Abstract
A major challenge in orthopedics is the repair of large non-union bone fractures. A promising therapy for this indication is the use of biodegradable bioinspired biomaterials that stabilize the fracture site, relieve pain and initiate bone formation and healing. This study uses a multidisciplinary evaluation strategy to assess immunogenicity, allergenicity, bone responses and physicochemical properties of a novel biomaterial scaffold. Two-photon stereolithography generated personalized custom-built scaffolds with a repeating 3D structure of Schwarz Primitive minimal surface unit cell with a specific pore size of ∼400 μm from three different methacrylated poly(d,l-lactide-co-ε-caprolactone) copolymers with lactide to caprolactone monomer ratios of 16 : 4, 18 : 2 and 9 : 1. Using in vitro and in vivo assays for bone responses, immunological reactions and degradation dynamics, we found that copolymer composition influenced the scaffold physicochemical and biological properties. The scaffolds with the fastest degradation rate correlated with adverse cellular effects and mechanical stiffness correlated with in vitro osteoblast mineralization. The physicochemical properties also correlated with in vivo bone healing and immune responses. Overall these observations provide compelling support for these scaffolds for bone repair and illustrate the effectiveness of a promising multidisciplinary strategy with great potential for the preclinical evaluation of biomaterials.
Highlights
A major challenge in orthopedics is the repair of large non-union bone fractures
LCM3 and M controls induced a similar number of differentiated tartrate-resistant acid phosphatase (TRAP)+ OCs compared to LCM4, though only LCM4 was statistically significantly higher compared to LCM6.1 ( p < 0.01)
These data demonstrate that LCM6.1 significantly reduced OC differentiation compared to the other tested groups
Summary
A major challenge in orthopedics is the repair of large non-union bone fractures. A promising therapy for this indication is the use of biodegradable bioinspired biomaterials that stabilize the fracture site, relieve pain and initiate bone formation and healing. A porous three-dimensional (3D) scaffold for bone repair ideally should mimic an autologous bone graft,[14] be biodegradable and either induce minimal inflammation or no inflammation, in combination with the factors that promote bone repair and should not cause fibrosis or scarring.[15] Examples of biodegradable polymers that are resorbed overtime frequently used in regenerative medicine[16,17,18] include polyglycolic acid (PGA), polylactide (PLA), polylactic-co-glycolic acid (PLGA), poly-ε-caprolactone (PCL), poly(D,L-lactide) (PDLLA) and additional copolymers and composites.[19,20] scaffold degradation is beneficial, undesired effects caused by degradation products via the formation of small chain carboxylic acids may change the local pH and cause inflammation[21,22] or in some cases as occurs within PLA, acidic degradation products may be toxic.[17] Methods developed for the production of these porous polymeric materials include electrospinning, phase separation and porogen leaching These techniques do not enable the manufacture of complex 3D structures with tunable micro-scale features
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