3D Additive Manufactured Composite Scaffolds with Antibiotic-loaded Lamellar Fillers for Bone Infection Prevention and Tissue Regeneration

Abstract

Bone infections following open bone fracture or implant surgery remain a challenge in the orthopedics field. In order to avoid high doses of systemic drug administration, optimized local antibiotic release from scaffolds is required. 3D additive manufactured (AM) scaffolds made with biodegradable polymers are ideal to support bone healing in non-union scenarios and can be given antimicrobial properties by the incorporation of antibiotics. In this study, ciprofloxacin and gentamicin intercalated in the interlamellar spaces of magnesium aluminum layered double hydroxides (MgAl) and α-zirconium phosphates (ZrP), respectively, are dispersed within a thermoplastic polymer by melt compounding and subsequently processed via high temperature melt extrusion AM (~190 °C) into 3D scaffolds. The inorganic fillers enable a sustained antibiotics release through the polymer matrix, controlled by antibiotics counterions exchange or pH conditions. Importantly, both antibiotics retain their functionality after the manufacturing process at high temperatures, as verified by their activity against both Gram + and Gram -bacterial strains. Moreover, scaffolds loaded with filler-antibiotic do not impair human mesenchymal stromal cells osteogenic differentiation, allowing matrix mineralization and the expression of relevant osteogenic markers.Overall, these results suggest the possibility of fabricating dual functionality 3D scaffolds via high temperature melt extrusion for bone regeneration and infection prevention.

Chloroplast‐inspired Scaffold for Infected Bone Defect Therapy: Towards Stable Photothermal Properties and Self‐Defensive Functionality

“…Bacterial infections arising from orthopedic surgery or osteomyelitis remain a difficult clinical problem. [ 3 ] Therefore, the bacterial inhibition ratio of CS/PCL/BP/PDA@Ag scaffolds against E. coli and S. aureus was investigated first in vitro. As shown in Figure a, the antibacterial activity of the CS/PCL/BP/PDA@Ag scaffolds was positively correlated with the initial concentration of AgNO 3 .…”

“…Implant‐associated infections remain a serious problem in bone defect therapy and frequently result in repair failure, potentially threatening the health of patients. [ 1,2 ] Recently, implanted scaffolds loaded with various antibiotics, [ 3,4 ] such as ciprofloxacin and gentamicin, or antimicrobial nanoparticles, [ 5 ] such as gold and silver, have gradually become a research hotspot. Nevertheless, antibiotic resistance, disquieting cytotoxicity of over‐released nanoparticles, and weak osteo‐integration and osteo‐inductivity of the scaffold are still limitations of these implantations.…”

Layered double hydroxide-based nanomaterials for biomedical applications

“…In order to further improve the bioavailability of LDH-based tissue engineering materials, it is necessary to introduce drugs (e.g., analgesic, anti-inflammatory, anti-bone resorption drugs), growth factors, or antimicrobial agents for enhancing the clinical effect. [449][450][451][452][453] Alendronate (AL), an anti-osteoporosis drug, can prevent osteoclast-mediated bone resorption and therefore helps to maintain the microstructure of bone tissue. However, large doses are required for the desired therapeutic effect, which unfortunately also causes significant side effects.…”

Shaping and properties of thermoplastic scaffolds in tissue regeneration: The effect of thermal history on polymer crystallization, surface characteristics and cell fate

“…This method could provide a potential simpler approach to induce stem cell differentiation towards the osteogenic lineage compared to the more conventional approaches of creating polymer composite scaffolds [74], despite the use of specific inorganic fillers could still be combined with the control in surface roughness and crystallinity here proposed to further provide the fabricated scaffolds with other biofunctional properties. Examples of further instructive AM scaffolds include bioglasses to stimulate angiogenesis in combination with osteogenesis [75], and antibiotics to prevent possible risks of infections [76], among others.…”