ABSTRACT
The use of granular matrices to support parts during the bioprinting process was first reported by Bhattacharjee et al. in 2015, and since then, several approaches have been developed for the preparation and use of supporting gel beds in 3D bioprinting. This paper describes a process to manufacture microgel suspensions using agarose (known as fluid gels), wherein particle formation is governed by the application of shear during gelation. Such processing produces carefully defined microstructures, with subsequent material properties that impart distinct advantages as embedding print media, both chemically and mechanically. These include behaving as viscoelastic solid-like materials at zero shear, limiting long-range diffusion, and demonstrating the characteristic shear-thinning behavior of flocculated systems. On the removal of shear stress, however, fluid gels have the capacity to rapidly recover their elastic properties. This lack of hysteresis is directly linked to the defined microstructures previously alluded to; because of the processing, reactive, non-gelled polymer chains at the particle interface facilitate interparticle interactions-similar to a Velcro effect. This rapid recovery of elastic properties enables bioprinting high-resolution parts from low-viscosity biomaterials, as rapid reformation of the support bed traps the bioink in situ, maintaining its shape. Furthermore, an advantage of agarose fluid gels is the asymmetric gelling/melting transitions (gelation temperature of ~30 °C and melting temperature of ~90 °C). This thermal hysteresis of agarose makes it possible to print and culture the bioprinted part in situ without the supporting fluid gel melting. This protocol shows how to manufacture agarose fluid gels and demonstrates their use to support the production of a range of complex hydrogel parts within suspended-layer additive manufacture (SLAM).
Subject(s)
Bioprinting , Sepharose , Beds , Biocompatible Materials , DiffusionABSTRACT
[This corrects the article DOI: 10.1063/5.0061361.].
ABSTRACT
Skin exhibits a complex structure consisting of three predominant layers (epidermis, dermis, and hypodermis). Extensive trauma may result in the loss of these structures and poor repair, in the longer term, forming scarred tissue and associated reduction in function. Although a number of skin replacements exist, there have been no solutions that recapitulate the chemical, mechanical, and biological roles that exist within native skin. This study reports the use of suspended layer additive manufacturing to produce a continuous tri-layered implant, which closely resembles human skin. Through careful control of the bioink composition, gradients (chemical and cellular) were formed throughout the printed construct. Culture of the model demonstrated that over 21 days, the cellular components played a key role in remodeling the supporting matrix into architectures comparable with those of healthy skin. Indeed, it has been demonstrated that even at seven days post-implantation, the integration of the implant had occurred, with mobilization of the adipose tissue from the surrounding tissue into the construct itself. As such, it is believed that these implants can facilitate healing, commencing from the fascia, up toward the skin surface-a mechanism recently shown to be key within deep wounds.
ABSTRACT
Alginate is a material that has many biomedical applications due to its low toxicity and a variety of favourable physical properties. In particular, the ease in which hydrogels are formed from alginate and the variety of mechanical behaviours that can be imparted on the hydrogels, by understanding alginate chemistry and intuitive design, has made alginate the most widely investigated polysaccharide used for tissue engineering. This chapter provides an overview of alginate, from how the source and natural variations in composition can influence mechanical properties of alginate hydrogels, through to some innovative techniques used to modify and functionalise the hydrogels designed specifically for cell-based therapies. The main focus is on how these strategies of understanding and controlling the chemistry of alginates have resulted in the development of hydrogels that can be tuned to deliver the physical behaviours required for successful application. This will also highlight how research on the physicochemical properties has helped alginate evolve from a structural polysaccharide in brown seaweed into a highly tuneable, multifunctional, smart biomaterial, which is likely to find further biomedical applications in the future.
