Controlled-release hydrogel loaded with magnesium-based nanoflowers synergize immunomodulation and cartilage regeneration in tendon-bone healing

Tendon-bone interface injuries pose a significant challenge in tissue regeneration,necessitating innovative approaches.Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries.In this study,we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions(Mg^(2+)).We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles(Mg-PC)through a self-assembly process and integrated them into a two-component hydrogel.The hydrogel was composed of dopamine-modified hyaluronic acid(Dop-HA)and F127.To ensure controlled release and mitigate the“burst release”effect of Mg^(2+),we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel.This crosslinking strategy extended the release window of Mg^(2+)concentrations for up to 56 days.The resulting hydrogel(Mg-PC@Dop-HA/F127)exhibited favorable properties,including injectability,thermosensitivity and shape adaptability,making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites.Furthermore,the hydrogel sustained the release of Mg^(2+)and Procyanidins,which attracted mesenchymal stem and progenitor cells,alleviated inflammation,and promoted macrophage polarization towards the M2 phenotype.Additionally,it enhanced collagen synthesis and mineralization,facilitating the repair of the tendon-bone interface.By incorporating multilevel metal phenolic networks(MPN)to control ion release,these hybridized hydrogels can be customized for various biomedical applications.

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.

Exosome-loaded extracellular matrix-mimic hydrogel with anti-inflammatory property Facilitates/promotes growth plate injury repair

Growth plate cartilage has limited self-repair ability,leading to poor bone bridge formation post-injury and ultimately limb growth defects in children.The current corrective surgeries are highly invasive,and outcomes can be unpredictable.Following growth plate injury,the direct loss of extracellular matrix(ECM)coupled with further ECM depletion due to the inhibitory effects of inflammation on the cartilage matrix protein greatly hinder chondrocyte regeneration.We designed an exosome(Exo)derived from bone marrow mesenchymal stem cells(BMSCs)loaded ECM-mimic hydrogel to promote cartilage repair by directly supplementing ECM and anti-inflammatory properties.Aldehyde-functionalized chondroitin sulfate(OCS)was introduced into gelatin methacryloyl(GM)to form GMOCS hydrogel.Our results uncovered that GMOCS hydrogel could significantly promote the synthesis of ECM due to the doping of OCS.In addition,the GMOCS-Exos hydrogel could further promote the anabolism of chondrocytes by inhibiting inflammation and ultimately promote growth plate injury repair through ECM remodeling.