Hard tissue repair and regeneration cost hundreds of billions of dollars annually worldwide, and the need has substantially increased as the population has aged. Hard tissues include bone and tooth structures that contain calcium phosphate minerals. Smart biomaterial-based tissue engineering and regenerative medicine methods have the exciting potential to meet this urgent need. Smart biomaterials and constructs refer to biomaterials and constructs that possess instructive/inductive or triggering/stimulating effects on cells and tissues by engineering the material’s responsiveness to internal or external stimuli or have intelligently tailored properties and functions that can promote tissue repair and regeneration. The smart material-based approaches include smart scaffolds and stem cell constructs for bone tissue engineering; smart drug delivery systems to enhance bone regeneration; smart dental resins that respond to pH to protect tooth structures; smart pH-sensitive dental materials to selectively inhibit acid-producing bacteria; smart polymers to modulate biofilm species away from a pathogenic composition and shift towards a healthy composition; and smart materials to suppress biofilms and avoid drug resistance. These smart biomaterials can not only deliver and guide stem cells to improve tissue regeneration and deliver drugs and bioactive agents with spatially and temporarily controlled releases but can also modulate/suppress biofilms and combat infections in wound sites. The new generation of smart biomaterials provides exciting potential and is a promising opportunity to substantially enhance hard tissue engineering and regenerative medicine efficacy.

Human induced pluripotent stem cells (hiPSCs) are an exciting cell source with great potential for tissue engineering. Human bone marrow mesenchymal stem cells (hBMSCs) have been used in clinics but are limited by several disadvantages, hence alternative sources of MSCs such as umbilical cord MSCs (hUCMSCs) are being investigated. However, there has been no report comparing hiPSCs, hUCMSCs and hBMSCs for bone regeneration. The objectives of this pilot study were to investigate hiPSCs, hUCMSCs and hBMSCs for bone tissue engineering, and compare their bone regeneration via seeding on biofunctionalized macroporous calcium phosphate cement (CPC) in rat cranial defects. For all three types of cells, approximately 90% of the cells remained alive on CPC scaffolds. Osteogenic genes were up-regulated, and mineral synthesis by cells increased with time in vitro for all three types of cells. The new bone area fractions at 12 weeks (mean ± sd; n = 6) were (30.4 ± 5.8)%, (27.4 ± 9.7)% and (22.6 ± 4.7)% in hiPSC-MSC-CPC, hUCMSC-CPC and hBMSC-CPC respectively, compared to (11.0 ± 6.3)% for control (p < 0.05). No significant differences were detected among the three types of stem cells (p > 0.1). New blood vessel density was higher in cell-seeded groups than control (p < 0.05). De novo bone formation and participation by implanted cells was confirmed via immunohistochemical staining. In conclusion, (1) hiPSCs, hUCMSCs and hBMSCs greatly enhanced bone regeneration, more than doubling the new bone amount of cell-free CPC control; (2) hiPSC-MSCs and hUCMSCs represented viable alternatives to hBMSCs; (3) biofunctionalized macroporous CPC-stem cell constructs had a robust capacity for bone regeneration.

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Objectives The objectives of this study were to 1) demonstrate X-ray microcomputed tomography (μCT) as a viable method for determining the polymerization shrinkage and microleakage on the same sample accurately and non-destructively, and 2) investigate the effect of sample geometry (e.g., C-factor and volume) on polymerization shrinkage and microleakage. Methods Composites placed in a series of model cavities of controlled C-factors and volumes were imaged using μCT to determine their precise location and volume before and after photopolymerization. Shrinkage was calculated by comparing the volume of composites before and after polymerization and leakage was predicted based on gap formation between composites and cavity walls as a function of position. Dye penetration experiments were used to validate μCT results. Results The degree of conversion (DC) of composites measured using FTIR in reflectance mode was nearly identical for composites filled in all model cavity geometries. The shrinkage of composites calculated based on μCT results was statically identical regardless of sample geometry. Microleakage, on the other hand, was highly dependent on the C-factor as well as the composite volume, with higher C-factors and larger volumes leading to a greater probability of microleakage. Spatial distribution of microleakage determined by μCT agreed well with results determined by dye penetration. Significance μ CT has proven to be a powerful technique in quantifying polymerization shrinkage and corresponding microleakage for clinically relevant cavity geometries.

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The purpose of this project is to design and develop a clinically applicable self-healing dental composite (SHDC). The value of resin-based dental restorations could be improved by increasing their service lives. One way to improve longevity is to obturate micro-cracks that form during or after the composite hardens in the dental cavity. Toward this end, we introduce here a new type of SHDC made with contemporary dental components plus two additional ingredients: a healing powder (HP, strongtium fluoroaluminosilicate particles) and a healing liquid (HL, aqueous solutions of polyacrylic acids) that is enclosed within silica microcapsules. As micro-cracks develop, they will break the microcapsules in their propagation path, thereby releasing HL. This liquid will then react with particles of HP exposed by the crack formation, forming an insoluble reaction product that fills and seals the cracks. The key factors to achieve this self-healing of cracks are discussed. The elastic modulus of a SHDC appeared to be satisfactory. The healing process was confirmed by means of mechanical, morphological, and chemical methods. The SHDC restored micro-cracks without external intervention, thereby showing potential for increasing the service lives of dental restorations. Importantly, this SHDC contains only clinically-tested, biocompatible materials, making it readily applicable.

The short average service life of traditional dental composite restorative materials and increasing occurrence of secondary caries adjacent to composite restorations and sealants are necessitating the development of new, longer lasting compositions. Novel monomers and their polymers, reinforcing fillers, and adhesive components are needed. The goal of this research is to develop resin systems for use in restorations, sealants, and other dental services that are superior in properties and endurance to currently used bisphenol A glycidyl dimethacrylate/triethylene glycol dimethacrylate (Bis-GMA/TEGDMA) and urethane–dimethacrylate products. Ether-based monomers and their polymers that were not susceptible to enzymatic or hydrolytic degradation were prepared and characterized. They showed no degradation under hydrolytic and enzymatic challenges, whereas the hydrolysis of ester links weakened contemporary resins within 16 days under these challenges. The success of the ether-based materials is promising in making durable systems that are subjected to long-term biochemical and hydrolytic challenges in oral environments.