Traditional methods for polymer processing involve the use of hazardous organic solvents which may compromise the biological function of scaffolds in tissue engineering. Indeed, the toxic effect of them on biological microenvironment has a tremendous impact on cell fate so altering the main activities involved in in vitro tissue formation. To date, extensive researches focus on seeking newer methods for bio-safely processing polymeric biomaterials to be implanted in the human body. Here, we aim at over viewing two approaches based on solvent free or green solvent based processes in order to identify alternative solutions to fabricate bio-inspired scaffolds to be successfully used in regenerative and degenerative medicine.