Twin Screw Extrusion Based Technologies Offer Novelty, Versatility, Reproducibility and Industrial Scalability for Fabrication of Tissue Engineering Scaffolds

Introduction

Porous, biodegradable and bioresorbable polymeric scaffolds are utilized in a variety of tissue engineering applications and so are shaped typically via 3-D printing, solvent casting, particulate leaching, phase separation, gas foaming, freeze drying, electrospinning and solidform fabrication. However, significant restrictions and issues stay in the polymers and additives which you can use, cost, reproducibility of the real estate and microstructure of the fabricated scaffolds, and scalability of the fabrication functions to realistic manufacturing costs. These remaining major issues require the production of alternative materials processing methods. Recently, numerous novel fabrication methods in line with the twin screw extrusion method have already been developed and were found in the fabrication of different types of scaffolds for cells engineering, especially concentrating on bone and cartilage applications. These new functions integrate twin screw extrusion with spiral winding, electrospinning and co-extrusion and offer significant positive aspects over conventional methods of scaffold fabrication. These advantages include reproducibility, versatility and commercial scalability.

Challenges found in Fabrication of Scaffolds for Cells Engineering

Tissue engineering depends on the use of porous, bioresorbable and biodegradable polymeric scaffolds to promote cell proliferation, differentiation, migration and extracellular matrix generation. Important conditions that need to be considered for scaffold development involve suitability of the top biocompatibility and properties, kinetics of biodegradation, and micro structural requirements such as porosity, pore size, and pore interconnectivity. The conventional methods that are used to fabricate tissue engineering scaffolds include 3-D printing, solvent casting, particulate leaching, phase separation, gas foaming, freeze drying, electrospinning and solid-form fabrication. In spite of the significant developments made over the last decade significant issues and restrictions remain in the polymers and additives which you can use, expense, reproducibility of the microstructure and real estate of the fabricated scaffolds, and scalability of the fabrication operations to realistic manufacturing prices. These remaining major problems require the advancement of alternative materials and materials processing options for scaffold fabrication. Recently, numerous novel fabrication methods in line with the twin screw extrusion process have been developed and had been used in the fabrication of different types of scaffolds for cells engineering applications. These brand-new operations integrate twin screw extrusion with spiral winding, co-extrusion and electrospinning and offer significant advantages over standard ways of scaffold fabrication. These advantages include commercial scalability, reproducibility and versatility.

Advantages Provided by Twin Screw Extrusion for Fabrication of Scaffolds

Twin screw extrusion procedures (two screws rotating in the contrary, i.e., counter-rotating or same, we.e., co-rotating guidelines), that is fully-intermeshing, or non-intermeshing, are very versatile and scalable constant processing functions that generate reproducible mixtures and extrudates within rigid dimensional and structural tolerances. Twin screw extrusion allows multiple unit operations, including solids conveying, melting, distributive, and dispersive blending of nanoparticles and contaminants, deaeration, and shaping of the scaffolds, to occur within the confines of an individual process. The screws generally have modular designs, which allow the concomitant usage of multiple screw elements with several functionalities, i.e., regularflighted conveying screws (both right-handed and left-handed) and lenticular components, i.e., the kneading disks. The kneading disks can be staggered at numerous stagger stagger and angles guidelines to supply a dispersive mixing ability, which permits the break-up of particle clusters, i.e., a ability not within conventional scaffold fabrication methods. A die that is crafted to extrude the required scaffold shape is mounted on the front-end of the twin screw extruder.

Twin Screw Extrusion Based Systems for Fabrication of Cells Engineering Scaffolds

The twin screw extrusion based technologies which are recently produced for the fabrication of tissue engineering scaffolds principally consist of five different fabrication methods. They are:

1. Twin screw extrusion and die combination

2. Twin screw co-extrusion and extrusion

3. Twin screw extrusion and spiral winding

4. Twin screw electrospinning and extrusion

5. Twin screw extrusion, spiral and electrospinning winding

All five strategies are amenable to industrial scale-up and generate scaffolds which are reproducible in geometry and properties. Most of these five strategies can also be used with and without solvents (dried out versus wet extrusion methods). All five methods have been applied in the region of interface cells engineering, targeting regenerative medicine just for cartilage and bone service and regeneration.

For processes #1-3, different polymeric resins including Poly(Glycolic Acid) (PGA), Poly(Lactic Acid) (PLA), and Poly(Caprolactone) (PCL) are compounded in the twin screw extruder with one or more porogens involving dissolvable salts and polymers, physical (typically supercritical CO2) or chemical substance blowing agents to facilitate the development of a porous structure. Various bioactives including nanoparticles, medications, and proteins can be incorporated also. A die with a geometry that is designed to enable the change of the plastic extrusion mixture within the twin screw extruder right into a desired shape is connected to the twin screw extruder. A co-extrusion die can also be used to permit multiple layers involving differences in materials of construction, porosity, composition to get formed into scaffolds. For instance, a co-extrudable cage/ main structure features been targeted for use in spinal arthrodesis. The twin screw extrusion and spiral winding method integrates the twin screw extrusion process with a altered filament winding technique (designated here as ¡®¡®spiral winding¡¯¡¯). The extrudate emerging from the die is usually wound around a mandrel that concomitantly rotates and translates sideways creating a helical and spiral trajectory for the fabrication of cylindrical extrudates. Scaffolds with a wide range of sizes and thicknesses, and radial and axial distributions of pore size and porosity can be developed utilizing the twin screw extrusion and spiral winding technique, especially addressing the necessities for relatively large critical bone defects .

In techniques #4 and #5, the twin-screw extruder is included with the electrospinning process. The electrospun mesh is normally porous and the porosity could be controlled via the manipulation of the voltage (commonly 10-30 kV), the spinning distance between the spinneret and the conductive area, the use of a rotating mandrel with a conductive surface, the flow rate, temperature, and the perfect solution is concentration, when a wet spinning method is used. The spinneret die might have multichannels for circulation to enable the boost of the production pace. The twin screw extrusion and electrospinning method generates nanofibrous meshes that may be incorporated with various types of bioactives to focus on the generation of specifically interface tissues, including the bone and cartilage user interface. The electrospinning process may also be wedded to the spiral winding procedure for the fabrication of multi-featured scaffolds which contain a spiral wound shell around an electrospun core. Such hybrid functions are suitable for fabricating multiscale scaffolds to engineer vascularized osteon-like structures.

Usage of Twin Screw Extrusion Based Scaffold Fabrication Methods for Functional Grading

Finally, it should be noted that all of these methods (#1-5) possess the capability to introduce various elements of the formulation/s in a timedependent fashion into the twin screw extruder for the manufacture of spatially (radially and axially) graded, i.e., ¡°functionally-graded¡± scaffolds. The availability of such graded scaffolds permits the control of the spatial distributions of bioactives even more, porosity, pore sizes, mechanical properties and the cells engineering practitioners with further functions for mimicking the complicated elegance of native tissues.

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