Synergistic rheumatoid arthritis therapy by interrupting the detrimental feedback loop to orchestrate hypoxia M1 macrophage polarization using an enzyme-catalyzed nanoplatform

Rapid and efficient tendon fixation to a bone following trauma or in response to degenerative processes can be facilitated using a tendon anchoring device.Osteomimetic biomaterials,and in particular,bio-resorbable polymer composites designed to match the mineral phase content of native bone,have been shown to exhibit osteoinductive and osteoconductive properties in vivo and have been used in bone fixation for the past 2 decades.In this study,a resorbable,bioactive,and mechanically robust citrate-based composite formulated from poly(octamethylene citrate)(POC)and hydroxyapatite(HA)(POC-HA)was investigated as a potential tendon-fixation biomaterial.In vitro analysis with human Mesenchymal Stem Cells(hMSCs)indicated that POC-HA composite materials supported cell adhesion,growth,and proliferation and increased calcium deposition,alkaline phosphatase production,the expression of osteogenic specific genes,and activation of canonical pathways leading to osteoinduction and osteoconduction.Further,in vivo evaluation of a POC-HA tendon fixation device in a sheep metaphyseal model indicates the regenerative and remodeling potential of this citrate-based composite material.Together,this study presents a comprehensive in vitro and in vivo analysis of the functional response to a citrate-derived composite tendon anchor and indicates that citrate-based HA composites offer improved mechanical and osteogenic properties relative to commonly used resorbable tendon anchor devices formulated from poly(L-co-D,l-lactic acid)and tricalcium phosphate PLDLA-TCP.