Biology subjects

Fisch, P.

Publications and source records attributed to Fisch, P..

4 recordsLinked to original sources

bioRxiv2026

Nose-to-Knee Transplantation for Osteochondral Regeneration: A Proof-of-Concept Study in Sheep Employing Ceramic-Hydrogel Osteochondral Grafts

Osteochondral defects remain a major clinical challenge, frequently progressing to osteoarthritis and ultimately requiring joint replacement. Despite advances in regenerative strategies, current approaches often fail to restore the structural and functional complexity of the osteochondral unit, resulting in poor integration and limited long-term performance. Here, we developed autologous osteochondral grafts combining mechanically mature nasal chondrocyte-derived cartilage with a 3D-printed strontium-hardystonite-gahnite trabecular bone scaffold, which was tested in an osteochondral defect model in sheep. Nasal chondrocytes were encapsulated in a hyaluronan transglutaminase-alginate hydrogel generating hyaline-like cartilage with physiologically relevant compressive properties (1.0 +/- 0.2 MPa) after 6 weeks of in vitro maturation. MicroCT scans of the osteochondral unit were used to design biomimetic trabecular bone scaffolds. Controlled infiltration of the hydrogel into the trabecular pores and subsequent cartilage maturation created a mechanical interlock between cartilage and bone layer, reaching an interfacial shear strength of 201 +/- 42 kPa. The translational potential of this approach was evaluated in a proof-of-concept ovine study. The engineered cartilage remained attached to the bone scaffold for three months following implantation, but osteochondral repair was limited by implant sinking, likely caused by inadequate implant fixation in the defect, resulting in micromotion, synovial fluid infiltration, osteolysis and subsequent bone cyst formation. Together, this work demonstrates the feasibility of engineering mechanically mature autologous osteochondral grafts while identifying subchondral bone integration as the primary bottleneck limiting successful osteochondral regeneration and future clinical translation.

bioengineering↗

bioRxiv2026

Benchmarking cartilage regeneration across ten chondrogenic cell sources using native tissue references

A persistent challenge in cartilage tissue engineering is identifying cell sources capable of regenerating cartilage with native-like properties. Variability in chondrogenic potential among human- and animal-derived cells complicates graft development and disease modeling. Here we benchmarked ten chondrogenic cell sources under standardized culture conditions using hyaluronan-alginate biomaterials and implementing a functionality index combining histological and mechanical metrics referenced to native tissue. Mesenchymal stem cells and fetal chondroprogenitors demonstrated superior regenerative capacity, achieving 103% and 95% of native cartilage functionality, respectively. In contrast, adult articular chondrocytes from healthy and osteoarthritic donors produced fibrocartilaginous tissue with functionality scores below 50%. These findings provide a quantitative framework to guide cell source selection and optimize cartilage graft standardization for clinical applications and physiologically relevant disease models, addressing regulatory demands for product characterization.

bioengineering↗

bioRxiv2025

Tissue Engineered Elastic Cartilage-Mimetic Auricular Grafts for Ear Reconstruction

Patients born with microtia, the congenital malformation of the external ear, face substantial psychosocial strain. Current reconstruction relies on harvesting rib cartilage, an invasive procedure associated with donor site morbidity and unnaturally stiff ears due to the use of hyaline cartilage. Tissue engineered auricles could overcome these drawbacks by providing patient-specific elastic cartilage without the need for rib harvest. Yet, key challenges such as fibrocartilage formation, inhomogeneous extracellular matrix formation and mechanical inferiority during ex vivo maturation remain, often leading to graft deformation and degradation in vivo. To address this gap, we integrated approaches maintaining the chondrogenic potential with growth factors, promoting elastic cartilage formation through stress-relaxing materials, and achieving homogeneous maturation by culturing grafts on an elevated bioreactor platform that enables uniform nutrient diffusion, using primary human auricular chondrocytes. Together these approaches resulted in the maturation of bioprinted auricular grafts that closely resemble native human auricular cartilage, demonstrated by the uniform distribution of elastin, glycosaminoglycans, and collagen II, and lack of collagen I. RNA sequencing revealed gene expression patterns consistent with the transition from fibrocartilage towards elastic cartilage. On a functional level, grafts achieved a compressive modulus of 1.1{+/-}0.03 MPa, matching that of native human auricular cartilage (1.0{+/-}0.1 MPa) and maintained their structural integrity for 6 weeks in a subcutaneous rat model, where they transitioned towards mature elastic fibers. These grafts represent the closest approximation of native elastic cartilage achieved ex vivo to date, bringing the field closer to a clinically viable, long-term therapy for children affected by microtia. One-sentence summaryBioprinted auricular grafts develop native-like elastic cartilage and advance towards a durable therapy for children with microtia.

bioengineering↗

bioRxiv2020

Improved accuracy and precision of bioprinting through progressive cavity pump-controlled extrusion

3D bioprinting has seen a tremendous growth in recent years in a variety of fields such as tissue and organ models, drug testing and regenerative medicine. This growth has led researchers and manufacturers to continuously advance and develop novel bioprinting techniques and materials. Although new bioprinting methods are emerging (e.g. contactless and volumetric bioprinting), micro-extrusion bioprinting remains the most widely used method. Micro-extrusion bioprinting, however, is still largely dependent on the conventional pneumatic extrusion process, which relies heavily on homogenous biomaterial inks and bioinks to maintain a constant material flowrate. Augmenting the functionality of the bioink with the addition of nanoparticles, cells or biopolymers can induce inhomogeneities resulting in uneven material flow during printing and/or clogging of the nozzle, leading to defects in the printed construct. In this work, we evaluated a novel extrusion technique based on a miniaturized progressive cavity pump. We compared the accuracy and precision of this system to the pneumatic extrusion system and tested both for their effect on cell viability after extrusion. The progressive cavity pump achieved a significantly higher accuracy and precision compared to the pneumatic system while maintaining good viability and was able to maintain its reliability independently of the bioink composition, printing speed or nozzle size. Progressive cavity pumps are a promising tool for bioprinting and could help provide standardized and validated bioprinted constructs while leaving the researcher more freedom in the design of the bioinks with increased functionality.

bioengineering↗