Biology subjects

Zenobi-Wong, M.

Publications and source records attributed to Zenobi-Wong, M..

4 recordsLinked to original sources

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↗

bioRxiv2019

3D bioprinting of architected hydrogels from entangled microstrands

Hydrogels are an excellent biomimetic of the extracellular matrix and have found great use in tissue engineering. Nanoporous monolithic hydrogels have limited mass transport, restricting diffusion of key biomolecules. Structured microbead-hydrogels overcome some of these limitations, but suffer from lack of controlled anisotropy. Here we introduce a novel method for producing architected hydrogels based on entanglement of microstrands. The microstrands are mouldable and form a porous structure which is stable in water. Entangled microstrands are useable as bioinks for 3D bioprinting, where they align during the extrusion process. Cells co-printed with the microstrands show excellent viability and augmented matrix deposition resulting in a modulus increase from 2.7 kPa to 780.2 kPa after 6 weeks of culture. Entangled microstands are a new class of bioinks with unprecedented advantages in terms of scalability, material versatility, mass transport, showing foremost outstanding properties as a bioink for 3D printed tissue grafts.

bioengineering↗

bioRxiv2019

Nanocomposite bioink exploits dynamic covalent bonds between nanoparticles and polysaccharides for precision bioprinting

The field of bioprinting has made significant recent progress towards engineering tissues with increasing complexity and functionality. It remains challenging, however, to develop bioinks with optimal biocompatibility and good printing fidelity. Here, we demonstrate enhanced printability of a polymer-based bioink based on dynamic covalent linkages between nanoparticles (NPs) and polymers, which retains good biocompatibility. Amine-presenting silica NPs (ca. 45 nm) were added to a polymeric ink containing oxidized alginate (OxA). The formation of reversible imine bonds between amines on the NPs and aldehydes of OxA lead to significantly improved rheological properties and high printing fidelity. In particular, the yield stress increased with increasing amounts of NPs (14.5 Pa without NPs, 79 Pa with 2 wt% NPs). In addition, the presence of dynamic covalent linkages in the gel provided improved mechanical stability over 7 days compared to ionically crosslinked gels. The nanocomposite ink retained high printability and mechanical strength, resulting in generation of centimetre-scale porous constructs and an ear structure with overhangs and high structural fidelity. Furthermore, the nanocomposite ink supported both in vitro and in vivo maturation of bioprinted gels containing chondrocytes. This approach based on simple oxidation can be applied to any polysaccharide, thus the widely applicability of the method is expected to advance the field towards the goal of precision bioprinting.

bioengineering↗

bioRxiv2019

Morphogenesis guided by 3D patterning of growth factors in biological matrices

Three-dimensional (3D) control over the placement of bioactive cues is fundamental to understand cell guidance and develop engineered tissues. Two-photon patterning (2PP) provides such placement at micro- to millimeter scale, but non-specific interactions between proteins and functionalized extracellular matrices (ECMs) restrict its use. Here we report a 2PP system based on non-fouling hydrophilic photocages and Sortase A-based enzymatic coupling offering unprecedented orthogonality and signal-to-noise ratio in both inert hydrogels and complex mammalian matrices. Improved photocaged peptide synthesis, and protein functionalization protocols with broad applicability are introduced. Importantly, the method enables 2PP in a single step and in the presence of fragile biomolecules and cells. As a corollary, we demonstrate the guidance of axons through 3D-patterned nerve growth factor (NGF) within brain-mimetic ECMs. Our approach allows for the interrogation of the role of complex signaling molecules in 3D matrices, thus helping to better understand biological guidance in tissue development and regeneration.

bioengineering↗