Three-dimensional printing of biomaterials for bonetissue engineering: a review

Processing biomaterials into porous scaffolds for bone tissueengineering is a critical and a key step in defining and controlling their physicochemical,mechanical,and biological properties.Biomaterials such as polymers are commonlyprocessed into porous scaffolds using conventional processing techniques,e.g.,saltleaching.However,these traditional techniques have shown unavoidable limitations andseveral shortcomings.For instance,tissue-engineered porous scaffolds with a complexthree-dimensional(3D)geometric architecture mimicking the complexity of theextracellular matrix of native tissues and with the ability to fit into irregular tissue defectscannot be produced using the conventional processing techniques.3D printing hasrecently emerged as an advanced processing technology that enables the processing ofbiomaterials into 3D porous scaffolds with highly complex architectures and tunableshapes to precisely fit into irregular and complex tissue defects.3D printing providescomputer-based layer-by-layer additive manufacturing processes of highly precise andcomplex 3D structures with well-defined porosity and controlled mechanical propertiesin a highly reproducible manner.Furthermore,3D printing technology provides anaccurate patient-specific tissue defect model and enables the fabrication of a patientspecifictissue-engineered porous scaffold with pre-customized properties.

Nanotherapeutics for regeneration of degenerated tissue infected by bacteria through the multiple delivery of bioactive ions and growth factor with antibacterial/angiogenic and osteogenic/odontogenic capacity

Therapeutic options are quite limited in clinics for the successful repair of infected/degenerated tissues.Although the prevalent treatment is the complete removal of the whole infected tissue,this leads to a loss of tissue function and serious complications.Herein the dental pulp infection,as one of the most common dental problems,was selected as a clinically relevant case to regenerate using a multifunctional nanotherapeutic approach.For this,a mesoporous bioactive glass nano-delivery system incorporating silicate,calcium,and copper as well as loading epidermal growth factor(EGF)was designed to provide antibacterial/pro-angiogenic and osteo/odontogenic multiple therapeutic effects.Amine-functionalized Cu-doped bioactive glass nanospheres(Cu-BGn)were prepared to be 50–60 nm in size,mesoporous,positive-charged and bone-bioactive.The Cu-BGn could release bioactive ions(copper,calcium and silicate ions)with therapeutically-effective doses.The Cu-BGn treatment to human umbilical vein endothelial cells(HUVEC)led to significant enhancement of the migration,tubule formation and expression of angiogenic gene(e.g.vascular endothelial growth factor,VEGF).Furthermore,the EGF-loaded Cu-BGn(EGF@Cu-BGn)showed pro-angiogenic effects with antibacterial activity against E.faecalis,a pathogen commonly involved in the pulp infection.Of note,under the co-culture condition of HUVEC with E.faecalis,the secretion of VEGF was up-regulated.In addition,the osteo/odontogenic stimulation of the EGF@Cu-BGn was evidenced with human dental pulp stem cells.The local administration of the EGF@Cu-BGn in a rat molar tooth defect infected with E.faecalis revealed significant in vivo regenerative capacity,highlighting the nanotherapeutic uses of the multifunctional nanoparticles for regenerating infected/damaged hard tissues.

Sol-gel synthesis,properties and protein loading/delivery capacity of hollow bioactive glass nanospheres with large hollow cavity and mesoporous shell

Hollow nanospheres exhibit unique properties and find a wide interest in several potential applications such as drug delivery.Herein,novel hollow bioactive glass nanospheres(HBGn)with large hollow cavity and large mesopores in their outer shells were synthesized by a simple and facile one-pot ultrasound assisted sol-gel method using PEG as the core soft-template.Interestingly,the produced HBGn exhibited large hollow cavity with ~43 nm in diameter and mesoporous shell of ~37 nm in thickness and 7 nm pore size along with nanosphere size around 117 nm.XPS confirmed the presence of Si and Ca elements at the surface of the HBGn outer shell.Notably,HBGn showed high protein loading capacity(~570 mg of Cyto c per 1 g of HBGn)in addition to controlled protein release over 5 d.HBGn also demonstrated a good in vitro capability of releasing calcium(Ca^(2+):170 ppm)and silicate(SiO_(4)^(4-):78 ppm)ions in an aqueous medium over 2 weeks under physiological-like conditions.Excellent in vitro growth of bone-like hydroxyapatite nanocrystals was exhibited by HBGn during the soaking in SBF.A possible underlying mechanism involving the formation of spherical aggregates(coils)of PEG was proposed for the formation process of HBGn.