Abstract: Advanced therapy medicinal products are biological products that require rigorous long-term monitoring of safety and efficacy due to their sustained effects. The development of tissue-engineered products demands careful consideration of tissue-specific properties, surgical requirements, biomaterial compatibility, host tissue integration, and potential immune responses. In this study, we developed and evaluated the safety and efficacy of 3D-bioprinted constructs containing cells for bone regeneration in preclinical models. Three types of human mesenchymal stem cells (bone marrow-derived, adipose-derived, and nasal turbinate-derived) were combined with varying concentrations of collagen and polycaprolactone. Safety assessments included comprehensive tumorigenicity evaluations involving cell viability assays, protein quantification, and whole-genome sequencing under multiple conditions to confirm genetic stability and mitigate tumorigenic risks. Short-term toxicity was evaluated by subcutaneous implantation in nude mice, with blood and serum analyses confirming the absence of acute toxicity or histological abnormalities in major organs. Efficacy studies in rabbits exhibited safety through posttransplantation analyses, with 6-month tissue analyses showing significantly elevated expression of osteopontin and runt-related transcription factor 2 (RUNX2) proteins in constructs containing human nasal turbinate-derived mesenchymal stem cells, indicating successful tissue integration and bone-specific marker expression. Long-term follow-up confirmed construct integrity and sustained bone formation. These findings highlight the importance of comprehensive safety and efficacy evaluations across cell types and construct compositions in the development of 3D-bioprinted constructs for bone regeneration. This study establishes a systematic framework for material selection and validation in preclinical stages, providing a foundation for future clinical applications in regenerative medicine and tissue engineering.The alternative text for this image may have been generated using AI.

Comparative analysis of the safety and efficacy of 3D-bioprinted constructs embedded with human mesenchymal stem cells for bone regeneration

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