3D Culture Models . Articular Cartilage. Bone . Bone Marrow . Intervertebral Disc . Tendon

Tissue Engineering

Our research centers on creating advanced 3D cell culture systems by combining interdisciplinary approaches across cell biology, engineering technologies and materials science. These platforms are designed to mimic complex tissue environments to help us investigating key biological processes in tissue development, disease and regeneration.

The main focus of our group is the development of cartilage, tendon and bone/bone marrow tissues. These engineered systems not only serve as research models but also enable the generation of functional grafts for tissue repair in clinical applications. The expertise developed within the group has also been implemented beyond musculoskeletal targets in collaborations across other fields, including tumor modelling.

Cartilage tissue engineering and regeneration (Project Lead: PD Dr. Karoliina Pelttari «LINK»)

Our goal is to develop innovative therapies to repair cartilage defects using grafts engineered from autologous cells. Here, we have identified nasal chondrocytes (NC) as a particularly promising cell source with a remarkable capacity to robustly generate cartilage. NC also display features of environmental plasticity, allowing them to genetically and functionally adapt to the knee jointenvironment following implantation.

We are currently investigating the capacity of NC to regulate main pathological processes activated in a joint by inflammation and abnormal loading, as characteristic in osteoarthritis. We also investigate how pre-conditioning of NC influences their ability to adapt to even more hostile tissue environments, such as present in degenerated intervertebral discs (collaboration with Cartilage Engineering group). In the framework of an ERC Synergy project (collaboration with Filippo Rijli, FMI), we target understanding the molecular and epigenetic mechanisms endowing NC with their distinct functionalities.

In collaboration with the Cartilage Engineering group of Andrea Barbero «LINK», we translate this reseach on the potential of NC into clinical solutions for patients suffering from traumatic cartilage injuries and osteoarthritis. Through advanced tissue engineering, we create personalized grafts from a patient’s own nasal cells—offering a promising alternative to conventional treatments and paving the way for long-term joint regeneration. Our concept of generating a cartilage graft using autologous nasal chondrocytes has been translated into a first-in-man study for the treatment of focal cartilage defects in the knee (Fig.1). We have further coordinated a follow-up multicenter phase II trial (Bio-Chip), funded under the EU-Horizon2020 program. In 2025 we have started two multi center phase II clinical studies to treat patellofemoral osteoarthritis: the SNF-funded PFOA study «LINK» and ENCANTO «LINK» (Engineered CArtilage from the Nose to the Treatment of Osteoarthritis), funded under the EU-Horizon HLTH program. See also «Connection to clinical practive».

Bone and bone marrow engineering (Project Lead: Dr. Andres Garcia-Garcia«LINK»)

Our goal is the controlled development of 3D bone/bone marrow tissues using human cells, to be applied as models to study human hematopoiesis and as grafts for bone regeneration.

Combining mesenchymal stromal cells with scaffolding materials and dynamic 3D cell culture, we have engineered in vitro different models of human bone marrow (Figure 3A). These systems were exploited to expand cord blood hematopoietic stem and progenitor cells, and study blood malignancies such as acute myeloid leukemia and myeloproliferative neoplasms. These engineered tissues were also applied to model solid tumors metastasis in bone (e.g. breast and prostate cancer) (collaborations with Mohamed Bentires-Aji and Clementine Le Magnen). Engineered human bone marrow systems have shown patterns of niche-mediated resistance to drugs or immunotherapies that could not be mimicked by using 2D cultures or simple 3D spheroids. Current efforts are dedicated to: (i) generate standardized models using human induced pluripotent stem cells (collaboration with Barbara Treutlein), (ii) apply them to investigate the interactions between blood cancer cells and their microenvironment (collaborations with Petya Apostolova and Judith Zaugg), (iii) increase throughput for larger scale tests in miniaturized compartments, and (iV) develop patient-specific tissues for personalized medicine approaches.

We demonstrated that mesenchymal stromal cells from human bone marrow and adipose tissue can not only directly differentiate into osteogenic cells, but they can also recapitulate the developmental process of endochondral ossification. This involves the formation of cartilaginous intermediate tissues which robustly and efficiently remodel into functional bone organs upon in vivo implantation (Figure 3B).

In a long-term collaboration with the Bone Regeneration group of Arnaud Scherberich «LINK» and following a developmental engineering concept, we generated cell-based devitalized osteoinductive extracellular matrices for bone (re)generation (collaboration with Paul Bourgine). Moreover, we exploited the vasculogenic potential of human adipose tissue-derived cells and their capacity to recapitulate endochondral ossification to engineer vascularized bone grafts for challenging clinical settings such as humerus fractures, maxilla reconstruction, symbrachydactyly or infected long bones (See “Connection to clinical practice”).

Tendon biology and engineering (Project Lead: PD Dr. Karoliina Pelttari «LINK»)

Our research is dedicated on understanding the fundamental biology of tendon in both health and disease, with the aim to indentify mechanisms that regulate tissue homeostasis, degeneration and repair (collaboration Andreas M. Müller).

We are particularly interested in the role of cellular senescence in these processes. While this phenomenon is generally described to naturally occur in aging tissues, we have identified their accumulation also in younger patients with different types of tendinopathies (Fig 2). Additionally, we are investigating the role of cellular metabolism in tendon regeneration. Using a custom-designed 3D bioreactor system that replicates both non-physiological or physiological strain, we are currently exploring how modulating senescence or metabolism can influence tendon regeneration. Through these aproaches, we aim to identfy potential targets to enhance tendon healing and repair in patients with different types of tendonopathies.

Connection to clinical practice

Prof. Florian M. Thieringer, Prof. Andreas M. Müller, Prof. Dirk J. Schaefer, Prof. Stefan Schaeren

Maxillofacial Surgery - Orthopaedics and Traumatology - Plastic, Reconstructive, Aesthetic and Hand Surgery - Spinal Surgery

Engineered cellular grafts for regenerative surgery

Facial and tracheal cartilage reconstruction.

Engineered nasal cartilage grafts, previously successfully used for reconstruction of the alar lobule of the nose, are being investigated for the reconstruction of the nasal cartilage septum after perforation (Martin Haug, Benedict Kaiser). Studies are ongoing to explore the use of epithelialized cartilage grafts for the management of empty nose syndromes (Simona Negoias) and/or tracheal defects (Didier Lardinois)

Articular cartilage and intervertebral disc repair.

Following the demonstration of feasibility and safety of nasal chondrocyte-based engineered cartilage for the treatment of knee cartilage injuries, a phase II study (total of 108 patients in 5 international centers) to investigate efficacy was recently completed (Marcus Mumme). In 2025 initiated multi center phase II clinical studies currently investigate the treatment of an extended set of orthopaedic indications using engineered nasal cartilage (Marcus Mumme, Florian Imhoff). Pre-clinical studies are also exploring the use of nasal chondrocytes to engraft in intervertebral discs and slow down their degeneration (Arne Mehrkens).

Bone repair

Treatment of humerus fractures in elderly individuals previously indicated the safety and biological functionality of stromal vascular fraction (SVF) cells intraoperatively derived from autologous adipose tissue. Grafts based on SVF cells are currently being investigated for axially-vascularized bone graft prefabrication in the reconstruction of the maxilla (Claude Jaquiery, Tarek Ismail, AlexanderHaumer), for symbrachydactyly (Alexandre Kämpfen) and for infected long bone defects (Rik Osinga, Martin Clauss, Mario Morgenstern).