Calcium phosphates(CaP)represent an important class of osteoconductive and osteoinductive biomaterials.As proof-of-concept,we show how a multi-component CaP formulation(monetite,beta-tricalcium phosphate,and calcium p...Calcium phosphates(CaP)represent an important class of osteoconductive and osteoinductive biomaterials.As proof-of-concept,we show how a multi-component CaP formulation(monetite,beta-tricalcium phosphate,and calcium pyrophosphate)guides osteogenesis beyond the physiological envelope.In a sheep model,hollow dome-shaped constructs were placed directly over the occipital bone.At 12 months,large amounts of bone(~75%)occupy the hollow space with strong evidence of ongoing remodelling.Features of both compact bone(osteonal/osteon-like arrangements)and spongy bone(trabeculae separated by marrow cavities)reveal insights into function/need-driven microstructural adaptation.Pores within the CaP also contain both woven bone and vascularised lamellar bone.Osteoclasts actively contribute to CaP degradation/removal.Of the constituent phases,only calcium pyrophosphate persists within osseous(cutting cones)and non-osseous(macrophages)sites.From a translational perspective,this multi-component CaP opens up exciting new avenues for osteotomy-free and minimally-invasive repair of large bone defects and augmentation of the dental alveolar ridge.展开更多
The design principle of osteogenic bone grafts has shifted from immunological inertness to limiting foreign body response to combined osteoimmunomodulatory activity to promote high-quality endogenous bone regeneration...The design principle of osteogenic bone grafts has shifted from immunological inertness to limiting foreign body response to combined osteoimmunomodulatory activity to promote high-quality endogenous bone regeneration.Recently developed immunomodulatory mucin hydrogels have been shown to elicit very low complement activation and suppress macrophage release and activation after implantation in vivo.However,their immunoregulatory activity has not yet been studied in the context of tissue repair.Herein,we synthesized mucin-monetite composite materials and investigated their early osteoimmunomodulation using a critical-size rat bone defect model.We demonstrated that the composites can polarize macrophages towards the M2 phenotype at weeks 1 and 2.The early osteoimmunomodulation enhanced early osteogenesis and angiogenesis and ultimately promoted fracture healing and engraftment(revascularization of the host vasculature)at weeks 6 and 12.Overall,we demonstrated the applicability of mucin-based immunomodulatory biomaterials to enhance tissue repair in tissue engineering and regenerative medicine.展开更多
New composites prepared containing nanoscale hydroxyapatite or monetite uniformly distributed in a polyhydroxyalkanoate (polyhydroxybutyrate or polyhydroxybutyrate-hydroxyvalerate) matrix with mass fractions of 1%5...New composites prepared containing nanoscale hydroxyapatite or monetite uniformly distributed in a polyhydroxyalkanoate (polyhydroxybutyrate or polyhydroxybutyrate-hydroxyvalerate) matrix with mass fractions of 1%5% were then injected into dumb-like specimens. The results show that the tensile strength and the tensile modulus of the composites are improved. The microstructures of the composites were observed using transmission electron microscopy (TEM).展开更多
文摘Calcium phosphates(CaP)represent an important class of osteoconductive and osteoinductive biomaterials.As proof-of-concept,we show how a multi-component CaP formulation(monetite,beta-tricalcium phosphate,and calcium pyrophosphate)guides osteogenesis beyond the physiological envelope.In a sheep model,hollow dome-shaped constructs were placed directly over the occipital bone.At 12 months,large amounts of bone(~75%)occupy the hollow space with strong evidence of ongoing remodelling.Features of both compact bone(osteonal/osteon-like arrangements)and spongy bone(trabeculae separated by marrow cavities)reveal insights into function/need-driven microstructural adaptation.Pores within the CaP also contain both woven bone and vascularised lamellar bone.Osteoclasts actively contribute to CaP degradation/removal.Of the constituent phases,only calcium pyrophosphate persists within osseous(cutting cones)and non-osseous(macrophages)sites.From a translational perspective,this multi-component CaP opens up exciting new avenues for osteotomy-free and minimally-invasive repair of large bone defects and augmentation of the dental alveolar ridge.
基金The authors gratefully acknowledge financial support from the National Natural Science Foundation of China(81925027,82002275,32271421)Natural Science Foundation of the Jiangsu Higher Education Institutions of China(20KJB430041)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions,the Swedish Foundation for Strategic Research(Grant No.FFL15-0072)KTH Lifescience platform grant 2021,and Norweigian Research Council(331752).
文摘The design principle of osteogenic bone grafts has shifted from immunological inertness to limiting foreign body response to combined osteoimmunomodulatory activity to promote high-quality endogenous bone regeneration.Recently developed immunomodulatory mucin hydrogels have been shown to elicit very low complement activation and suppress macrophage release and activation after implantation in vivo.However,their immunoregulatory activity has not yet been studied in the context of tissue repair.Herein,we synthesized mucin-monetite composite materials and investigated their early osteoimmunomodulation using a critical-size rat bone defect model.We demonstrated that the composites can polarize macrophages towards the M2 phenotype at weeks 1 and 2.The early osteoimmunomodulation enhanced early osteogenesis and angiogenesis and ultimately promoted fracture healing and engraftment(revascularization of the host vasculature)at weeks 6 and 12.Overall,we demonstrated the applicability of mucin-based immunomodulatory biomaterials to enhance tissue repair in tissue engineering and regenerative medicine.
基金Supported by the Major Research Project of the Ninth-Five Plan of China(No. 96- C0 3 - 0 3 - 0 2)
文摘New composites prepared containing nanoscale hydroxyapatite or monetite uniformly distributed in a polyhydroxyalkanoate (polyhydroxybutyrate or polyhydroxybutyrate-hydroxyvalerate) matrix with mass fractions of 1%5% were then injected into dumb-like specimens. The results show that the tensile strength and the tensile modulus of the composites are improved. The microstructures of the composites were observed using transmission electron microscopy (TEM).
