The osteochondral defects(OCDs)resulting from the treatment of giant cell tumors of bone(GCTB)often present two challenges for clinicians:tumor residue leading to local recurrence and non-healing of OCDs.Therefore,thi...The osteochondral defects(OCDs)resulting from the treatment of giant cell tumors of bone(GCTB)often present two challenges for clinicians:tumor residue leading to local recurrence and non-healing of OCDs.Therefore,this study focuses on developing a double-layer PGPC-PGPH scaffold using shell-core structure nanofibers to achieve“spatiotemporal control”for treating OCDs caused by GCTB.It addresses two key challenges:eliminating tumor residue after local excision and stimulating osteochondral regeneration in non-healing OCD cases.With a shell layer of protoporphyrin IX(PpIX)/gelatin(GT)and inner cores containing chondroitin sulfate(CS)/poly(lactic-co-glycolic acid)(PLGA)or hydroxyapatite(HA)/PLGA,coaxial electrospinning technology was used to create shell-core structured PpIX/GT-CS/PLGA and PpIX/GT-HA/PLGA nanofibers.These nanofibers were shattered into nano-scaled short fibers,and then combined with polyethylene oxide and hyaluronan to formulate distinct 3D printing inks.The upper layer consists of PpIX/GT-CS/PLGA ink,and the lower layer is made from PpIX/GT-HA/PLGA ink,allowing for the creation of a double-layer PGPC-PGPH scaffold using 3D printing technique.After GCTB lesion removal,the PGPC-PGPH scaffold is surgically implanted into the OCDs.The sonosensitizer PpIX in the shell layer undergoes sonodynamic therapy to selectively damage GCTB tissue,effectively eradicating residual tumors.Subsequently,the thermal effect of sonodynamic therapy accelerates the shell degradation and release of CS and HA within the core layer,promoting stem cell differentiation into cartilage and bone tissues at the OCD site in the correct anatomical position.This innovative scaffold provides temporal control for anti-tumor treatment followed by tissue repair and spatial control for precise osteochondral regeneration.展开更多
基金supported by the National Natural Science Foundation of China(82302395 and 82001979)Natural Science Foundation of Shanghai(22YF1437400)+6 种基金Young Elite Scientists Sponsorship Program by CAST(2023QNRC001)Shandong Provincial Natural Science Foundation(Major Basic Research Program,ZR2019ZD38)Taishan Scholar Program of Shandong Province(To Huitang Xia,202211333)Natural Science Foundation of Shandong Province(ZR2020MH381)Academic Promotion Program of Shandong First Medical University(2019LJ005)Shandong First Medical University Culture Foundation(202201-09)Social Science Planning and Research Project of Shandong Province(21CTQJ08).
文摘The osteochondral defects(OCDs)resulting from the treatment of giant cell tumors of bone(GCTB)often present two challenges for clinicians:tumor residue leading to local recurrence and non-healing of OCDs.Therefore,this study focuses on developing a double-layer PGPC-PGPH scaffold using shell-core structure nanofibers to achieve“spatiotemporal control”for treating OCDs caused by GCTB.It addresses two key challenges:eliminating tumor residue after local excision and stimulating osteochondral regeneration in non-healing OCD cases.With a shell layer of protoporphyrin IX(PpIX)/gelatin(GT)and inner cores containing chondroitin sulfate(CS)/poly(lactic-co-glycolic acid)(PLGA)or hydroxyapatite(HA)/PLGA,coaxial electrospinning technology was used to create shell-core structured PpIX/GT-CS/PLGA and PpIX/GT-HA/PLGA nanofibers.These nanofibers were shattered into nano-scaled short fibers,and then combined with polyethylene oxide and hyaluronan to formulate distinct 3D printing inks.The upper layer consists of PpIX/GT-CS/PLGA ink,and the lower layer is made from PpIX/GT-HA/PLGA ink,allowing for the creation of a double-layer PGPC-PGPH scaffold using 3D printing technique.After GCTB lesion removal,the PGPC-PGPH scaffold is surgically implanted into the OCDs.The sonosensitizer PpIX in the shell layer undergoes sonodynamic therapy to selectively damage GCTB tissue,effectively eradicating residual tumors.Subsequently,the thermal effect of sonodynamic therapy accelerates the shell degradation and release of CS and HA within the core layer,promoting stem cell differentiation into cartilage and bone tissues at the OCD site in the correct anatomical position.This innovative scaffold provides temporal control for anti-tumor treatment followed by tissue repair and spatial control for precise osteochondral regeneration.