Designing for Degradation: Strategies for Resorption in 3D Printed Medical Devices

Abstract

Rib fractures and critical-sized segmental bone defects represent significant clinical challenges in orthopedic trauma due to high morbidity, limited regenerative capacity, and shortcomings in current treatment options. The standard treatment of most rib fracture cases is limited to pain control and respiratory support, with the surgical stabilization of rib fractures (SSRF) using titanium plates reserved for severely injured patients. Although SSRF has been shown to improve long-term patient outcomes, its expanded use has been limited by the invasiveness of the procedure and a lack of safe and effective resorbable fixation materials. Similarly, existing clinical standards for the treatment of segmental bone defects, such as autografts and allografts, are limited by tissue availability, donor site morbidity, and risk of infection, presenting a substantial unmet clinical need for bone graft alternatives. Additive manufacturing of resorbable polymeric resins represents a promising approach to address unmet needs in medical device fabrication as a route to access customizable, complex geometries. Herein, we first present a materials strategy based on fumarate-based copolyester–hydroxyapatite (HAp) composite thiol-ene networks enabled by continuous liquid interface production (CLIP) for the fabrication of implantable orthopedic devices and demonstrate preclinical efficacy in vivo. 3D printed fumarate-based copolyester-composite osteosynthetic plates were assessed for the surgical stabilization of rib fractures (SSRF) in a rabbit rib fracture model. Compared to rigid titanium fixation plates, ribs fixed with 3D printed composite plates elicit fracture calluses with decreased inflammatory response, enhanced osseointegration, and bone morphometry at 2- and 4-weeks post-fracture comparable to clinically used titanium plates. Additionally, fumarate-based copolyester-composites were fabricated into fully resorbable triply periodic gyroid scaffolds, and the mechanics under compressive loading were tuned by varying gyroid porosity and design. Bone ingrowth and remodeling was assessed in a load sharing rabbit radial segmental defect model at 4 and 12 weeks. Microcomputed tomography and histological evaluation show copolyester-composite scaffolds lead to significantly improved bone deposition and endochondral ossification across the defect sites compared to untreated controls, unfilled fumarate-based copolyester and 3D printed titanium scaffolds. Taken together, this work represents a marked improvement over commercially available orthopedic implants with respect to fixation devices and synthetic bone graft alternatives for the restoration of native bone volume in segmental defects. To address limitations in achievable degradation rates of 3D printed devices to date, silyl ether-based multifunctional thiol crosslinkers were developed as generalizable approach to accelerating degradation in 3D printed thiol-ene copolyester networks. Silyl ether-crosslinked networks demonstrate tunable degradation profiles dependent on both crosslinking chemistry and copolyester backbone composition with modular control over mechanical properties. Additionally, assessments of network degradation by mechanical property loss over time are shown to offer a framework for predictable degradation in 3D printed copolyester networks.