Freeze‐Drying as a Novel Biofabrication Method for Achieving a Controlled Microarchitecture within Large, Complex Natural Biomaterial Scaffolds

Abstract

The biofabrication of large natural biomaterial scaffolds into complex 3D shapes which have a controlled microarchitecture remains a major challenge. Freeze-drying (or lyophilization) is a technique used to generate scaffolds in planar 3D geometries. Here we report the development of a new biofabrication process to form a collagen-based scaffold into a large, complex geometry which has a large height to width ratio, and a controlled porous microarchitecture. This biofabrication process is validated through the successful development of a heart valve shaped scaffold, fabricated from a collagen-glycosaminoglycan co-polymer. Notably, despite the significant challenges in using freeze-drying to create such a structure, the resultant scaffold has a uniform, homogenous pore architecture throughout. This is achieved through optimization of the freeze-drying mold and the freezing parameters. We believe this to be the first demonstration of using freeze-drying to create a large, complex scaffold geometry with a controlled, porous architecture for natural biomaterials. This study validates the potential of using freeze-drying for development of organ-specific scaffold geometries for tissue engineering applications, which up until now might not have been considered feasible.

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“…The main advantages of freeze-drying are the ability to regulate pore size from 20 to approximately 300 µm by the change of freezing procedure as well as the possibility to obviate high temperature. In turn, long timescale, high energy consumption, and the possibility to generate irregular pore size constitute the drawbacks of this method [123,[221][222][223][224]. Electrospinning is more complicated technique in which electrostatic forces are used for formation of thin fibers from polymer solution.…”

Oxidized Cashew Gum Scaffolds for Tissue Engineering

“…Comparatively to the aforementioned techniques, freeze‐drying provides the scaffolds with a homogeneous and uniform porous architecture, that can be further predefined and controlled, by adjusting the freezing temperatures and polymer concentration . Importantly, by using this approach physical and/or chemical crosslinking strategies can be employed to tune the material stiffness, which is an attractive parameter to predict different cell functions such as differentiation.…”

Platelet‐derived growth factor stabilises vascularisation in collagen‐glycosaminoglycan scaffolds in vitro

“…Porous collagen–glycosaminoglycan (CG) biomaterials have shown high biocompatibility, high porosity, and homogenous pore size distribution and are biodegradable with non‐toxic degradation products (Brougham et al, ). Despite their successful application, these scaffolds can suffer from core necrosis after implantation in vivo in certain applications (Lyons et al, ).…”