29. Jahrestagung der Deutschen Gesellschaft für Biomaterialien

Prof. Dr.

Chair

Professor

PD Dr.

Dr. Dr.

A new 3D printable bioink of alginate/cellulose hydrogel loaded with thrombocyte concentrate

Biofabrication

Tissue regeneration/regenerated medicine

Abstract text (incl. figure legends and references) With 3D bioprinting, methods are available in the clinical field to produce targeted bioactive constructs for a wide range of applications. Using an autologous platelet concentrate, injectable platelet rich fibrin (i-PRF), which is widely used in the clinical field, it is possible to improve the bioavailability of a conventional alginate/cellulose hydrogel and thus to achieve cellular support. The aim was to further develop an existing hydrogel into a bioink using an autologous platelet concentrate to improve cell viability and proliferation of co-incubated and incorporated cells, through the release of entrapped growth factors. To provide cells with an optimal three-dimensional matrix, a hydrogel of sodium alginate and methylcellulose was loaded with i-PRF and targeted constructs were created using pneumatic extrusion in a bioprinter. Hydrogels were printed, which were subsequently incubated with cells (osteoblasts and HUVECs), as well as gels which were loaded and printed with cells. Cell viability and proliferation were investigated by AlamarBlue assay and fluorescence microscopy and growth factor release by ELISA. In addition, CAM (chorio allantoic membrane) assays were performed to investigate possible pro-angiogenic potential in vivo. Significantly higher cell viability was observed for both cell types on and in the printed i-PRF hydrogel models compared to native gels based on PBS. The high cell viability over several days could be due to the measured constant growth factor release. Visual evaluation of GFP-transduced cells on and in the models using fluorescence microscopy also highlighted an increase in cell proliferation. The CAM assays performed supported the presumed proangiogenic potential of i-PRF hydrogel by a positive effect on total vessel length and mean vessel thickness. The advanced hydrogel shows a positive influence on various tissue cells and could be particularly useful in complex clinical areas such as targeted tissue reconstruction.

Short Talk

Fibrin-dextran hydrogels with tunable porosity and mechanical properties

Cell-material interactions

Abstract text (incl. figure legends and references) The increased use of hydrogels in scaffolds for cells, bioprinting materials, or drug delivery carriers has increased the demand for novel macromolecular building blocks to tune their structure and properties. Conventional natural hydrogels based on collagen or fibrin are limited by their weak mechanical properties and fast degradation rate, while hydrogels based on synthetic polymers face issues with biocompatibility and biodegradation. Therefore, the combination of natural and synthetic polymers is an interesting approach to design hydrogels with the best combination of properties for biomedical applications. A novel biobased hydrogel can be formed by using fibrin and the biopolymer dextran to control the mechanical properties. In this work, we synthesized fibrin and dextran with glycidyl methacrylate (dextran-MA)-based interpenetrating hydrogel networks with tailorable mechanical properties, controlled degradation, and variable pore sizes, which have the ability to support cell proliferation. Obtained hydrogels consist of two networks resulting from the in-situ gelation and crosslinking of fibrinogen and dextran-MA by adding thrombin and dithiothreitol. By varying the amounts and ratio of the precursor&quot;s fibrinogen, dextran-MA and crosslinker dithiolthreitol, hydrogels with high mechanical stability, retarded degradation rates and controlled fibre orientation could be achieved. Swelling experiments and NMR diffusometry measurements showed that the water uptake and mesh sizes of fabricated hydrogels decrease with the increase of dextran-MA concentrations. Imaging methods, such as 2-photon microscopy and cryo-SEM, were utilized to visualise fibrin-dextran hydrogels and determine the fibre thickness. The mesh sizes were determined based on these results and using 1H-NMR diffusometry. Cell viability tests with L929 mouse fibroblasts and human mesenchymal stem cells (MSC) were performed.

Fabrication of functional, biocompatible and biodegradable biomaterials by 3D printing of cellulose nanofiber-filled chitosan hydrogel constructs for tissue engineering applications

Additive manufacturing (e. g. 3D printing)

Abstract text (incl. figure legends and references) Introduction The tissue engineering field favors the development of biomaterials that can support cell growth and regeneration, while being biocompatible, mechanically functional, biodegradable. Hydrogel biomaterials have lots of biomedical applications, like in wound healing, cartilage repair, organ regeneration. Objectives We aim to develop functional hydrogels, which mimic tissue extracellular matrix by combining cellulose nanofibers (CNF) and chitosan (CHI) hydrogel in extrusion 3D printing. Materials &amp; methods The flow behavior of CNF-filled CHI suspensions was investigated by rheology. The mechanical properties of the printed CHI/CNF hydrogels was study by tensile testing. Fibroblast cells viability was assessed by LIVE/DEAD assays. CNF biodegradation was enzymatically studied during cell culture. Results CNFs improved the extrudability of CHI-based inks, resolution, stability of printed constructs. The Newtonian viscosity of CHI-based inks increased at adding the CNFs. The nanofibers improved gelation and mechanical properties of printed hydrogels, in systems of low CHI and CNF concentrations. Young"s modulus and strength as high as 3.0 MPa and 1.5 MPa, respectively, were achieved for hydrogels of c(CHI) of 2% and CNF content of 0.4%. Cell adhesion, proliferation and 3D cell growth was observed within the constructs. Cellulase-laden CHI/CNF scaffolds were also printed, allowing controlled biodegradation of hydrogels. The CNF biodegradation contributed to the sustained formation of pores in the CHI/CNF constructs, allowing cells for controlled infiltration and enhanced 3D cell growth. Conclusion The results are promising for the successful engineering of functional tissues. Design strategies for natural smart biomaterials, which are mechanically-performant, biocompatible, presenting controlled degradability for 3D cell growth were proposed. The developed biomaterials are expected to significantly impact tissue engineering and regenerative medicine.

Understanding degradation and mechanical performance of hyperelastic polylactide copolymers through bulk and ultrathin film analysis correlation

Clinical applications and translation

Abstract text (incl. figure legends and references) Introduction Degradable polyesters such as polyglycolide, polylactide, and poly(ε-caprolactone) have been extensively used in biomedicine.Their high crystallinity, and in some cases high Tg, prevents easy deformability and high limit of elastic recovery. Recently, hyperelasticity was shown in poly[(L-lactic acid)-co-caprolactone] (PLLAcoCL), blended with poly(D-lactic acid) (PDLA).1Understanding the mechanisms of degradation, as well as controlling the degradation rate and mechanical properties, are of importance for developing applications for such (bio)degradable polyesters.2 Objectives Simultaneous measurement of degradation profiles and mechanical properties of PLLAcoCL/PDLA blends in a controlled environment at different pH values, oxidative conditions, or presence of enzymes. Materials and Methods Electrospun meshes, and 30x15x0.1mm films of PLLAcoCL/PDLA (95:5) were prepared for bulk hydrolytic degradation in PBS at 37°C over a time period of 4 months. Moreover, ultrathin films of PLLAcoCL,PDLA,and blends (95:5, 90:10, 85:15, and 80:20) were prepared and degraded at the air-liquid interface using the Langmuir technique coupled with interfacial rheology. The ultrathin films are degraded by the addition of proteinase K (0. 02µg/ml), 3% hydrogen peroxide, hydrochloric acid (0.3M), or potassium hydroxide (pH12). Results Ultrathin films degrade fastest with KOH and H2O2, while degradation with proteinase K was slowest.The shear strength of the films rapidly reduced preceding the phase of rapid mass loss. No degradation-induced crystallization was observed. Bulk degradation took longer, but followed the same behavior. Conclusion Hyperelastic PLLAcoCL/PDLA blends showed hydrolytic, oxidative, and enzymatic degradability with a predictable change in mechanical properties. Langmuir film degradation experiments align in trend for the rate of degradation with bulk experiments enabling faster studies. Nanomaterials2021 Macromolecular Rapid Communications2019

Material design of polymer composites with shape-changing capability for medical applications – Comparison of shape memory polymers and liquid crystal elastomers

Implant associated

Abstract text (incl. figure legends and references) INTRODUCTION Shape-changing polymers that adapt to defects in vivo or work as actuators are extremely promising for novel therapies. They must meet a number of requirements, including biocompatibility, low activation temperatures, and high actuation forces. Therefore, this work aimed for the development of shape memory polymers (SMPs) and liquid crystal elastomers (LCEs) fibers with specifically modified activation temperatures through material design. EXPERIMENTAL METHODS SMPs consist of a permanent and a temporary phase for which TPU and PCL of different molecular weights were used, respectively. LCEs were prepared by hydrosilation of the elastomer PMHS and liquid crystal MBB with three different crosslinkers: 11UB, CHDM-di, and PDMS (vinyl-terminated). Thermal, mechanical, and actoric properties of SMPs and LCEs were determined by DSC and cyclic actuation measurements. RESULTS AND DISCUSSION For SMPs, reducing the molecular weight of the switching phase (PCL) results in a significantly lowered activation temperature. For LCEs, a correlation between molecular length of the crosslinker and activation temperature was expected, but could not be shown. However, by adjusting LC to crosslinker ratio a minimal activation temperature was achieved. The activation temperature of SMPs could be reduced significantly to ~20 °C while LCE needed &gt;60 °C to actuate. Material composition-dependent actuation behavior of SMPs and LCEs was characterized and compared. CONCLUSION The generated data shows promising properties for future smart medical applications for both SMPs and LCEs. The ability to design low activation temperatures in SMPs enables applications in vivo while high actuation forces qualify LCEs for ex vivo usage. ACKNOWLEDGMENTS This research (projects 21022BR, 21970BR, 20322BR) is funded through the AiF within the program for supporting the &quot;Industrielle Gemeinschaftsforschung (IGF)&quot; from funds of the BMWK on the basis of a decision by the German Bundestag.

Lecture hall 7

Short Talks 16

Biofabrication / Hydrogels

Short Talk Session

Short Talks 16
Biofabrication / Hydrogels

Termin

Chair

Thema

Programm

Short Talks 16Biofabrication / Hydrogels

Termin

Chair

Thema

Programm

Short Talks 16
Biofabrication / Hydrogels