A porous tissue engineering scaffold selectively degraded by cell-generated reactive oxygen species.
Biodegradable tissue engineering scaffolds are commonly fabricated from poly(lactide-co-glycolide) (PLGA) or similar polyesters that degrade by hydrolysis. PLGA hydrolysis generates acidic breakdown products that trigger an accelerated, autocatalytic degradation mechanism that can create mismatched rates of biomaterial breakdown and tissue formation. Reactive oxygen species (ROS) are key mediators of cell function in both health and disease, especially at sites of inflammation and tissue healing, and induction of inflammation and ROS are natural components of the in vivo response to biomaterial implantation. Thus, polymeric biomaterials that are selectively degraded by cell-generated ROS may have potential for creating tissue engineering scaffolds with better matched rates of tissue in-growth and cell-mediated scaffold biodegradation. To explore this approach, a series of poly(thioketal) (PTK) urethane (PTK-UR) biomaterial scaffolds were synthesized that degrade specifically by an ROS-dependent mechanism. PTK-UR scaffolds had significantly higher compressive moduli than analogous poly(ester urethane) (PEUR) scaffolds formed from hydrolytically-degradable ester-based diols (p < 0.05). Unlike PEUR scaffolds, the PTK-UR scaffolds were stable under aqueous conditions out to 25 weeks but were selectively degraded by ROS, indicating that their biodegradation would be exclusively cell-mediated. The in vitro oxidative degradation rates of the PTK-URs followed first-order degradation kinetics, were significantly dependent on PTK composition (p < 0.05), and correlated to ROS concentration. In subcutaneous rat wounds, PTK-UR scaffolds supported cellular infiltration and granulation tissue formation, followed first-order degradation kinetics over 7 weeks, and produced significantly greater stenting of subcutaneous wounds compared to PEUR scaffolds. These combined results indicate that ROS-degradable PTK-UR tissue engineering scaffolds have significant advantages over analogous polyester-based biomaterials and provide a robust, cell-degradable substrate for guiding new tissue formation.
Biomedical Engineering, Vanderbilt University, 5824 Stevenson Center, PMB 351631, Nashville, TN 37235-1631, USA.
John R
JR
Martin
Biomedical Engineering, Vanderbilt University, 5824 Stevenson Center, PMB 351631, Nashville, TN 37235-1631, USA.
Mukesh K
MK
Gupta
Chemical and Biomolecular Engineering, Vanderbilt University, 2301 Vanderbilt Place, VU Station B #351604, Nashville, TN 37235-1604, USA.
Jonathan M
JM
Page
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Fang
F
Yu
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Medical Research Service, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37212, USA.
Jeffrey M
JM
Davidson
Chemical and Biomolecular Engineering, Vanderbilt University, 2301 Vanderbilt Place, VU Station B #351604, Nashville, TN 37235-1604, USA.
Scott A
SA
Guelcher
Biomedical Engineering, Vanderbilt University, 5824 Stevenson Center, PMB 351631, Nashville, TN 37235-1631, USA. Electronic address: craig.duvall@vanderbilt.edu.
Craig L
CL
Duvall
D000818:Animals; D001672:Biocompatible Materials; D002384:Catalysis; D019344:Lactic Acid / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014947:Wounds and Injuries / Q000628:therapy
D001672:Biocompatible Materials; D017382:Reactive Oxygen Species; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
Biodegradation; Macrophage; Oxidation; Polyurethane; Scaffold; Wound healing