Hybrid Biopolymer/bioceramic 3d-printed Scaffolds Embedded With Doxorubicin Nanoparticulate Systems For Local Treatment Of Osteosarcoma

• By: DAIHOM, Baher (The American University of Iraq - Baghdad, Iraq)
• Co-author(s): Dr Baher Daihom (AUIB, Baghdad, Iraq / Cairo university, Cairo, Egypt / University of Texas, Austin, USA)
  Amit Pillai (University of Texas, Austin, USA)
  Jaidev Chakka (University of Texas, Austin, USA)
  Niloofar Heshmati (University of Texas, Austin, USA)
  Santosh Bashyal (University of Texas, Austin, USA)
  Dr Mohammed Maniruzzaman (University of Texas, Austin, USA)
  
• Abstract:

  Introduction: Osteosarcoma continues to present a significant challenge in oncology, owing to its prevalence and the deleterious side effects associated with current treatment modalities. Consequently, there is a critical demand for novel methods. This research contributes to the advancement of the field by investigating the combination of Doxorubicin-loaded nanoparticles with cutting-edge 3D printing technology, to fabricate scaffolds tailored for localised tumour treatment and bone regeneration.
  
  Methods: The study rigorously assessed four nanoparticulate systems' effectiveness in the treatment of osteosarcoma: liposomes, albumin nanoparticles, spanlastics, and chitosan-coated spanlastics, each imbued with Doxorubicin. In recognition of the necessity to attenuate the toxicity profile of Doxorubicin, these nanoparticulate systems were developed and integrated into hybrid 3D-printed scaffolds comprising a 3% alginate and 9% methylcellulose hydrogel, impregnated with nanocarriers and calcium phosphate cement. An exhaustive array of tests was executed, encompassing the characterisation of particle size, zeta potential, and drug release kinetics. The in vitro analyses included fluorescence imaging for cellular uptake, cytotoxicity against the human osteosarcoma cell lines MG-63, and cell proliferation with human mesenchymal stem cells. Additionally, RT-PCR was utilised to analyse four genes implicated in osteosarcoma within the cells.
  
  Results: A key finding of the study was the exceptional efficacy of the spanlastics and chitosan-coated spanlastics, which demonstrated marked advancements in drug delivery and therapeutic outcomes. Spanlastics, with their innovative elastic vesicular construction, facilitated sustained Doxorubicin release, significantly enhancing bioavailability. The chitosan-coated spanlastics were particularly distinguished by an 85% Doxorubicin encapsulation efficiency and a prolonged release profile, which contributed to a 60% reduction in MG-63 cell viability when contrasted with the control group. The chitosan coating also augmented cellular uptake and the localised delivery of the therapeutic agent. The structural soundness and optimised porosity of the 3D scaffolds were vital in providing the necessary infrastructure for bone regeneration, as evidenced by the proliferation of osteoblastic cells on the scaffold's surface and the support for the attachment of human mesenchymal stem cells to its calcium phosphate elements.
  
  Conclusion: The research establishes the significant effectiveness of Doxorubicin-laden chitosan-coated spanlastics within bespoke 3D-printed scaffolds as a transformative method for the localised treatment of osteosarcoma. The dual-function scaffold not only delivers potent cytotoxicity against osteosarcoma cells but also fosters an environment conducive to the regrowth of bone tissue. The confluence of sophisticated nanoparticle engineering with precision 3D printing technology presents a formidable platform for the development of patient-specific, targeted treatments. This cross-disciplinary breakthrough heralds new pathways in personalised medicine and represents a significant advance in the clinical handling of osteosarcoma, with the potential to markedly enhance patient prognoses and quality of life following therapy.