Multicompartmental Scaffolds for Coordinated Periodontal Tissue Engineering

Successful periodontal repair and regeneration requires the coordinated responses from soft and hard tissues as well as the soft tissue-to-bone interfaces. Inspired by the hierarchical structure of native periodontal tissues, tissue engineering technology provides unique opportunities to coordinate multiple cell types into scaffolds that mimic the natural periodontal structure <i>in vitro</i>. In this study, we designed and fabricated highly-ordered multicompartmental scaffolds by melt electrowriting, an advanced 3D printing technique. This strategy attempted to mimic the characteristic periodontal microenvironment through multicompartmental constructs comprised of 3 tissue-specific regions: (i) a bone compartment with dense mesh structure; (ii) a ligament compartment mimicking the highly-aligned periodontal ligaments (PDL); and (iii) a transition region that bridges the bone and ligament, a critical feature that differentiates this system from mono- or bi- compartmental alternatives. The multicompartmental constructs successfully achieved coordinated proliferation and differentiation of multiple cell types <i>in vitro </i>within short time, including both ligamentous- and bone-derived cells. Long-term 3D co-culture of primary human osteoblasts and PDL fibroblasts led to a mineral gradient from calcified to uncalcified regions with PDL-like insertions within the transition region, an effect that is challenging to achieve with mono- or bi- compartmental platforms. This process effectively recapitulates the key feature of interfacial tissues in periodontium. Collectively, this tissue engineered approach offers a fundament for engineering periodontal tissue constructs with characteristic 3D microenvironments similar to native tissues. This multicompartmental 3D printing approach is also highly compatible with the design of next-generation scaffolds, with both highly adjustable compartmentalization properties and patient-specific shapes, for multi-tissue engineering in complex periodontal defects.