Regenerating critical-sized long bone defects poses substantial challenges due to limitations of autografts and processed allografts.Biomaterial scaffolds offer versatile alternatives,yet their effectiveness is often ...Regenerating critical-sized long bone defects poses substantial challenges due to limitations of autografts and processed allografts.Biomaterial scaffolds offer versatile alternatives,yet their effectiveness is often constrained by their limited innate osteoinductivity.While growth factors and cells can enhance osteoinduction,the inclusion of biologics in biomaterial scaffolds creates regulatory challenges for clinical translation.To address this,here we describe three-dimensional(3D)printed polycaprolactone(PCL)scaffolds for temporally controlled delivery of osteoimmunomodulatory amorphous calcium phosphate-chitosan nanoparticles(ACPC-NP).In vitro,the ACPC-NP exhibit concentration dependent effects on osteoblasts,monocytes,and osteoclasts.At increasing concen-trations up to 500μg/ml,these nanoparticles stimulate osteogenesis,modulate M2/M1 macrophage polarization,and inhibit osteoclast maturation and activity.Leveraging these concentration-dependent effects in vivo through temporally controlled release of ACPC-NP from 3D-printed PCL scaffolds,we observe the complete regeneration and the restoration of biomechanical strength of critically sized radial defects in rats.Such healing is absent in defects implanted with bare PCL scaffolds or those loaded with calcium-phosphate microparticles.The tunable osteoimmunomodulation by the NP underscores the translational potential of this technology to yield struc-turally sound and functionally robust bone regeneration outcomes.展开更多
基金supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award numbers P50AR072000(HAA),P30AR069655(HAA)the Musculoskeletal Transplant Foundation(HAA)the AO Foundation Clinical Priority Program(HAA).
文摘Regenerating critical-sized long bone defects poses substantial challenges due to limitations of autografts and processed allografts.Biomaterial scaffolds offer versatile alternatives,yet their effectiveness is often constrained by their limited innate osteoinductivity.While growth factors and cells can enhance osteoinduction,the inclusion of biologics in biomaterial scaffolds creates regulatory challenges for clinical translation.To address this,here we describe three-dimensional(3D)printed polycaprolactone(PCL)scaffolds for temporally controlled delivery of osteoimmunomodulatory amorphous calcium phosphate-chitosan nanoparticles(ACPC-NP).In vitro,the ACPC-NP exhibit concentration dependent effects on osteoblasts,monocytes,and osteoclasts.At increasing concen-trations up to 500μg/ml,these nanoparticles stimulate osteogenesis,modulate M2/M1 macrophage polarization,and inhibit osteoclast maturation and activity.Leveraging these concentration-dependent effects in vivo through temporally controlled release of ACPC-NP from 3D-printed PCL scaffolds,we observe the complete regeneration and the restoration of biomechanical strength of critically sized radial defects in rats.Such healing is absent in defects implanted with bare PCL scaffolds or those loaded with calcium-phosphate microparticles.The tunable osteoimmunomodulation by the NP underscores the translational potential of this technology to yield struc-turally sound and functionally robust bone regeneration outcomes.
