Three-dimensional-printed individualized porous implants:A new“implant-bone”interface fusion concept for large bone defect treatment

Bone defect repairs are based on bone graft fusion or replacement.Current large bone defect treatments are inadequate and lack of reliable technology.Therefore,we aimed to investigate a simple technique using three-dimensional(3D)-printed individualized porous implants without any bone grafts,osteoinductive agents,or surface biofunctionalization to treat large bone defects,and systematically study its long-term therapeutic effects and osseointegration characteristics.Twenty-six patients with large bone defects caused by tumor,infection,or trauma received treatment with individualized porous implants;among them,three typical cases underwent a detailed study.Additionally,a large segmental femur defect sheep model was used to study the osseointegration characteristics.Immediate and long-term biomechanical stability was achieved,and the animal study revealed that the bone grew into the pores with gradual remodeling,resulting in a long-term mechanically stable implant-bone complex.Advantages of 3D-printed microporous implants for the repair of bone defects included 1)that the stabilization devices were immediately designed and constructed to achieve early postoperative mobility,and 2)that osseointegration between the host bone and implants was achieved without bone grafting.Our osseointegration method,in which the“implant-bone”interface fusion concept was used instead of“bone-bone”fusion,subverts the traditional idea of osseointegration.

Practical strategy to construct anti-osteosarcoma bone substitutes by loading cisplatin into 3D-printed titanium alloy implants using a thermosensitive hydrogel

Surgical resection and perioperative adjuvant chemotherapy-based therapies have improved the prognosis of patients with osteosarcoma;however,intraoperative bone defects,local tumour recurrence,and chemotherapy-induced adverse effects still affect the quality of life of patients.Emerging 3D-printed titanium alloy(Ti6Al4V)implants have advantages over traditional implants in bone repair,including lower elastic modulus,lower stiffness,better bone conduction,more bone in-growth,stronger mechanical interlocking,and lager drug-loading capacity by their inherent porous structure.Here,cisplatin,a clinical first-line anti-osteosarcoma drug,was loaded into Ti6Al4V implants,within a PLGA-PEG-PLGA thermo-sensitive hydrogel,to construct bone substitutes with both anti-osteosarcoma and bone-repair functions.The optimal concentrations of cisplatin(0.8 and 1.6 mg/mL)were first determined in vitro.Thereafter,the anti-tumour effect and biosafety of the cisplatin/hydrogel-loaded implants,as well as their bone-repair potential were evaluated in vivo in tumour-bearing mouse,and bone defect rabbit models,respectively.The loading of cisplatin reduced tumour volume by more than two-thirds(from 641.1 to 201.4 mm3)with negligible organ damage,achieving better anti-tumour effects while avoiding the adverse effects of systemic cisplatin delivery.Although bone repair was hindered by cisplatin loading at 4 weeks,no difference was observed at 8 weeks in the context of implants with versus without cisplatin,indicating acceptable long-term stability of all implants(with 8.48%-10.04%bone in-growth and 16.94%-20.53%osseointegration).Overall,cisplatin/hydrogel-loaded 3D-printed Ti6Al4V implants are safe and effective for treating osteosarcoma-caused bone defects,and should be considered for clinical use.