Buoyancy‐Driven Gradients for Biomaterial Fabrication and Tissue Engineering

Abstract

The controlled fabrication of gradient materials is becoming increasingly important as the next generation of tissue engineering seeks to produce inhomogeneous constructs with physiological complexity. Current strategies for fabricating gradient materials can require highly specialized materials or equipment, and cannot be generally applied to the wide range of systems used for tissue engineering. In this report, the fundamental physical principle of buoyancy was exploited as a generalized approach for generating materials bearing well-defined compositional, mechanical or biochemical gradients. Gradient formation was demonstrated across a range of different materials (e.g. polymers, hydrogels) and cargos (e.g. liposomes, nanoparticles, extracellular vesicles, macromolecules, small molecules). As well as versatility, this buoyancy-driven gradient approach also offers speed (<1 min) and simplicity (a single injection) using standard laboratory apparatus. Moreover, this technique was readily applied to a major target in complex tissue engineering: the osteochondral interface. A bone morphogenetic protein 2 gradient, presented across a gelatin methacryloyl hydrogel laden with human mesenchymal stem cells, was used to locally stimulate osteogenesis and mineralization and produce integrated osteochondral tissue constructs. The versatility and accessibility of this fabrication platform should ensure widespread applicability and provide opportunities to generate other gradient materials or interfacial tissues.

Gradient Hydrogels—The State of the Art in Preparation Methods

“…Again, liquid hydrogel precursors are mixed in a controlled manner to create a non-isotropic liquid mixture and then crosslinking of this mixture follows. An example of this is the buoyancy approach by Li et al, which should be suitable for generating hydrogels with well-defined compositional, mechanical, or biochemical gradients [24]. This simple method can be applied when (liquid) hydrogel precursors of different density exist or can be prepared using a suitable modifier.…”

“…Schematic showing the steps of gradient formation: (i) an ase layer (yellow) is added to a mold, (ii) the injection phase (purple) is introduced during a single injection at a controlled rate, (iii) the system is allowed to equilibrate and form a material gradient, and (iv) the gradient is preserved by gelling or polymerizing the material. Reprinted from [24] with permission.…”

“…The gradient pattern could be tuned by varying the injection rate and concentration of sucrose in the base layer. Reprinted from [24] with permission. The initial gradient is preserved by subsequent gelation.…”

Autologous Versatile Vesicles‐Incorporated Biomimetic Extracellular Matrix Induces Biomineralization

“…[ 60–63 ] However, current studies involving EVs delivery systems mainly focus on the synthetic hydrogels or matrix. [ 64–66 ] Notably, polymers that are not water‐soluble may not be suitable to encapsulate EVs, and the residual unreacted cross‐linkers for hydrogel making increase the potential toxicity. [ 67 ] In addition, the processing of these polymers normally involves a strong organic solvent, which may degrade the structural integrity and content of the exosomes when mixed.…”

Advances in the Application of Biomimetic Endometrium Interfaces for Uterine Bioengineering in Female Infertility

“…In addition to direct cell loading in the scaffolds, many strategies are focused on the surface or structure modification for better biocompatibility and stronger absorption for cell attachment and delivery of bioactive growth factors, hormones and extracellular vesicles (Li C. et al, 2019;Shadish et al, 2019). Bacterial cellulose (BC) is a biocompatible and water adsorbable bacteria scaffold.…”