title: Effect of biodegradation and de novo matrix synthesis on the mechanical properties of valvular interstitial cell-seeded polyglycerol sebacate-polycaprolactone scaffolds.
abstract: The development of living heart valves that grow with the patient is a promising strategy for heart valve replacements in pediatric patients. Despite active research in the field of tissue engineered heart valves there have been limited efforts to optimize the balance between biodegradation of the scaffolds and de novo extracellular matrix (ECM) synthesis by cells and study their consequences on the mechanical properties of the cell-seeded construct. This study investigates the effect of in vitro degradation and ECM secretion on the mechanical properties of hybrid polyester scaffolds. The scaffolds were synthesized from blends of fast degrading polyglycerol sebacate (PGS) and slowly degrading polycaprolactone (PCL). PGS-PCL scaffolds were electrospun using a 2:1 ratio of PGS to PCL. Accelerated hydrolytic degradation in 0.1 mM sodium hydroxide revealed 2-fold faster degradation of PGS-PCL scaffolds compared with PCL scaffolds. Thermal analysis and scanning electron microscopy demonstrated marginal change in PCL scaffold properties, while PGS-PCL scaffolds showed preferential mass loss of PGS and thinning of the individual fibers during degradation. Consequently, the mechanical properties of PGS-PCL scaffolds decreased gradually with no significant change for PCL scaffolds during accelerated degradation. Valvular interstitial cells (VICs) seeded on PGS-PCL scaffolds showed higher ECM protein secretion compared with PCL. Thus the mechanical properties of the cell-seeded PCL scaffolds did not change significantly compared with acellular scaffolds, probably due to slower degradation and ECM deposition by VICs. In contrast, the PGS-PCL scaffolds exhibited a gradual decrease in the mechanical properties of the acellular scaffolds due to degradation, which was compensated for by new matrix secreted by VICs seeded on the scaffolds. Our study demonstrated that the faster degrading PGS component of PGS-PCL accelerated the degradation rate of the scaffolds. VICs, on the other hand, were able to remodel the synthetic scaffold, depositing new matrix proteins and maintaining the mechanical properties of the scaffolds.
authors.affiliation: Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Sant
authors.forename: Dharini
authors.initials: D
authors.lastname: Iyer
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Gaharwar
authors.forename: Alpesh
authors.initials: A
authors.lastname: Patel
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001705:Bioprosthesis; D002478:Cells, Cultured; D019245:Compressive Strength / Q000502:physiology; D003651:Decanoates / Q000737:chemistry; D055119:Elastic Modulus / Q000502:physiology; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005109:Extracellular Matrix / Q000737:chemistry*; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D006350:Heart Valve Prosthesis; D008943:Mitral Valve / Q000166:cytology* / Q000502:physiology*; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013314:Stress, Mechanical; D013552:Swine; D023822:Tissue Engineering / Q000295:instrumentation; D054457:Tissue Scaffolds
chemical_list: D003651:Decanoates; D011091:Polyesters; D011108:Polymers; C469892:poly(glycerol-sebacate); C016240:polycaprolactone; D005990:Glycerol