Hard Tissue Regeneration Research Articles

Formation of bone tissue apatite on starch-based nanofiber-capped nanohydroxyapatite and reduced graphene oxide: a preliminary study.

In the present study, blends of polyvinyl alcohol (PVA), starch (SH), nanohydroxyapatite (Nano-HA), and reduced graphene oxide (r-GO) were used to fabricate an electrospun nano scaffold (ENS), via electrospinning for their potential application in oral and maxillofacial bone soft and hard tissue regeneration. The scaffold was characterized for its physicochemical and mechanical properties. An invitro study was carried out using human osteoblast MG-63 bone cells. Surface characterization, particularly the analysis of calcium content, was performed before and after immersion in the simulated body fluid (SBF). Additionally, the impact of surface treatment on antimicrobial activity was investigated. The results demonstrated that the tensile strength (18.12 ± 0.14MPa), elongation at break (19.23 ± 0.11%), and flexing index (20.15 ± 0.13%) of the ENS were outstanding, indicating promising performance. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays demonstrated the biocompatible nature of the ENS. The bioactivity test result of ENS showed excellent deposition of bone apatite crystals. The ENS exhibited antimicrobial properties against E. coli (3.41 ± 0.03mm) and S. aureus (3.12 ± 0.08mm). The ENS, possessing the desired properties, has the potential to be tested in large animals for oral and maxillofacial bone and soft tissue regeneration after obtaining the necessary approvals. The developed ENS offers a promising solution for bone tissue regeneration in the oral and maxillofacial region.

Heterotopically differentiated PDLSCs-laden 3D bioprinting scaffolds for concurrent oral hard and soft tissue regeneration

Following dental extraction, the alveolar bone and gingival tissues could undergo varying degrees of resorption, affecting subsequent implant integration and aesthetic outcomes. Adequate volume of both hard and soft tissues is essential for optimal results. Three-dimensional (3D) bioprinting technology offers the advantages of biomimicry, personalization, and precise spatial distribution, which are pivotal for enhancing the success and esthetics of dental restorations. In this study, we fabricated a construct with a natural transition and varying material concentrations by 3D bioprinting, comprising an upper layer of Collagen/Alginate/periodontal ligament stem cells (PDLSCs) and a lower layer of Collagen/nano-hydroxyapatite (nHA)/Alginate/PDLSCs. Characterization of the physicochemical properties revealed that the incorporation of nHA significantly enhanced the mechanical properties of both the bioink and the construct. Flow cytometry analysis confirmed the stemness of PDLSCs. Scanning electron microscopy (SEM) revealed that the construct possesses satisfactory pore density and a natural transition at the stratification point. The construct displayed good cell viability and proliferation, with the cellular movement observed at the stratification interface after bioprinting. Differentiation staining and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) results demonstrated that PDLSCs within the 3D construct are capable of both osteogenic and fibroblastic differentiations. Ectopic transplantation in mice confirmed the biocompatibility of the construct. A rat tooth extraction model validated the construct's effectiveness in the integrated regeneration of both hard and soft tissues in alveolar ridge preservation (ARP). In conclusion, this personalized, concentration-varied 3D construct exhibits excellent biocompatibility and tissue preservation effects, holding significant potential for clinical application.  

Comparative Study of Photobiomodulation Effects on Alveolar Socket Hard Tissue Healing in Rats: Application of 980 nm Versus 810 nm Lasers.

Background: This study aimed to explore the differential effects of photobiomodulation (PBM) via 980 nm and 810 nm lasers on the hard tissue healing of rat alveolar sockets, with a focus on a comparative analysis of hard tissue regeneration and osteogenic gene expression. Objective: This study aimed to explore the effects of PBM using 980 nm and 810 nm lasers on hard tissue healing of rat alveolar sockets, focusing on hard tissue regeneration and osteogenic gene expression. Materials and Methods: Thirty-six male Wistar rats (5 weeks old) had both right and left maxillary first molars extracted. Post extraction, the right alveolar sockets received PBM treatment with either 980 nm (0.3 W, 18 J/cm2) or 810 nm (0.1 W, 6 J/cm2) lasers for seven days, whereas the left sockets served as controls. Rats were euthanized on days 3, 7, 14, and 28 for histopathological, immunohistochemical, micro computed tomography (micro-CT), and quantitative polymerase chain reactionanalyses. Results: On day 3, early granulation tissue, neovascularization, and inflammatory cell aggregates were observed in all groups. By day 7, active osteoclasts and osteoblasts were noted, with a significant increase in CD31-positive cells in the 980 nm group (p < 0.05). Day 14 showed new bone formation, and by day 28, increased cancellous bone and collagen content were present in all groups, with no significant differences between them (p > 0.05). Gene expression analysis revealed higher BMP-2 and Runx-2 levels in laser-treated groups on day 14 (p < 0.05), with the 980 nm group having higher BMP-2 levels than the 810 nm group (p < 0.05). Bone sialoprotein expression was higher in laser-treated groups on days 14 and 28 (p < 0.05), and osteocalcin expression was highest in the 980 nm group on both days (p < 0.05). Micro-CT analysis showed no significant differences among groups in bone mineral density, bone surface (BS)/bone volume (BV), or bone volume (BV)/TV (total volume) indices. Conclusion: PBM with 980 nm and 810 nm lasers promotes early-stage hard tissue healing in extraction sockets, with the 980 nm laser more effectively enhancing osteogenic gene expression, suggesting its potential as an adjunctive therapy in dental and oral surgery.

Mechanistic Insights of Amino Acid Binding to Hydroxyapatite: Molecular Dynamics Charts Future Directions in Biomaterial Design.

Extensive efforts have been made to improve the understanding of hard tissue regeneration, essential for advancing medical applications like bone graft materials. However, the mechanisms of bone biomineralization, particularly the regulation of hydroxyapatite growth by proteins/peptides, remain debated. Small biomolecules such as amino acids are ideal for studying these mechanisms due to their simplicity and relevance as protein/peptide building blocks. This study investigates the binding affinity of four amino acids including glycine (Gly), proline (Pro), lysine (Lys), and aspartic acid (Asp) to the hydroxyapatite (HAP) (100) surface through molecular dynamics simulations. Our findings reveal that aspartic acid exhibits the most energetically favorable binding affinity, attributed to its additional carboxylate group (-COO-), which facilitates stronger interactions with Ca2+ ions on the HAP surface compared to other amino acids with single carboxylate groups. This highlights the critical role of specific functional groups in modulating binding strength, emphasizing that the presence of multiple binding sites in amino acids enhances binding stability. Interestingly, the study also uncovers the significance of water-mediated interactions, as the compact water layer above the HAP surface acts as a barrier, complicating direct binding and underscoring the need to consider solvation effects in simulations. Glycine, due to its small size, demonstrates a unique ability to penetrate this tightly bound water monolayer, suggesting that molecular size influences binding dynamics. These simulations offer detailed insights into the atomic-level interactions, providing a deeper understanding of binding affinity and stability. These insights are pertinent for designing peptides or proteins with enhanced interactions with biomaterials, particularly in mimicking natural bone-binding processes.

Integrating Phosphate Enhances Biomineralization Effect of Methacrylate Cement in Vital Pulp Treatment with Improved Human Dental Pulp Stem Cells Stimulation.

Vital pulp treatment (VPT) is crucial for preserving the health and function of the tooth in cases where the pulp tissue remains vital despite exposure. Various materials are introduced for this purpose. However, challenges such as low strength, high solubility, and tooth discoloration persist. Methylmethacrylate-based cement (MC) offers excellent sealing ability, feasibility, and mechanical properties, making it a promising alternative for VPT. Phosphate-based glass (PBG) has the potential to promote hard tissue regeneration by releasing key inducers, phosphorus (P) and calcium (Ca), for reparative odontogenesis. This study investigates PBG-integrated MC (PIMC) by characterizing its properties, assessing human dental pulp stem cell activity related to initial inflammatory adaptation and odontogenic differentiation, and evaluating hard tissue formation using an in vivo dog pulpotomy model. Results indicate that a 5% PBG-integrated MC (5PIMC) maintains the physicochemical properties of MC. Furthermore, 5PIMC demonstrates cytocompatibility, excellent expression of osteo/odontogenic markers, and resistance to inflammatory markers, significantly outperforming MC. Enhanced hard tissue formation is observed in the dental pulp of mongrel dog teeth treated with 5PIMC. These findings suggest that 5PIMC could be an optimal and suitable material for reparative odontogenesis through VPT.

Healing sequelae following tooth extraction and dental implant placement in an aged, ovariectomy model.

At present, a lack of consensus exists regarding the clinical impact of osteoporosis on alveolar bone metabolism during implant osseointegration. While limited preclinical and clinical evidence demonstrates a negative influence of osteoporosis on dental extraction socket healing, no preclinical studies offer data on the results of implant placement in 6-mo-old, ovariectomized (OVX) Sprague-Dawley rats. This study aimed to investigate the outcomes of dental tooth extraction socket healing and implant placement in a rodent model of osteoporosis following daily vehicle (VEH) or abaloparatide (ABL) administration. Micro-CT and histologic analysis demonstrated signs of delayed wound healing, consistent with alveolar osteitis in extraction sockets following 42d of healing in both the VEH and ABL groups. In a semiquantitative histological analysis, the OVX-ABL group demonstrated a tendency for improved socket regeneration with a 3-fold greater rate for moderate socket healing when compared to the OVX-VEH group (43% vs 14%), however, this finding was not statistically significant (p=.11). No significant differences were observed between vehicle and test groups in terms of implant outcomes (BMD and bone volume/total volume) at 14- and 21-d post-implant placement. Abaloparatide (ABL) significantly increased BMD of the femoral shaft and intact maxillary alveolar bone sites in OVX animals, demonstrating the therapeutic potential for oral hard tissue regeneration. The present model involving estrogen-deficiency-induced bone loss demonstrated an impaired healing response to dental extraction and implant installation.

Atomic scale investigation and cytocompatibility of copper and zinc-loaded phosphate-based glasses prepared by coacervation

Phosphate-based glasses (PBGs) are bioresorbable materials that find application in the field of controlled drug delivery and tissue engineering. The structural arrangements of the phosphate units in PBGs, along with the knowledge of how therapeutic metallic ions are embedded in the phosphate network are important in understanding the degradation and targeted release properties of these materials. Using a combination of Raman spectroscopy, high-energy X-ray diffraction and 31P and 23Na solid-state magic angle spinning nuclear magnetic resonance, the atomic structure of coacervate PBGs in the system P2O5-CaO-Na2O-MOx (M = Cu or Zn) with loadings of 2, 10 and 15 mol % of M2+ have been studied as functions of composition and calcination temperature. After drying at room temperature, the structures of the phosphate network in PBG-Cu and PBG-Zn are quite similar, with that of PBG-Zn exhibiting slightly higher connectivity. Heating at 300 °C causes degradation of the polyphosphate chains, even though Q2 species remain predominant. X-ray photoelectron spectroscopy demonstrates that Cu in calcined PBGs is present in both oxidation states +1 and +2, with a predominance of the +2 state. Cu and Zn ion release data after 24 h exposure of PBGs in deionized water and cell medium DMEM show that release is proportional to their loadings. Cytotoxicity MTT assays of dissolution products of PBG-Cu/ZnX calcined at 300 °C on human osteosarcoma cells (MG-63) and on human skin cells (HaCaTs) showed good cellular response for all compositions, indicating that PBGs have great potential for both hard and soft tissue regeneration.

Introduction and overview on autogenous Platelet concentrates.

This special issue on autologous platelet concentrates (APCs) provides clinicians with an overview on the current understanding of the use of these biomaterials for soft and hard-tissue regeneration. The included papers summarize scientific evidence and the clinical findings, presented in simple tables that outline potential benefits including Patient Reported Outcome Measures (PROMs). This approach enables clinicians to assess clinical relevance and researchers to identify significant gaps in the literature. The first part provides a comprehensive summary of the basic science surrounding APC, with particular focus on their preparation methods. Clear recommendations are outlined, which are crucial for obtaining high-quality APCs, alongside an exploration of how APCs may influence both soft and hard tissue healing processes. Part 2 delves into the clinical evidence for the potential benefits of APCs across a range of applications: alveolar ridge preservation, sinus floor elevation, periodontal plastic surgery, guided tissue regeneration, guided bone regeneration, the healing of Medication-Related Osteonecrosis of the Jaw (MRONJ), and endodontic surgery. In the part 3, the discussion turns to the effects of APCs on the healing of extra-oral wounds, including diabetic foot ulcers, venous leg ulcers, pressure injuries, burns, and more. For those clinicians persuaded by the evidence, the fourth section offers a detailed, step-by-step flowchart for each treatment modality, providing a clear guide for clinical application.

Advances in Zinc-Containing Bioactive Glasses: A Comprehensive Review.

Bioactive glasses (BGs) have attracted significant attention in the biomaterials field due to their ability to promote soft and hard tissue regeneration and their potential for various clinical applications. BGs offer enriched features through the integration of different therapeutic inorganic ions within their composition. These ions can trigger specific responses in the body conducive to a battery of applications. For example, zinc, a vital trace element, plays a role in numerous physiological processes within the human body. By incorporating zinc, BGs can inhibit bacterial growth, exert anti-inflammatory effects, and modify bioactivity, promoting better integration with surrounding tissues when used in scaffolds for tissue regeneration. This article reviews recent developments in zinc-containing BGs (ZBGs), focusing on their synthesis, physicochemical, and biological properties. ZBGs represent a significant advancement in applications extending beyond bone regeneration. Overall, their biological roles hold promise for various applications, such as bone tissue engineering, wound healing, and biomedical coatings. Ongoing research continues to explore the potential benefits of ZBGs and to optimize their properties for diverse clinical applications.

Unraveling Nanomaterials in Biomimetic Mineralization of Dental Hard Tissue: Focusing on Advantages, Mechanisms, and Prospects.

The demineralization of dental hard tissue imposes considerable health and economic burdens worldwide, but an optimal method that can repair both the chemical composition and complex structures has not been developed. The continuous development of nanotechnology has created new opportunities for the regeneration and repair of dental hard tissue. Increasingly studies have reported that nanomaterials (NMs) can induce and regulate the biomimetic mineralization of dental hard tissue, but few studies have examined how they are involved in the different stages, let alone the relevant mechanisms of action. Besides their nanoscale dimensions and excellent designability, NMs play a corresponding role in the function of the raw materials for mineralization, mineralized microenvironment, mineralization guidance, and the function of mineralized products. This review comprehensively summarizes the advantages of NMs and examines the specific mineralization mechanisms. Design strategies to promote regeneration and repair are summarized according to the application purpose of NMs in the oral cavity, and limitations and development directions in dental hard tissue remineralization are proposed. This review can provide a theoretical basis to understand the interaction between NMs and the remineralization of dental hard tissue, thereby optimizing design strategy, rational development, and clinical application of NMs in the field of remineralization.

Biologics Agents in Periodontal Regeneration:A Review

The field of periodontology and dental implantology has witnessed significant advancements in the use of molecular mediators and biologic agents over the past decade. Periodontal regeneration, which involves the complete restoration of cementum, bone, and connective tissue following removal of epithelial tissues, is considered superior to tissue repair. Recent research has focused on utilizing biologic materials as complementary therapies to enhance regeneration by accelerating wound healing. These biologic agents were investigated using the following search terms: tissue engineering, intercellular signaling molecules, and biological factors. Enamel matrix derivative (EMD), platelet-derived growth factor (PDGF), platelet-rich plasma, bone morphogenetic proteins (BMPs), fibroblast growth factor (FGF), and parathyroid hormone (PTH) have demonstrated the capacity to stimulate both hard and soft tissue regeneration. However, no single biologic agent is universally effective, necessitating a case-by-case evaluation for optimal treatment selection. Currently, EMD and PDGF are the only biologic therapies approved by the FDA for periodontal regeneration, while BMP-2 is indicated for bone augmentation. Due to a lack of FDA approval for periodontal applications, the clinical use of FGF and PTH in this context is not recommended.

Antimicrobial, remineralization, and infiltration: advanced strategies for interrupting dental caries

Abstract Dental caries, driven by plaque biofilm, poses a major oral health challenge due to imbalance in mineralization and demineralization. The primary objective in caries management is to maintain biofilm homeostasis while facilitating the repair and regeneration of dental hard tissues, thus restoring both structural integrity and functionality of affected teeth. Though antimicrobial and remineralization approaches haven shown promise, their standalone utilization without concurrent bacterial control or rebalancing lacks an integrated strategy to effectively arrest caries progression. Furthermore, according to the principles of minimally invasive dentistry, treatment materials should exhibit high permeability to ensure optimal sealing of demineralized tooth surfaces. The concept of interrupting dental caries (IDC) has emerged as a holistic approach, drawing upon extensive research encompassing three pivotal techniques: antibacterial strategies, remineralization therapies, and infiltration mechanisms, all of which are indispensable components in combating the progression of dental caries. In this review, we provide a comprehensive overview of the mechanisms and applications of antibacterial, remineralization, and infiltration technologies within the context of caries management. Additionally, we summarize advanced materials that align with the IDC concept, aiming to offer valuable insights for designing next-generation materials adept at preventing or halting caries progression efficiently.

Injectable Dual Fenton/Enzymatically Cross-Linked Double-Network Hydrogels Based on Acrylic/Phenolic Polymers with Highly Reinforced and Tunable Mechanical Properties.

Injectable hydrogels have been extensively used as promising therapeutic scaffolds for a wide range of biomedical applications, such as tissue regeneration and drug delivery. However, their low fracture toughness and brittleness often limit their scope of application. Double-network (DN) hydrogel, which is composed of independently cross-linked rigid and ductile polymer networks, has been proposed as an alternative technique to compensate for the weak mechanical properties of hydrogels. Nevertheless, some challenges still remain, such as the complicated and time-consuming process for DN formation, and the difficulty in controlling the mechanical properties of DN hydrogels. In this study, we introduce a simple, rapid, and controllable method to prepare in situ cross-linkable injectable DN hydrogels composed of acrylamide (AAm) and 4-arm-PPO-PEO-tyramine (TTA) via dual Fenton- and enzyme-mediated reactions. By varying the concentration of Fenton's reagent, the DN hydrogels were rapidly formed with controllable gelation rate. Importantly, the DN hydrogels showed a 13-fold increase in compressive strength and a 14-fold increase in tensile strength, compared to the single network hydrogels. The mechanical properties, elasticity, and plasticity of DN hydrogels could also be modulated by simply varying the preparation conditions, including the cross-linking density and reagent concentrations. At low cross-linker concentration (<0.05 wt %), the plastic DN hydrogel stretched to over 6,500%, whereas high cross-linker concentration (≥0.05 wt %) induced fully elastic hydrogels, without hysteresis. Besides, DN hydrogels were endowed with rapid self-recovery and highly enhanced adhesion, which can be further applied to wearable devices. Moreover, human dermal fibroblasts treated with DN hydrogels retained viability, demonstrating the biocompatibility of the cross-linking system. Therefore, we expect that the dual Fenton-/enzyme-mediated cross-linkable DN hydrogels offer great potential as advanced biomaterials applied for hard tissue regeneration and replacement.

Extracellular Vesicles from Compression-Loaded Cementoblasts Promote the Tissue Repair Function of Macrophages.

Treatment strategies for hard tissue defects aim to establish a mineralized microenvironment that facilitates tissue remodeling. As a mineralized tissue, cementum shares a similar structure with bone and exhibits an excellent capacity to resist resorption under compression. Macrophages are crucial for mineralized remodeling; however, their functional alterations in the microenvironment of cementum remain poorly understood. Therefore, this study explores the mechanisms by which cementum resists resorption under compression and the regulatory roles of cementoblasts in macrophage functions. As a result, extracellular vesicles from compression-loaded cementoblasts (Comp-EVs) promote macrophage M2 polarization and enhance the clearance of apoptotic cells (efferocytosis) by 2- to 3-fold. Local injection of Comp-EVs relieves cementum destruction in mouse root resorption model by activating the tissue repair function of macrophages. Moreover, Comp-EV-loaded hydrogels achieve significant bone healing in calvarial bone defect. Unexpectedly, under compression, EV secretion in cementoblasts is reduced by half. RNA-Seq analysis and verification reveal that Rab35 expression decreases by 60% under compression, thereby hampering the release of EVs. Rab35 overexpression is proposed as a modification of cementoblasts to boost the yield of Comp-EVs. Collectively, Comp-EVs activate the repair function of macrophages, which will be a potential therapeutic strategy for hard tissue repair and regeneration.

Biomimetic Bi3+ substituted borate bioactive glasses for bone tissue engineering via enhanced biological and antimicrobial activity

Biomimetic borate-based bioactive glasses (BAGs), substituted with metal oxides, serve as prominent candidates for the repair and regeneration of both hard and soft tissues. In the current study, bismuth mixed borate BAGs (60-X) B2O3–25CaO–15Na2O–XBi2O3 (X = 2, 4, 6, 8 & 10 mol.%) were synthesized using melt-quench method and systematically evaluated for their structural properties, followed by in-vitro biological performance and enhanced antimicrobial activity, using various characterization techniques and bioassays. The BAG structure was studied by Fourier transform infrared (FTIR), differential thermal analysis (DTA), and X-ray photoelectron spectroscopy (XPS) methods. The density and mechanical properties of the BAGs were found to increase with increase in bismuth content of the borate glass network. The XPS analysis confirmed the presence of Bi3+ ions embedded in the glass network. From DTA, it is noticed that the glass transition temperature (Tg) decreased and thermal stability (ΔT) values increased, with increased Bi2O3 content. Further, the bioactivity via hydroxy apatite (HAp) layer formation was confirmed by X-ray diffraction (XRD), FTIR, scanning electron microscopy- energy dispersive spectra (SEM-EDS) and Atomic force microscopy (AFM), both before and after soaking the glass samples in simulated body fluid (SBF) for 0, 7, 14, and 21 days. The results revealed that Bi3+ modified borate BAGs exhibited good HAp layer formation on their surfaces upon immersion in SBF solution. Moreover, the pH variation and degradation followed a trend, with increased in immersion time and decrease with Bi2O3 content. Lastly, in vitro cell culture tests on MG-63 osteoblast-like cells demonstrated that the as-developed BAGs were non-toxic and cytocompatible in nature; in addition, they also displayed demonstrable antibacterial activity against S. aureus and E. coli bacterial strains. Thus, the developed Bi2O3 mixed borate BAGs become suitable candidates for bone substitutes, especially for bone tissue regeneration and repair applications.

Flexible, electrospun boron nitride nanosheets (BNNS)/hydroxyapatite –PVDF nanofibers with superior piezoelectric/ferroelectric, biocompatible features for effective bone tissue regeneration

Piezoelectric/ferroelectric scaffolds are emerging tools in tissue engineering that offer new platforms for the repair and regeneration of damaged soft and hard tissues by means of electrical stimulation. In line with this, boron nitride nanosheets (BNNS)/hydroxyapatite (H)-polyvinylidene fluoride (PVDF) based piezoelectric electrospun nanofibers were developed for effective bone tissue regeneration. BNNS were prepared through a sequential process involving lithium intercalation, followed by hydrothermal exfoliation. Four distinct sets of nanofibers were prepared by altering the concentration of BNNS (2.5 wt%, 5 wt%, 10 wt%) while maintaining a constant concentration of HAP nanoparticles (2.5 wt%) in the PVDF polymer matrix. The piezoelectric/ferroelectric performance of the PVDF-H-BNNS nanofibers were found to be enhanced with the addition of BNNS. The PVDF-H-BNNS nanofibers, with an effective contact area of 1 cm2, exhibited remarkable piezoelectric characteristics, exhibiting a peak voltage of 13 V and a current of 1.63 µA under the influence of 10 N force at a frequency of 10 Hz, showcasing their exceptional electromechanical response. The cytocompatibility studies of PVDF-H-BNNS nanofibers on MG-63 and HOS cell lines reveals excellent viability of nanofibers, akin to that control. Cell proliferation investigations conducted with MG-63 and HOS cell lines on PVDF-H-BNNS showcased the remarkable biocompatibility of the engineered membranes. The PVDF-H-BNNS piezoelectric nanofibers, having exceptional piezo-response and enhanced cytocompatibility, hold promise as ideal candidates for applications in the field of bone tissue engineering.

Epigenetically rewiring metabolic genes via SIRT6 orchestrates MSC fate determination.

SIRT6 owns versatile types of enzymatic activities as a multitasking protein, including ribosyltransferase and deacetylase. To investigate the epigenetic regulations of SIRT6 on MSC fate determination via histone deacetylation, we used allosteric small molecules specifically controlling its histone 3 deacetylation activities. Results showed that enhanced deacetylation of SIRT6 promoted the ossific lineage commitment of MSC and finally achieved anabolic effects on hard tissues. Mechanistically, H3K9ac and H3K56ac, governed by SIRT6, in MSC orchestrated the transcriptions of crucial metabolic genes, mediating MSC fate determination. Most importantly, our data evidenced that modulating the epigenetic regulations of SIRT6, specifically via enhancing its deacetylation of H3K9ac and H3K56ac, was a promising choice to treat bone loss diseases and promote dentin regeneration. In this study, we revealed the specific roles of SIRT6's histone modification in MSC fate determination. These findings endow us with insights on SIRT6 and the promising therapeutic choices through SIRT6's epigenetic functions for hard tissues regeneration.

Recombinant human fibroblast growth factor and autogenous bone for periodontal regeneration: Alone or in combination? A randomized clinical trial

AbstractAimTo compare the outcomes of therapy using recombinant human fibroblast growth factor (rhFGF)‐2 combined with autologous bone grafting (ABG) therapy with those of rhFGF‐2 alone and ABG alone in the treatment of periodontal intraosseous defects.MethodsPeriodontal intraosseous defects were randomized to receive rhFGF‐2 therapy + ABG, rhFGF‐2 therapy alone, or ABG alone. Periodontal examination and periapical radiography were performed preoperatively and at 3, 6, and 12 months postoperatively.ResultsAt the 12 months follow‐up, all three groups showed significant improvement in the clinical attachment level (CAL): 5.6 ± 1.6, 5.8 ± 1.7, and 5.2 ± 1.6 mm in the rhFGF‐2 + ABG, rhFGF‐2 alone, and ABG alone groups, respectively, with no significant inter‐group differences (p &lt; .05). rhFGF‐2 therapy (alone or in combination) resulted in greater bone defect filling (BDF) (2.3 ± 1.2 mm and 2.6 ± 1.9 mm, respectively) than ABG therapy alone (1.2 ± 1.2 mm). Gingival recession was lesser in the ABG alone (1.2 ± 1.1 mm) and rhFGF‐2 + ABG groups (1.4 ± 0.8 mm) than in the rhFGF‐2 alone group (2.2 ± 1.2 mm).ConclusionThe results of this study showed that at 12 months postoperatively, all treatments resulted in statistically significant clinical improvements compared to the baseline. From these results, it can be concluded that rhFGF‐2 promotes hard tissue regeneration in intraosseous defects.

Importance of Biopolymers in Pharmaceutical and Medical Fields

Biopolymers have gained significant traction in the pharmaceutical and medical fields due to their unique properties and versatile applications. These naturally derived polymers exhibit remarkable characteristics such as biodegradability, biocompatibility, renewability, affordability, and availability. Their role in tissue engineering, wound healing, and biosensor development has been extensively explored. In tissue engineering, biopolymers serve as scaffolds or matrices, supporting cell growth, proliferation, and differentiation for both hard and soft tissue regeneration. Hard tissue scaffolds often incorporate biopolymers like collagen, chitosan, and gelatin, combined with bioactive ceramics like hydroxyapatite, mimicking the natural composition of bone. Soft tissue scaffolds employ biopolymers such as collagen, gelatin, elastin, and alginate, fabricated into hydrogels, fibrous meshes, or porous structures for applications like skin, vascular, cardiac, and nerve tissue regeneration. Biopolymers have demonstrated promising potential in promoting wound healing and tissue repair, creating moist wound dressings, absorbing exudates, and providing a favorable environment for tissue regeneration. Biopolymers like collagen, chitosan, and alginate have been investigated for this purpose. In biosensor development, biopolymers offer biocompatibility and the ability to immobilize biomolecules such as enzymes, antibodies, or nucleic acids, serving as matrices for biological recognition elements while maintaining their activity and stability

THE EXPERIENCE OF USING A NEW PHARMACOLOGICALLY ACTIVE COMPOSITION OF NANOSTRUCTURED FLUORAPATITE IN THE TREATMENT OF EARLY MANIFESTATIONS OF INCREASED TOOTH ABRASION

Despite the obvious successes in the field of preventive and conservative dentistry, the prevalence of abrasion of teeth (ITP) continues to grow: during the period 1992-2004, the proportion of diseases of hard tissues of teeth with elimination properties increased from 30.9 ± 1.8% to 38.2 ± 1.3%, i.e. increased by 7.3% [1, 7-10]. Many issues related to the diagnosis and planning of an integrated approach to the provision of dental care to patients with moderate CAH have not yet been sufficiently studied and covered [2]. Biologically active calcium phosphate in gel or colloidal state is currently of increasing interest in many areas of clinical medicine related to the problem of regeneration of soft and hard tissues of the body. It has been established that the biological activity of apatite largely depends on the size of its particles or grains, and the higher the dispersion of the substance, the more pronounced it is [3]. The use of pure compounds, as well as various combinations of bioactive substances to improve properties such as adhesion, bioactivity and biocompatibility, is also very promising [4]. A promising direction of modification of calcium hydroxyapatite (HCA) from the point of view of obtaining materials with improved properties is the introduction of fluorine and silicon atoms into the structure of HCA. This transformation increases the stability of the material in the chemically active environment of the human body (due to the presence of fluoride ions) and increases its biological activity (due to the presence of silicate ions), while maintaining the inherent biocompatibility of HAP [5]. Nanotechnology is used in the study, production and use of nanostructures, devices and systems, including targeted control and modification of the shape, size, interaction and integration of their constituent nanoscale elements (1-100 nm) to obtain objects with new chemical, physical and biological properties. A number of technologies and methods. Direct transport of medicines to the focus of the pathological process can increase the effectiveness of existing drug therapies [6]. A promising direction in modern dentistry is the creation of new pharmacological agents with particle sizes of the order of 10-9 (nanoparticles) for noninvasive treatment and early prevention of dental diseases. The aim of the study was to study the effectiveness of new pharmacologically active compositions of nanostructured fluorohydroxyapatite in the treatment of early symptoms of dental hyperextension.