Advances in the Fabrication of Biomaterials for Gradient Tissue Engineering

Despite breakthroughs in tissue engineering, a tremendous problem still lies in repairing the interfacial tissue which connects soft tissue to hard tissue, particularly cartilage–bone, tendon/ligament–bone, and cementum–ligament–bone interfaces. The challenge comes from the complicated biophysical and biochemical characteristics of interfacial tissues, involving a graded variation of chemical components, structures, and mechanical properties as well as a heterogeneous cell distribution from the soft end to the hard end. Accordingly, significant progress has been made in the design of hierarchical and heterogeneous hydrogel systems in order to solve this problem. Advanced programmable technologies, such as 3D printing and microfluidic platforms, have shown potential in constructing templates or scaffolds with tissue-specific characteristics. The structural specialty of the three aforementioned interfacial tissues is summarized in this review. Then the text concentrates on how to utilize different scale hydrogels (from chemical variation, nanoscale, microscale to cellular regulation) to fabricate gradient constructions for regenerating interfacial tissues, together with in vitro and in vivo outcomes. In particular, the fabrication of continuous gradients is highlighted in this review. Promisingly, the versatile designs involved in fabricating hierarchical and heterogeneous hydrogel systems are predicted to tackle the unsolved problems, and this interfacial tissue engineering methodology is expected to expand its use in therapeutic applications.

Hierarchical and heterogeneous hydrogel system as a promising strategy for diversified interfacial tissue regeneration.

Tissue patterning is the result of complex interactions between transcriptional programs and various mechanical cues that modulate cell behaviour and drive morphogenesis. Vertebrate Hedgehog signalling plays key roles in embryogenesis and adult tissue homeostasis, and is central to skeletal development and the osteogenic differentiation of mesenchymal stem cells. The expression of several components of the Hedgehog signalling pathway have been reported to be mechanically regulated in mesodermal tissue patterning and osteogenic differentiation in response to external stimulation. Since a number of bone developmental defects and skeletal diseases, such as osteoporosis, are directly linked to aberrant Hedgehog signalling, a better knowledge of the regulation of Hedgehog signalling in the mechanosensitive bone marrow-residing mesenchymal stromal cells will present novel avenues for modelling these diseases and uncover novel opportunities for extracellular matrix-targeted therapies. In this review, we present a brief overview of the key molecular players involved in Hedgehog signalling and the basic concepts of mechanobiology, with a focus on bone development and regeneration. We also highlight the correlation between the activation of the Hedgehog signalling pathway in response to mechanical cues and osteogenesis in bone marrow-derived mesenchymal stromal cells. Finally, we propose different tissue engineering strategies to apply the expanding knowledge of 3D material-cell interactions in the modulation of Hedgehog signalling in vitro for fundamental and translational research applications. 

https://doi.org/10.1016/j.mtbio.2022.100502

From mesenchymal niches to engineered in vitro model systems: Exploring and exploiting biomechanical regulation of vertebrate hedgehog signalling

A perspective on the wet spinning process and its advancements in biomedical sciences

One-dimensional photonic crystals (1D PhCs) obtained by aluminium anodizing under oscillating conditions are promising materials with structure-dependent optical properties. Electrolytes based on sulphuric, oxalic, and selenic acids have been utilized for the preparation of anodic aluminium oxide (AAO) 1D PhCs with sub-100-nm pore diameter. AAO films with larger pores can be obtained by anodizing in phosphorous acid at high voltages. Here, for the first time, anodizing in phosphorous acid is applied for the preparation of AAO 1D PhCs with nonbranched macropores. The sine wave profile of anodizing voltage in the 135–165 V range produces straight pores, whose diameter is above 100 nm and alternates periodically in size. The pore diameter modulation period linearly increases with the charge density by a factor of 599 ± 15 nm·cm2·C−1. The position of the photonic band gap is controlled precisely in the 0.63–1.96 µm range, and the effective refractive index of AAO 1D PhCs is 1.58 ± 0.05.

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One-Dimensional Photonic Crystals with Nonbranched Pores Prepared via Phosphorous Acid Anodizing of Aluminium

Porous biodegradable scaffolds have many applications in bioengineering, ranging from cell culture and transplantation, to support structures, to induce blood vessel and tissue formation in vivo. While numerous strategies have been developed for the manufacture of porous scaffolds, it remains challenging to control the spatial organization of the pores. In this study, we introduce the use of the granular convection effect, also known as the muesli or brazil nut effect, to rapidly engineer particulate templates with a vertical size gradient. These templates can then be used to prepare scaffolds with pore size gradients. To demonstrate this approach, we prepared templates with particle size gradients, which were then infused with a prepolymer solution consisting of the pentaerythritol ethoxylate (polyol), sebacoyl chloride (acid chloride), and poly(caprolactone). Following curing, the template was dissolved to yield biodegradable polyester-ether scaffolds with pore size gradients that could be tuned depending on the size range of the particulates used. The application of these scaffolds was demonstrated using pancreatic islets, which were loaded via centrifugation and retained within the scaffold's pores without a decrease in viability. The proposed strategy provides a facile approach to prepare templates with spatially organized pores that could potentially be used for cell transplantation, or guided tissue formation.

Facile preparation of tissue engineering scaffolds with pore size gradients using the muesli effect and their application to cell spheroid encapsulation

Nanoporous anodic alumina (NAA) is an emerging platform material for photonics and light-based applications. However, demonstrations of narrow bandwidth lasing emissions from this optical material remain limited. Here, we demonstrate that narrow bandwidth NAA-based gradient-index filters (NAA-GIFs) can be optically engineered to achieve high-quality visible lasing. NAA-GIFs fabricated by a modified sinusoidal pulse anodization approach feature a well-resolved, intense, high-quality photonic stopband (PSB). The inner surface of NAA-GIFs is functionalized with rhodamine B (RhoB) fluorophore molecules through micellar solubilization of sodium dodecyl sulfate (SDS) surfactant. Systematic variation of the ratio of SDS and RhoB enables the precise engineering of the light-emitting functional layer to maximize light-driven lasing associated with the slow photon effect at the red edge of NAA-GIFs’ PSB. It is found that the optimal surfactant-to-fluorophore ratio, namely, 20 mM SDS to 0.81 mM RhoB, results in a strong, polarized lasing at ∼612 nm. This lasing was characterized by a remarkably high-quality–gain product of ∼536, a Purcell factor of 2.2, a lasing threshold of ∼0.15 mJ per pulse, and a high-quality polarization ratio of ∼0.7. Our results benefit the advancement of the NAA-based lasing technology for a variety of photonic disciplines such as sensing, tweezing, light harvesting, and photodetection. 

Lasing from Narrow Bandwidth Light-Emitting One-Dimensional Nanoporous Photonic Crystals

The hemispherical barrier oxide layer (BOL) closing the bottom tips of hexagonally distributed arrays of cylindrical nanochannels in nanoporous anodic alumina (NAA) membranes is structurally engineered by anodizing aluminum substrates in three distinct acid electrolytes at their corresponding self-ordering anodizing potentials. These nanochannels display a characteristic ionic current rectification (ICR) signal between high and low ionic conduction states, which is determined by the thickness and chemical composition of the BOL and the pH of the ionic electrolyte solution. The rectification efficiency of the ionic current associated with the flow of ions across the anodic BOL increases with its thickness, under optimal pH conditions. The inner surface of the nanopores in NAA membranes was chemically modified with thiol-terminated functional molecules. The resultant NAA-based iontronic system provides a model platform to selectively detect gold metal ions (Au3+) by harnessing dynamic ICR signal shifts as the core sensing principle. The sensitivity of the system is proportional to the thickness of the barrier oxide layer, where NAA membranes produced in phosphoric acid at 195 V with a BOL thickness of 232 ± 6 nm achieve the highest sensitivity and low limit of detection in the sub-picomolar range. This study provides exciting opportunities to engineer NAA structures with tailorable ICR signals for specific applications across iontronic sensing and other nanofluidic disciplines.

Satyathiran Gunenthiran

Papers

Facile preparation of tissue engineering scaffolds with pore size gradients using the muesli effect and their application to cell spheroid encapsulation

Lasing from Narrow Bandwidth Light-Emitting One-Dimensional Nanoporous Photonic Crystals

Structural Engineering of the Barrier Oxide Layer of Nanoporous Anodic Alumina for Iontronic Sensing.

Engineering of Solid-State Random Lasing in Nanoporous Anodic Alumina Photonic Crystals