Solvent-Free Approaches for the Processing of Scaffolds in Regenerative Medicine

Abstract

The regenerative medicine field is seeking novel strategies for the production of synthetic scaffolds that are able to promote the in vivo regeneration of a fully functional tissue. The choices of the scaffold formulation and the manufacturing method are crucial to determine the rate of success of the graft for the intended tissue regeneration process. On one hand, the incorporation of bioactive compounds such as growth factors and drugs in the scaffolds can efficiently guide and promote the spreading, differentiation, growth, and proliferation of cells as well as alleviate post-surgical complications such as foreign body responses and infections. On the other hand, the manufacturing method will determine the feasible morphological properties of the scaffolds and, in certain cases, it can compromise their biocompatibility. In the case of medicated scaffolds, the manufacturing method has also a key effect in the incorporation yield and retained activity of the loaded bioactive agents. In this work, solvent-free methods for scaffolds production, i.e., technological approaches leading to the processing of the porous material with no use of solvents, are presented as advantageous solutions for the processing of medicated scaffolds in terms of efficiency and versatility. The principles of these solvent-free technologies (melt molding, 3D printing by fused deposition modeling, sintering of solid microspheres, gas foaming, and compressed CO2 and supercritical CO2-assisted foaming), a critical discussion of advantages and limitations, as well as selected examples for regenerative medicine purposes are herein presented.

Advances in Tissue Engineering Approaches for Craniomaxillofacial Bone Reconstruction

“…Therefore, E-factors (the actual amount of waste product produced in the process per gram of product) and low carbon footprint methods are the two parameters that deserve attention. Thus, processing technologies such as melt molding (compression, injection and extrusion molding); 3D printing; fused deposition modeling; sintering of solid particles (heat, compressed CO 2 and selective laser sintering); gas foaming and compressed or supercritical CO 2 foaming, operating in the absence of solvent during assembly of 3D scaffolds, present ideal strategies for development of medicated scaffolds [11].…”

“…The principle of gas foaming is to generate pores in a polymeric matrix through a nucleation-growth mechanism of gas bubbles that results in formation of microporous material after venting out of the bubbles. This process is compatible with both hydrophobic and hydrophilic polymeric matrices and is usually performed under mild temperatures [11]. This solvent free technique consists of 3 steps…”

“…Sodium Bicarbonate and Ammonium Bicarbonate or physical blowing agent e.g. inert gas -Nitrogen, Argon or Carbon dioxide) [11].…”

“…Thus, extensive research is required to achieve reconstruction of such craniofacial and dental tissue defects [10]. The reconstruction therapy for critical bone defects should address the post-surgical side effects of slow or deficient bone recovery, graft rejection and low osseointegration [11].…”

Comparison of Scaffolds Fabricated via 3D Printing and Salt Leaching: In Vivo Imaging, Biodegradation, and Inflammation

“…Various printers have been developed to fabricate 3D scaffolds. Thermal melting printers are referred to as fused deposition modeling (FDM) printers, and they have come into widespread use [ 19 ]. FDM printers can produce 3D scaffolds without organic solvents by transforming flowing bioinks into solid structures at an ambient temperature.…”