Clinical translation of polycaprolactone-based tissue engineering scaffolds, fabricated via additive manufacturing: A review of their craniofacial applications

The craniofacial region is characterized by its intricate bony anatomy and exposure to heightened functional forces presenting a unique challenge for reconstruction. Additive manufacturing has revolutionized the creation of customized scaffolds with interconnected pores and biomimetic microarchitecture, offering precise adaptation to various craniofacial defects. Within this domain, medical-grade poly( epsilon-caprolactone) (PCL) has been extensively used for the fabrication of 3D printed scaffolds, specifically tailored for bone regeneration. Its adoption for load-bearing applications was driven mainly by its mechanical properties, adjustable biodegradation rates, and high biocompatibility. The present review aims to consolidating current insights into the clinical translation of PCL-based constructs designed for bone regeneration. It encompasses recent advances in enhancing the mechanical properties and augmenting biodegradation rates of PCL and PCL-based composite scaffolds. Moreover, it delves into various strategies improving cell proliferation and the osteogenic potential of PCL-based materials. These strategies provide insight into the refinement of scaffold microarchitecture, composition, and surface treatments or coatings, that include certain bioactive molecules such as growth factors, proteins, and ceramic nanoparticles. The review critically examines published data on the clinical applications of PCL scaffolds in both extraoral and intraoral craniofacial reconstructions. These applications include cranioplasty, nasal and orbital floor reconstruction, maxillofacial reconstruction, and intraoral bone regeneration. Patient demographics, surgical procedures, follow-up periods, complications and failures are thoroughly discussed. Although results from extraoral applications in the craniofacial region are encouraging, intraoral applications present a high frequency of complications and related failures. Moving forward, future studies should prioritize refining the clinical performance, particularly in the domain of intraoral applications, and providing comprehensive data on the longterm outcomes of PCL-based scaffolds in bone regeneration. Future perspective and limitations regarding the transition of such constructs from bench to bedside are also discussed.