Bioprinting-Based PDLSC-ECM Screening for in Vivo Repair of Alveolar Bone Defect Using Cell-Laden, Injectable and Photocrosslinkable Hydrogels

Abstract

Periodontitis is an inflammatory disease worldwide that may result in periodontal defect (especially alveolar bone defect) and even tooth loss. Stem-cell-based approach combined with injectable hydrogels has been proposed as a promising strategy in periodontal treatments. Stem cells fate closely depends on their extracellular matrix (ECM) characteristics. Hence, it is necessary to engineer an appropriate injectable hydrogel to deliver stem cells into the defect while serving as the ECM during healing. Therefore, stem cell-ECM interaction should be studied for better stem cell transplantation. In this study, we developed a bioprinting-based strategy to study stem cell–ECM interaction and thus screen an appropriate ECM for in vivo repair of alveolar bone defect. Periodontal ligament stem cells (PDLSCs) were encapsulated in injectable, photocrosslinkable composite hydrogels composed of gelatin methacrylate (GelMA) and poly­(ethylene glycol) dimethacrylate (PEGDA). PDLSC-laden GelMA/PEGDA hydrogels with varying composition were efficiently fabricated via a 3D bioprinting platform by controlling the volume ratio of GelMA-to-PEGDA. PDLSC behavior and fate were found to be closely related to the engineered ECM composition. The 4/1 GelMA/PEGDA composite hydrogel was selected since the best performance in osteogenic differentiation in vitro. Finally, in vivo study indicated a maximal and robust new bone formation in the defects treated with the PDLSC-laden hydrogel with optimized composition as compared to the hydrogel alone and the saline ones. The developed approach would be useful for studying cell–ECM interaction in 3D and paving the way for regeneration of functional tissue.

Recent Advances in Photo-Crosslinkable Hydrogels for Biomedical Applications

“…The degradation rate of PEGDA hydrogel can be improved by combining it with other enzymatically or hydrolytically degradable materials [32]. For instance, degradation of PEGDA was increased up to 80 after 14days of immersion in collagenase solution in which GelMA was added to form PEGDA/GelMA hybrid hydrogel for tooth tissue engineering [31]. …”

“…Due to this, it allows growth of cancer cells and formation of tumorspheres, indicating its great potential in developing various types of 3D in vitro cancer model, such as a breast cancer model, gastrointestinal cancer model and bone cancer model [44]. However, in order to utilize it as a 3D cell culture platform for developing tissue-engineered constructs or implants, it has to be combined with other biomaterials possessing cell adhesive properties, such as HA, GelMA, collagen and polyaniline [31,32,41,48]. PEGDA/GelMA hybrid hydrogel and PEGDA/collagen hybrid hydrogel were loaded with adult stem cells, respectively, for tooth and vascular regeneration [31,32].…”

“…However, in order to utilize it as a 3D cell culture platform for developing tissue-engineered constructs or implants, it has to be combined with other biomaterials possessing cell adhesive properties, such as HA, GelMA, collagen and polyaniline [31,32,41,48]. PEGDA/GelMA hybrid hydrogel and PEGDA/collagen hybrid hydrogel were loaded with adult stem cells, respectively, for tooth and vascular regeneration [31,32]. PEGDA/HA hybrid hydrogel was employed to promote bone regeneration, which can be functionalized with laponite XLG nanoclay (a composite that releases bioactive ions Mg 2+ and Si 4+ ) to create a favorable microenvironment for in vivo osteogenesis [41] (Figure 2B).…”

Polyamide/PEG Blends as Biocompatible Biomaterials for the Convenient Regulation of Cell Adhesion and Growth

“…For the application of synthetic polymers as biomaterials, their hydrophilization by conjugation or blending with polyethylene glycol (PEG) (PEGylation) or the conjugation to functional biomolecules (bioconjugation) are very important strategies . Furthermore, blending with some natural polymers or with naturally derived polymers (e.g., celluloses) is also a very important concept . Encapsulation of stem cells in hydrogels composed of gelatin methacrylate and poly(ethylene glycol) dimethylacrylate and printing has high potential for functional tissue regeneration.…”

Natural History Collections as Inspiration for Technology

“…The biomimetic sciences have proceeded to work on problems in many areas of the clinic, in regenerative medicine, tissue engineering, healthcare materials (e.g., antibacterial films) and drug delivery . Various plants and animals teach us about many different physical and mechanical lessons for design and function, mainly when making new materials and structures.…”