Maree Gould

The tooth is a complex biological organ composed of multiple tissues, including enamel, dentine, cementum and pulp. However, dental disease and tooth loss due to periodontitis, caries, or trauma adversely affect most adults at some time in their lives. Tooth regeneration represents a shift in the dental paradigm from removal to repair to regeneration. Tooth regeneration is an extension of the broader field of regenerative medicine, aiming to restore a tissue defect to its original form and function by using biological substitutes to replace lost teeth or tooth tissue, providing a viable alternative to currently available clinical treatments. A full array of cell sources has been trialled for endodontic regeneration, following the basic premise of tissue engineering, including cells–scaffold–bioactive molecules. Several reports have documented dental pulp-like tissue regeneration, either in vitro or following the transplantation of stem cells. Tooth regeneration follows two unique approaches: cell transplantation and cell homing. Cell transplantation has been the predominant approach, whereas cell homing aims to achieve tissue repair and regeneration of the injury site through the chemotaxis of host endogenous cells. This narrative review explores therapeutically viable tooth regeneration approaches by contrasting cell transplantation and cell-to-scaffold methodologies focussing on the cell–scaffold–bioactive molecule triad.

Bioceramic materials for endodontic treatments have gradually transformed over the years into materials with enhanced biocompatibility and chemical and mechanical properties compared to earlier generations. In endodontics procedures, these materials are used as restorative material in applications such as root-end fillings, pulp capping, perforations repair, and apexification repair procedures. However, they have far from ideal mechanical and handling properties, biocompatibility issues, aesthetic concerns due to tooth discolouration, limited antibacterial activity, and affordability, which are amongst several key limitations. Notably, bioceramic materials are popular due to their biocompatibility, sealing ability, and durability, consequently surpassing traditional materials such as gutta-percha and zinc oxide–eugenol sealers. A lack of recent advancements in the field, combined with nanomaterials, has improved the formulations of these materials to overcome these limitations. The existing literature emphasises the benefits of bioceramics while underreporting their poor mechanical properties, handling difficulties, cost, and various other drawbacks. The key gaps identified in the literature are the insufficient coverage of emerging materials, narrow scope, limited insights into future developments, and underreporting of failures and complications of the existing materials. Consequently, this review aims to highlight the key limitations of various endodontic materials, primarily focusing on calcium silicate, calcium phosphate, and bioactive glass-based materials, which are the most abundantly used materials in dentistry. Based on the literature, bioceramic materials in endodontics have significantly improved over recent years, with different combinations of materials and technology compared to earlier generations while preserving many of their original properties, with some having affordable costs. This review also identified key innovations that could shape the future of endodontic materials, highlighting the ongoing evolution and advancements in endodontic treatments.

A surgical suture is a critical medical device used to close and secure body tissues following surgery, injury, or other medical procedures, but it is often associated with the risk of surgical site infections (SSIs). To mitigate this risk, drug‐eluting sutures with antimicrobial or anti‐inflammatory properties have been developed. However, the incorporation of active pharmaceutical ingredients (APIs) frequently compromises the mechanical properties of the sutures. To address these challenges, curcumin‐loaded microspheres were first produced via the emulsion solvent evaporation method and then embedded into polymeric carriers of PCL‐PEG using a melt‐extrusion technique to achieve optimal suture diameters, thereby enhancing mechanical strength and creating an innovative drug‐delivery suture system. Notably, sutures containing Cur‐PLA‐PEG‐PCL microspheres demonstrated the highest tensile strength (170.20 ± 22.73 MPa) due to the presence of PCL. Meanwhile, sutures with Cur‐PLA‐PEG microspheres exhibited high breaking strength and stability during degradation, retaining 89.96% of their initial strength by Day 14. All suture samples also exhibited antibacterial and anti‐inflammatory activity, with a direct correlation between incubation duration and antioxidant potential. These findings suggest that the sutures hold significant potential for clinical applications in improving wound healing and reducing infections.Highlights: Curcumin‐loaded microspheres were produced via emulsion solvent evaporation and embedded into PCL‐PEG polymer carriers using melt extrusion. PLA‐PEG‐PCL sutures offer a high tensile strength of 170.20 MPa. Sutures retain 89.96% strength by Day 14, showing stability in degradation. Sustained release of curcumin from the sutures provides prolonged therapeutic effects. Sutures mitigate inflammation, reducing IL‐6 expression in keratinocytes.

Background: In normal prostate cells, receptors for oxytocin (OT), a peptide involved in regulating prostate growth are sequestered within membrane microdomains called caveolae. During cancer progression, polymerase-transcript-release factor (PTRF) is downregulated, caveolae structures are lost and receptors move onto the cell membrane. This study investigated whether proteins responsible for caveolae formation were affected by the OT peptide, also, how OT treatment affected oxytocin receptor (OTR) movement within living cells. Methods: Normal human prostate epithelial cells (PrEC) expressing caveolin and PTRF and androgen-independent (PC3) cancer cells expressing caveolin but not PTRF were used. OTR, caveolin and PTRF expression was determined in human prostate tissue. Results: PTRF expression decreased in tissue alongside an increase in malignancy. Caveolin-1 expression was downregulated by OT treatment. Caveolin-2 was decreased by OT in PrEC cells but increased in PC3 cells. PTRF was decreased by OT in PrEC. TIRF microscopy showed OTR translocated from caveolae to caveolae in normal cells, whereas OTR moved without restraint in malignant cells, possibly stimulating signaling pathways. Conclusions: This study provides evidence for the ability of OT to regulate caveolin and PTRF expression. This study elucidates possible mechanisms by which cell receptors and caveolae proteins interact to enhance cell proliferation.

As dental pulp contains the stem cells necessary for regeneration, the tooth should hold the intrinsic capacity for self-repair. A triphasic hybrid dental biocomposite (3HB) composed of biocompatible biopolymers to provide strength, antibacterial properties and protein-based cell support could provide a conducive microenvironment for the regeneration of dental structures. 3HB was incorporated into Mineral Trioxide Aggregate (ProRoot MTA) to construct a malleable injectable implant. Human tooth pulp cells (hDPCs) significantly increased proliferation in the presence of 3HB+MTA compared to 3HB or MTA alone. Cell viability decreased with MTA alone but increased with 3HB and 3HB+MTA. 3HB+MTA was implanted into the residual tooth of drilled Wistar rat M2 molars for up to 45 days. Stereological analysis from micro-CT images showed the volume of the tooth remaining. Histologically, regenerative pulpal architecture was seen invading 3HB. A continuous odontoblastic profile lined a deposit of dentin-like material suggesting reparative dentinogenesis. Overall, no infection or encapsulation was seen. Immunohistochemically, odontoblasts were seen along the margins of the wounded tooth undergoing repair. Mesenchymal cells (MSCs) were seen at the base of the drilled tooth and by 21 days had translocated into the implant itself. Cells stimulating remineralization were highly expressed in the tooth undergoing repair. CD146-positive MSCs were seen in the center of the implant, possibly stimulating remineralization. In conclusion, behavior of 3HB⁺ in vitro and in vivo provided a promising start as 3HB+MTA may serve as a viable regenerative scaffold for pulp regeneration; however, this should be further studied before clinical use can be considered.

When a tooth is diseased or damaged through caries, bioactive molecules are liberated from the pulp and dentin as part of the natural response to injury and these are key molecules for stimulating stem cell responses for tissue repair. Incorporation of these extracellular‐matrix (ECM)‐derived molecules into a hydrogel model can mimic in vivo conditions to enable dentin–pulp complex regeneration. Here, a chitosan/alginate (C/A) hydrogel is developed to sequester bovine ECM extracts. Human dental pulp cells (hDPCs) are cultured with these constructs and proliferation and cytotoxicity assays confirm that these C/A hydrogels are bioactive. Sequential z‐axis fluorescent imaging visualizes hDPCs protruding into the hydrogel as it degraded. Alizarin red S staining shows that hDPCs cultured with the hydrogels display increased calcium‐ion deposition, with dentin ECM stimulating the highest levels. Alkaline phosphatase activity is increased, as is expression of transforming growth factor‐beta as demonstrated using immunocytochemistry. Directional analysis following phase contrast kinetic image capture demonstrates that both dentin and pulp ECM molecules act as chemoattractants for hDPCs. Data from this study demonstrate that purified ECM from dental pulp and dentin when delivered in a C/A hydrogel stimulates dental tissue repair processes in vitro.

Sutures are commonly used in surgical procedures and have immense potential for direct drug delivery into the wound site. However, incorporating active pharmaceutical ingredients into the sutures has always been challenging as their mechanical strength deteriorates. This study proposes a new method to produce microspheres-embedded surgical sutures that offer adequate mechanical properties for effective wound healing applications. The study used curcumin, a bioactive compound found in turmeric, as a model drug due to its anti-inflammatory, antioxidant, and anti-bacterial properties, which make it an ideal candidate for a surgical suture drug delivery system. Curcumin-loaded microspheres were produced using the emulsion solvent evaporation method with polyvinyl alcohol (PVA) as the aqueous phase. The microspheres’ particle sizes, drug loading (DL) capacity, and encapsulation efficiency (EE) were investigated. Microspheres were melt-extruded with polycaprolactone and polyethylene glycol via a 3D bioplotter, followed by a drawing process to optimise the mechanical strength. The sutures’ thermal, physiochemical, and mechanical properties were investigated, and the drug delivery and biocompatibility were evaluated. The results showed that increasing the aqueous phase concentration resulted in smaller particle sizes and improved DL capacity and EE. However, if PVA was used at 3% w/v or below, it prevented aggregate formation after lyophilisation, and the average particle size was found to be 34.32 ± 12.82 μm. The sutures produced with the addition of microspheres had a diameter of 0.38 ± 0.02 mm, a smooth surface, minimal tissue drag, and proper tensile strength. Furthermore, due to the encapsulated drug-polymer structure, the sutures exhibited a prolonged and sustained drug release of up to 14 d. Microsphere-loaded sutures demonstrated non-toxicity and accelerated wound healing in the in vitro studies. We anticipate that the microsphere-loaded sutures will serve as an excellent biomedical device for facilitating wound healing.

Montmorillonite (MMT) is a biocompatible, cost-effective phyllosilicate mineral clay material with a nanolayered structure belonging to the smectite group. MMT is frequently used as an adsorbent catalyst in organic synthesis, food additives, cosmetics, medical applications and many other applications in varying industries. MMT has been incorporated into numerous experimental dental restorative materials as a reinforcing filler due to its high aspect ratio, forming interfacial solid bonds with the polymer matrix. The relatively high cation exchange capacity and layered structure of MMT pave the way as a medium for drug delivery systems. Furthermore, the incorporation of ions such as calcium, fluoride, silver, and zinc potentially increase the remineralization properties and antibacterial properties of MMT-based dental materials. Despite modern dental restorative materials having advanced significantly with innovations in material nanoscience, challenges such as biocompatibility, inadequate mechanical properties, marginal leakage, polymerization shrinkage, aesthetic concerns, and overall costs remain to be addressed. This review investigates the potential of montmorillonite (MMT) in dentistry, emphasizing its distinctive properties, composite formulations, and applications. It assesses the current state of research in these areas, aiming to highlight existing gaps in knowledge, emerging trends, and lesser-known applications of MMT-based materials. The review underscores MMT’s promise as an alternative material across various dental applications while noting the scarcity of research on completed products and in vivo clinical studies.

Hydroxyapatite is widely used in bone implantation because of its similar mineral composition to natural bone, allowing it to serve as a biocompatible osteoconductive support. A bovine-derived hydroxyapatite (BHA) scaffold was developed through an array of defatting and deproteinization procedures. The BHA scaffold was substituted with fluoride ions using a modified sol-gel method to produce a bovine-derived fluorapatite (BFA) scaffold. Fourier-transform infrared spectroscopy and X-ray diffraction analysis showed that fluoride ions were successfully substituted into the BHA lattice. According to energy dispersive X-ray analysis, the main inorganic phases contained calcium and phosphorus with a fluoride ratio of ~1–2 wt%. Scanning electron microscopy presented a natural microporous architecture for the BFA scaffold with pore sizes ranging from ~200–600 μm. The BHA scaffold was chemically stable and showed sustained degradation in simulated-body fluid. Young’s modulus and yield strength were superior in the BFA scaffold to BHA. In vitro cell culture studies showed that the BFA was biocompatible, supporting the proliferative growth of Saos-2 osteoblast cells and exhibiting osteoinductive features. This unique technique of producing hydroxyapatite from bovine bone with the intent of producing high performance biomedically targeted materials could be used to improve bone repair.

In the event of excessive damage to bone tissue, the self-healing process alone is not sufficient to restore bone integrity. Three-dimensional (3D) printing, as an advanced additive manufacturing technology, can create implantable bone scaffolds with accurate geometry and internal architecture, facilitating bone regeneration. This study aims to develop and optimise hydroxyapatite-polyethylene glycol diacrylate (HA-PEGDA) hydrogel inks for extrusion 3D printing of bone tissue scaffolds. Different concentrations of HA were mixed with PEGDA, and further incorporated with pluronic F127 (PF127) as a sacrificial carrier. PF127 provided good distribution of HA nanoparticle within the scaffolds and improved the rheological requirements of HA-PEGDA inks for extrusion 3D printing without significant reduction in the HA content after its removal. Higher printing pressures and printing rates were needed to generate the same strand diameter when using a higher HA content compared to a lower HA content. Scaffolds with excellent shape fidelity up to 75-layers and high resolution (∼200 µm) with uniform strands were fabricated. Increasing the HA content enhanced the compression strength and decreased the swelling degree and degradation rate of 3D printed HA-PEGDA scaffolds. In addition, the incorporation of HA improved the adhesion and proliferation of human bone mesenchymal stem cells (hBMSCs) onto the scaffolds. 3D printed scaffolds with 2 wt% HA promoted osteogenic differentiation of hBMSCs as confirmed by the expression of alkaline phosphatase activity and calcium deposition. Altogether, the developed HA-PEGDA hydrogel ink has promising potential as a scaffold material for bone tissue regeneration, with excellent shape fidelity and the ability to promote osteogenic differentiation of hBMSCs.