Entwicklung eines Knochenklebstoffes auf Polymerbasis
Zusammenfassung der Projektergebnisse
Tyramine-modified bioadhesives based on hyaluronic acid or gelatin candidate as attractive biomaterials for various medical applications. In this study Gelatin-tyramine (GT) was examined as bone adhesive that could facilitate reconstruction of highly comminuted fractures, whereas tyramine-modified hyaluronic acid (HAT) was optimized as an injectable cell carrier system for cartilage defect repair. In both bioconjugates the physico-chemical properties were highly tunable by varying the degree of tyramine-substitution and the crosslinker concentration of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). Cytocompatibility was proven for both bioconjugates, which mainly depended on the H2O2 concentration and cell-density used. An optimal HRP/ H2O2 ratio was defined for HAT to encapsulate up to 20x106 human mesenchymal stromal cells (MSCs), but maintaining favorable visco-elastic and biomechanical properties. Due to its fast biodegradability and the ability of peripheral cells to migrate into GT, it was used for biomechanical testing as a bone adhesive. A standardized and highly precise tensile test setup was developed and the tensile strength to cancellous bone was investigated using clinically-like testing conditions. Sole GT resulted in a tensile strength comparable to commercially available fibrin glue, but was decupled by incorporation of αtricalciumphosphates and hydroxyapatite. However, a critical interfacial strength of 0.2 MPa as recommended by Weber et al. was not reached. Further investigation is needed to chemically characterize GT to optimize its content of tyramine substitutes. HAT on the other hand was less suitable as a bone adhesive since it does not allow significant cell migration and degrades slower compared to GT. However, it was demonstrated to provide a favorable environment for mesenchymal stromal cells to differentiate towards chondrocytes by applying dynamic joint-mimicking mechanical loading. HAT was optimized for high-density MSC-encapsulation concomitant to sufficient biomechanical properties that allowed the application of joint-mimicking mechanical loads for 1 month time using a multiaxial-loading bioreactor. It was demonstrated that complex loading induced the production and activation of TGF-b1 and thereby lead to chondrogenic graft maturation without applying any exogenous growth factors. In addition, cellularized HAT was demonstrated to adhere to native cartilage comparable to clinically used fibrin glue. Since joint mechanics can be optimally targeted in the postoperative care, we hypothesize that mechano-resilient HAT hydrogels offer an encouraging biomaterial as injectable cell carrier system in the treatment of cartilage defects.
Projektbezogene Publikationen (Auswahl)
- (2020) Articular Joint-Simulating Mechanical Load Activates Endogenous TGF-β in a Highly Cellularized Bioadhesive Hydrogel for Cartilage Repair. The American journal of sports medicine 48 (1) 210–221
Behrendt, Peter; Ladner, Yann; Stoddart, Martin James; Lippross, Sebastian; Alini, Mauro; Eglin, David; Armiento, Angela Rita
(Siehe online unter https://doi.org/10.1177/0363546519887909) - Tyramine-modified hyaluronan hydrogel for human chondrocyte encapsulation: cell viability, rheological and bioadhesive properties. Swiss Society of Biomaterials and Regenerative Medicine (SSB-RM) 2017, St. Gallen
Behrendt P; Lippross S; Richards RG; Alini M, Eglin M, Armiento AR
- Tyramine-modified hyaluronan hydrogel for mesenchymal strimal cell encapsulation: cell viability and rheological properties. European Chapter Meeting of the Tissue Engineering and Regenerative Medicine International Society (EU TERMIS) 2017, Davos
Behrendt P; Lippross S; Richards RG; Alini M, Eglin M, Armiento AR
