent publications

  • Mumme, M., Barbero, A., Miot, S., Wixmerten, A., Feliciano, S., Wolf, F., Asnaghi, A. M., Baumhoer, D., Bieri, O., Kretzschmar, M., Pagenstert, G., Haug, M., Schaefer, D. J., Martin, I., & Jakob, M. (2016). Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial. Lancet (London, England), 388(10055), 1985–1994. https://doi.org/10.1016/S0140-6736(16)31658-0
  • Pelttari, K., Pippenger, B., Mumme, M., Feliciano, S., Scotti, C., Mainil-Varlet, P., Procino, A., von Rechenberg, B., Schwamborn, T., Jakob, M., Cillo, C., Barbero, A., & Martin, I. (2014). Adult human neural crest-derived cells for articular cartilage repair. Science translational medicine, 6(251), 251ra119. https://doi.org/10.1126/scitranslmed.3009688
  • Fulco, I., Miot, S., Haug, M. D., Barbero, A., Wixmerten, A., Feliciano, S., Wolf, F., Jundt, G., Marsano, A., Farhadi, J., Heberer, M., Jakob, M., Schaefer, D. J., & Martin, I. (2014). Engineered autologous cartilage tissue for nasal reconstruction after tumor resection: an observational first-in-human trial. Lancet (London, England), 384(9940), 337–346. https://doi.org/10.1016/S0140-6736(14)60544-4
  • Mumme, M., Steinitz, A., Nuss, K. M., Klein, K., Feliciano, S., Kronen, P., Jakob, M., von Rechenberg, B., Martin, I., Barbero, A., & Pelttari, K. (2016). Regenerative Potential of Tissue-Engineered Nasal Chondrocytes in Goat Articular Cartilage Defects. Tissue engineering. Part A, 22(21-22), 1286–1295. https://doi.org/10.1089/ten.TEA.2016.0159
  • Wixmerten, A., Miot, S., Bittorf, P., Wolf, F., Feliciano, S., Hackenberg, S., Häusner, S., Krenger, W., Haug, M., Martin, I., Pullig, O., & Barbero, A. (2023). Good Manufacturing Practice-compliant change of raw material in the manufacturing process of a clinically used advanced therapy medicinal product-a comparability study. Cytotherapy, 25(5), 548–558. https://doi.org/10.1016/j.jcyt.2023.01.003
  • Acevedo Rua, L., Mumme, M., Manferdini, C., Darwiche, S., Khalil, A., Hilpert, M., Buchner, D. A., Lisignoli, G., Occhetta, P., von Rechenberg, B., Haug, M., Schaefer, D. J., Jakob, M., Caplan, A., Martin, I., Barbero, A., & Pelttari, K. (2021). Engineered nasal cartilage for the repair of osteoarthritic knee cartilage defects. Science translational medicine, 13(609), eaaz4499. https://doi.org/10.1126/scitranslmed.aaz4499

How is the Nose2Knee procedure performed?

Nose2Knee procedure has 3 distinct steps:

  1. Nasal cartilage biopsy
  2. Cartilage manufacturing
  3. Cartilage graft implantation
Diagram of the graft production in the ENCANTO project.

Nasal cartilage biopsy

It is performed by an Ear-Nose-Throat/Plastic surgeon. A small biopsy (6 mm in diameter) of nasal cartilage is harvested from the nasal septum of the patient under local anesthesia (visit 1) and shipped to the manufacturing sites as starting material for graft manufacturing.

Punching of the biopsy to have a defined size (6 mm diameter) as starting material for graft production.
(Universität Basel, photo by Christian Flierl)

Manufacturing process

The tissue is transported to a specialized, good manufacturing practice (GMP) facility and treated with an enzyme that extracts cells from the extracellular matrix. The isolated chondrocytes are multiplied in a nutrient solution for two weeks and then loaded into a collagen scaffold and cultured for an additional two weeks with a new solution allowing them to grow and build up a cartilage-like tissue. After a total of 4 weeks, the cartilage graft is shaped to fit the cartilage defect to be repaired.

The cells are grown in an incubator.
(Universität Basel, photo by Christian Flierl)
Quality control is of utmost importance and all the grown cells are carefully counted.
(Universität Basel, photo by Christian Flierl)

All cell culture steps are performed in a highly controlled and sterile laboratory called a clean room by trained and qualified personnel according to national and international regulations for Advanced Therapy Medicinal Products

Cell culture process in a sterile laboratory in a biosafety workbench.
(Universität Basel, photo by Christian Flierl)

Cartilage graft implantation

After four weeks of manufacturing, the graft is shipped to the clinical site where the engineered tissue will be implanted via arthrotomy (visit 2). The degenerated cartilage of the patellofemoral joint will be debrided and osteophytes removed before implantation. Corrections of anatomic abnormalities and patella-stabilizing procedures will be performed if necessary.

Implantation of the engineered cartilage graft into the knee defect.
(University Hospital Sveti Duh Zagreb, Photo by Alan Ivković)

What after?

After surgical intervention, all patients will be subjected to physiotherapy, as this can have a significant impact on the outcome. For rehabilitation, guidance via an internet platform called will be used. Compliance and progress of the patients will be digitally monitored. The follow-up will continue for two years to assess the clinical efficacy of the treatment.