Safety and Efficacy Study of HYTOP® in the Treatment of Focal Chondral Defects.

Safety and Efficacy of a Novel, Cell-free Cartilage Repair Construct in the Treatment of Focal Chondral Defects Involving the Femoro-tibial Compartment of the Knee Joint.

The two-layer bioresorbable HYTOP® matrix consists of an upper layer of highly purified porcine splint-skin which contains natural pores, and a lower layer of highly purified collagen fleece containing hyaluronan (HA).

In this study, the medical device will be used and evaluated in a one-step procedure combining microfracturing with surgical implantation of HYTOP®. HYTOP® will support haemostasis in the articular cartilage defect, act as a support for cell growth and as a three-dimensional scaffold for cell differentiation. HYTOP® will protect the underlying tissue after cartilage debridement and/or microfracturing of the subchondral bone.

The primary working hypothesis is that HYTOP® is safe and suitable as a cell-free matrix to support haemostasis, as a cover for the cartilage lesion and eventually to enhance cartilage regeneration in a one-step surgical procedure.

Inclusion Criteria:

• Male and female patients between 18 and 50 years of age.
• Good general health condition.
• Signed written informed consent.
• General anaesthesia is justifiable for the patient from the medical point of view.
• Focal chondral defects involving the femorotibial compartment of the knee joint localised in only one compartment and not larger than the size of one HYTOP® patch.
• Isolated one-sided chondral lesion.
• Cartilage defect classified as Outerbridge grade 3 or 4.
• Chondral lesions not exceeding through the subchondral bone (intact subchondral bone).
• Nearly intact chondral structure surrounding the defect, specifically Outerbridge grade 2 or less.
• Corresponding joint area classified with maximum Outerbridge grade 2.
• Clinical symptoms in the target joint (pain on walking 100 m of more than 4 on an 11-point numerical scale or swelling or locking or 'giving way').
• Ensured compliance of subjects over the whole study period.

Exclusion Criteria:

• Treatment with any investigational product within 4 weeks prior to study entry.
• Patients with known hypersensitivity to the constituents of the product or any component or procedure used in the study.
• Patients with previous treatment of the study relevant defect site.
• Cartilage lesion is not intact shouldered, has bipolar or corresponding involvement or bipolar 'kissing' lesions.
• Necessity of cartilage repair treatment at bilateral joints.
• Patients with meniscus lesions, total or partial (more than 1/3 of total volume) resected meniscus, limited joint mobility, varus/valgus joint malalignment of more than 5 degrees or insufficient ligament support.
• Inflammatory joint diseases (e.g. rheumatoid arthritis, Bechterew disease, chondromatosis).
• Infection at study relevant site.
• Osteoarthritis, arthrofibrosis or haematopoetic related diseases.
• Study relevant metabolic disease, adipositas (BMI equal to or greater 30 kilogram per square meter).
• Study relevant neoplastic, neurological or mental illness.
• Study relevant autoimmune disease.
• Patients with elevated risk of bleeding.
• Recent history of drug and/or alcohol abuse (within the last 6 months).
• Pregnant or lactating females.
• Participants of childbearing age (pre-menopausal) who do not accept the use of methods of birth control with pearl index more than 1% (e.g. oral contraceptives, vaginal ring, hormone-releasing intrauterine device (IUD), implants, depot syringes, hormone patch, double barrier method, tubal ligation, vasectomised partner,…) during the treatment period and the first 12 weeks of follow-up period.
• Subjects unable to understand informed consent or having a high probability of non compliance to the study procedures and/or non completion of the study according to investigator's judgement (e.g. illiteracy, insufficient knowledge of local language).
• Subjects not capable of contracting and of understanding the nature, risks, significance and implications of the clinical investigation and unable to form a rational intention in the light of these facts.
• Low probability of compliance with after-care rehabilitation scheme.
• Forbidden concomitant treatment affecting the evaluation of study parameters (e.g. oral intake of chondroitin sulfate, glucosamine, piascledine, other i.a. treatments like depot corticosteroids or arthroscopic procedures).