Personalized scaffolding technologies for alveolar bone regenerative medicine

Abstract

The reconstruction of alveolar bone defects associated with teeth and dental implants remains a clinical challenge in the treatment of patients affected by disease or injury of the alveolus. The aim of this review was to provide an overview on advances made in the use of personalized scaffolding technologies coupled with biologics, cells and gene therapies that offer future clinical applications for the treatment of patients requiring periodontal and alveolar bone regeneration. Over the past decade, advancements in three-dimensional (3D) imaging acquisition technologies such as cone-beam computed tomography (CBCT) and precise scaffold fabrication methods such as 3D bioprinting have resulted in personalized scaffolding constructs based on individual patient-specific anatomical data. Furthermore, 'fiber-guiding' scaffold designs utilize topographical cues to guide ligamentous fibers to form in orientation towards the root surface to improve tooth support. Therefore, a topic-focused literature search was conducted looking into fiber-guiding and image-based scaffolds and their associated clinical applications.

Keywords: 3D printing; imaging; periodontal regeneration; scaffolds; tissue engineering.

Figure 1.. Principles and Application of Periodontal Tissue Bioengineering.

A. Components of periodontal tissue engineering. Six factors constitute for successful periodontal tissue engineering: cells, signal, scaffold, mechanical loading, pathogen control, and ideal blood supply. B. Examples of fiber guidance in periodontal tissue regeneration. On the upper left panel: SEM image of a micropatterned scaffold with grooves, a topographical cue to guide the aligned formation of new ligamentous tissue; On the upper middle panel: an illustration of PDL fiber guiding scaffold (green) and amorphous bone scaffold (blue) against the tooth surface; on the upper right panel: SEM image of seeded human PDL cells on micropatterned scaffolds (Blue arrows indicate the alignment of cells along the pillars of the scaffolds and their grooves). On the lower left panel: hematoxylin and eosin-stained (H&E) section of regenerated tissues in a rat that received a micropatterned scaffold with immobilized BMP-7 and PDGF-BB genes at a periodontal defect. The box and arrow indicate the regenerated ligamentous tissues and their oblique orientation, respectively. On the lower right panel: section of regenerated tissues in the same treatment group, stained for immunofluorescence (IF) with periostin (red), collagen III (green), and DAPI (blue). Periostin and collagen III are biomarkers for the formation of ligamentous tissue, and DAPI indicates cell nuclei. The collagen fibers are obliquely oriented and expressed throughout all the tissue due to the patterning. Adapted from Lin 2010 and Pilipchuk 2018.

Figure 2.. Image-based Scaffold design for alveolar bone bioengineering.

Step 1: Image acquisition with a cone-beam CT scan for hard tissue and intraoral scan for soft tissue; Step 2: Image pre-processing; the images from step 1 are integrated as DICOM file, then converted to STL file for preparing 3-D printable condition; Step 3: Image post-processing; 3-D volume visualization for optimization of scaffold shape; Step 4: Rapid prototyping; based on image processing, scaffolds are manufactured by the 3-D printer. Step 5: Clinical application; custom-fit scaffold is applied at the time of reconstructive surgery.

Figure 3.. Personalized scaffold technologies for periodontal engineering in furcation defects.

Personalized scaffolding process consists of 3 stages: The scaffold can be initially designed based on the tooth and bone morphology taken from a CBCT scanning before treatment. The scaffold construct then is fabricated from a balanced ratio of polymeric biomaterials such as PCL and/or PLGA using 3D printing technology. The scaffolds can be coated with genes for osteogenic factors using chemical vapor deposition (CVD) technology to allow gene vector release after cell attachment to the tissue scaffolds.