Neration. Huge efforts have been created around the exploration of approaches to prepare bioactive scaffolds. Within the previous five years, electrospun scaffolds have gained an exponentially escalating reputation within this location due to their ultrathin fiber diameter and massive surface-volume ratio, which is favored for biomolecule delivery. This paper testimonials existing approaches that can be used to prepare bioactive electrospun scaffolds, such as physical adsorption, blend electrospinning, coaxial electrospinning, and covalent immobilization. Also, this paper also analyzes the existing challenges (i.e., protein instability, low gene transfection efficiency, and issues in correct kinetics prediction) to attain biomolecule release from electrospun scaffolds, which necessitate additional investigation to totally exploit the biomedical applications of these bioactive scaffolds. Crucial WORDS electrospinning . gene delivery . protein delivery . scaffold . tissue engineeringW. Ji : Y. Sun : F Yang : J. J. J. P van den Beucken : J. A. Jansen () . . Division of Biomaterials (Dentistry 309) Radboud University Nijmegen Health-related Center PO Box 9101, 6500 HB, Nijmegen, The Netherlands e-mail: [email protected] W. Ji : Y. Sun : M. Fan : Z. Chen Important Laboratory for Oral Biomedical DYRK4 Inhibitor custom synthesis engineering of Ministry of Education, College and Hospital of Stomatology, Wuhan University 237 Luoyu Road 430079, Wuhan, Hubei Province, People’s Republic of ChinaABBREVIATIONS ALP alkaline phosphatase BMP2 bone morphogenic protein two (protein form) bmp2 bone morphogenic protein two (gene type) BSA bovine serum albumin EGF epidermal growth issue FA folic acid HA hyaluronic acid HAp hydroxylapatite NGF nerve growth factor pBMP-2 plasmid DNA encoding bone morphogenic protein-2 PCL poly(-caprolactone) PCL-b-PEG poly(-caprolactone)-block-poly(ethylene glycol) pCMV-EGFP plasmid DNA encoding enhanced green fluorescent protein with a cytomegalovirus promoter pCMV plasmid DNA encoding -galactosidase PDGF-bb platelet-derived growth factor-bb PDLLA poly (D,L-lactide) pDNA plasmid deoxyribonucleic acid PEG-b-PDLLA poly (ethylene glycol)-block-poly(D,L-lactide) pEGFP-N1 plasmid DNA encoding a red shifted variant of wild-type green fluorescent protein pGL3 plasmid DNA encoding luciferase PLCL poly(L-lactide-co-epsilon-caprolactone) PLGA poly(lactide-co-glycolide) PMMAAA copolymer of methyl methacrylate (MMA) and acrylic acid (AA) PSU polysulphone PVA poly(vinyl alcohol)Ji et al.INTRODUCTION Tissue engineering is definitely an interdisciplinary field that applies the principles of engineering and life sciences toward the improvement of functional substitutes for broken tissues. The basic notion behind tissue engineering will be to utilize the body’s natural biological response to tissue damage in conjunction with engineering principles (1). To achieve profitable tissue regeneration, 3 crucial aspects are to be considered: cells, scaffolds, and D3 Receptor Agonist drug biomolecules (e.g., growth issue, gene, etc.). Presently, two techniques have emerged because the most promising tissue engineering approaches (Fig. 1) (2). One particular will be to implant pre-cultured cells and synthetic scaffold complexes into the defect location. Within this approach, the seeded cells are commonly isolated from host target tissues, for which they provide the principle resource to kind newly born tissue. The synthetic scaffolds, however, deliver porous three-dimensional structures to accommodate the cells to form extracellular matrix (ECMs) and regulate the cell.