Periodontium-Mimicking, Multifunctional Biomass-Based Hydrogel Promotes Full-Course Socket Healing.

Preserving stable tooth-periodontal tissue integration is vital for maintaining alveolar bone stability under physiological conditions. However, tooth extraction compromises this integration and impedes socket healing. Therefore, it becomes crucial to provide early stage coverage of the socket to promote optimal healing. Drawing inspiration from the periodontium, we have developed a quaternized methacryloyl chitosan/dopamine-grafted oxidized sodium alginate hydrogel, termed the quaternized methacryloyl chitosan/dopamine-grafted oxidized sodium alginate hydrogel (QDL hydrogel). Through blue-light-induced cross-linking, the QDL hydrogel serves as a comprehensive wound dressing for socket healing. The QDL hydrogel exhibits remarkable efficacy in closing irregular tooth extraction wounds. Its favorable mechanical properties, flexible formability, and strong adhesion are achieved through modifications of chitosan and sodium alginate derived from biomass sources. Moreover, the QDL hydrogel demonstrates a superior hemostatic ability, facilitating swift blood clot formation. Additionally, the inherent antibacterial properties of the QDL hydrogel effectively inhibit oral microorganisms. Furthermore, the QDL hydrogel promotes angiogenesis, which facilitates the nutrient supply for subsequent tissue regeneration. Notably, the hydrogel accelerates socket healing by upregulating the expression of genes associated with wound healing. In conclusion, the periodontium-mimicking multifunctional hydrogel exhibits significant potential as a clinical tooth extraction wound dressing.

Formation and regeneration of a Wnt-responsive junctional epithelium.

AIM: To identify the molecular mechanisms mediating the persistent defensive functions of the self-renewing junctional epithelium (JE). MATERIALS AND METHODS: Two strains of Wnt reporter mice, Axin2CreErt2/+ ;R26RmTmG/+ and Axin2LacZ/+ , were employed, along with three clinically relevant experimental scenarios where the function of the JE is disrupted: after tooth extraction, after a partial gingivectomy, and after a complete circumferential gingivectomy. RESULTS: Using transgenic Wnt reporter strains of mice, we established the JE is a Wnt-responsive epithelium beginning at the time of its formation and that it maintains this status into adulthood. After tooth extraction, progeny of the initial Wnt-responsive JE population directly contributed to healing and ultimately adopted an oral epithelium (OE) phenotype. In the traditional partial gingivectomy model, the JE completely regenerated and did so via progeny of the original Wnt-responsive population. However, following circumferential gingivectomy, the OE was incapable of re-establishing a functional JE. CONCLUSIONS: A Wnt-responsive niche at the interface between tooth and oral epithelia is required for a functional JE.

The effect of haemostatic agents on early healing of the extraction socket.

AIM: This study aims to explore the effect of two commercially available haemostatic agents (i.e., collagen sponge and oxide cellulose) on early healing of the extraction socket. MATERIAL AND METHODS: In a murine model, bilateral maxillary first molars were extracted and the sockets were filled with or without haemostatic agents. Histology, histomorphometry and immunostaining assays were performed on samples harvested on postextraction day 1, 3, 7 and 14. In vitro studies were also designed to investigate the effect of agents on the dynamics of pH and viability of cells. RESULTS: Early socket healing was delayed by both agents but with different patterns. The migration of cells was impeded by oxide cellulose on postextraction day 1 compared with the collagen and the control group. The proliferation and osteogenic differentiation of cells were delayed by both materials. Moreover, apoptosis of periodontal ligament cells was present in the haemostatic agent groups. These effects are attributed to the compression to periodontal ligament by both agents, the acidic niche caused by oxide cellulose, and the intense foreign body reaction and inflammatory response caused by the agents. CONCLUSIONS: The placement of haemostatic agents delay the early extraction socket healing via different biological mechanism.

Screening the Expression Changes in MicroRNAs and Their Target Genes in Mature Cementoblasts Stimulated with Cyclic Tensile Stress.

Cementum is a thin layer of cementoblast-produced mineralized tissue covering the root surfaces of teeth. Mechanical forces, which are produced during masticatory activity, play a paramount role in stimulating cementoblastogenesis, which thereby facilitates the maintenance, remodeling and integrity of cementum. However, hitherto, the extent to which a post-transcriptional modulation mechanism is involved in this process has rarely been reported. In this study, a mature murine cementoblast cell line OCCM-30 cells (immortalized osteocalcin positive cementoblasts) was cultured and subjected to cyclic tensile stress (0.5 Hz, 2000 µstrain). We showed that the cyclic tensile stress could not only rearrange the cell alignment, but also influence the proliferation in an S-shaped manner. Furthermore, cyclic tensile stress could significantly promote cementoblastogenesis-related genes, proteins and mineralized nodules. From the miRNA array analyses, we found that 60 and 103 miRNAs were significantly altered 6 and 18 h after the stimulation using cyclic tensile stress, respectively. Based on a literature review and bioinformatics analyses, we found that miR-146b-5p and its target gene Smad4 play an important role in this procedure. The upregulation of miR-146b-5p and downregulation of Smad4 induced by the tensile stress were further confirmed by qRT-PCR. The direct binding of miR-146b-5p to the three prime untranslated region (3' UTR) of Smad4 was established using a dual-luciferase reporter assay. Taken together, these results suggest an important involvement of miR-146b-5p and its target gene Smad4 in the cementoblastogenesis of mature cementoblasts.

Experts' consensus on perioperative management of tooth extractions in patients receiving oral antithrombotic treatment.

Thromboembolic diseases, which comprise venous thromboembolic diseases and arterial thromboembolic diseases, have become the number one cause of death worldwide. To prevent or treat thrombosis, patients with thromboembolic diseases need to take antithrombotic drugs, which would increase the risk of bleeding during and after surgery. Tooth extraction is the most common operation in oral and maxillofacial surgery clinics. Although patients given oral antithrombotic drugs do not need to undergo drug withdrawal, the perioperative management of such patients remains confusing to most clinicians. Moreover, the potential risk factors for bleeding warrant further study. To improve the clinicians' knowledge of perioperative management for patients subjected to tooth extractions with oral antithrombotic drugs, experts have drafted this consensus focusing on preoperative bleeding risk assessment, intraoperative operating norms, and postoperative care to summarize the points needing attention.

The synergetic effect of bioactive molecule-loaded electrospun core-shell fibres for reconstruction of critical-sized calvarial bone defect-The effect of synergetic release on bone Formation.

OBJECTIVES: Bone regeneration is a complex process modulated by multiple growth factors and hormones during long regeneration period; thus, designing biomaterials with the capacity to deliver multiple bioactive molecules and obtain sustained release has gained an increasing popularity in recent years. This study is aimed to evaluate the effect of a novel core-shell electrospun fibre loaded with dexamethasone (DEX) and bone morphogenetic protein-2 (BMP-2) on bone regeneration. MATERIALS AND METHODS: The core-shell electrospun fibres were fabricated by coaxial electrospinning technology, which were composed of poly-D, L-lactide (PLA) shell and poly (ethylene glycol) (PEG) core embedded with BMP-2 and DEX-loaded micelles. Morphology, hydrophilicity, gradation, release profile of BMP-2 and DEX, and cytological behaviour on bone marrow mesenchymal stem cells (BMSCs) were characterized. Furthermore, the effect on bone regeneration was evaluated via critical-sized calvarial defect model. RESULTS: The electrospun fibres were featured by the core-shell fibrous architecture and a suitable degradation rate. The sustained release of DEX and BMP-2 was up to 562 hours. The osteogenic gene expression and calcium deposition of BMSCs were significantly enhanced, indicating the osteoinduction capacity of electrospun fibres. This core-shell fibre could accelerate repair of calvarial defects in vivo via synergistic effect. CONCLUSIONS: This core-shell electrospun fibre loaded with DEX and BMP-2 can act synergistically to enhance bone regeneration, which stands as a strong potential candidate for repairing bone defects.

Survivorship comparison of all-polyethylene and metal-backed tibial components in cruciate-substituting total knee arthroplasty--Chinese experience.

Considering its cost saving, the all-polyethylene tibial component is of potential interest in developing countries like China. But to our knowledge, a survivorship comparison of all-polyethylene and metal-backed tibial components in posterior cruciate ligament-substituting total knee arthroplasty (PS-TKA) has not been studied in China previously. Using survivorship analysis, we have studied the midterm outcome of 34 cemented PS-TKA using an all-polyethylene tibial component and of 34 cemented PS-TKA using a metal-backed tibial component which has an identical articular surface with all-polyethylene tibial components. All operations were performed by the same group of surgeons; 58 patients underwent a unilateral operation and five patients a bilateral operation. These patients had a mean follow-up of 5.9 years (range: 5-7 years); three patients were lost to follow-up and one was revised for infection. No significant difference between the two groups was reported regarding HSS scores, ROM, clinical and radiographic parameters measured and survival rates. Although the Asian lifestyle includes more squatting and bending of the knee, the results of this series of TKA using all-polyethylene tibial components in Chinese people are comparable to the satisfactory results of other reported all-polyethylene series whose patients are mainly Western people. Considering its cost saving and excellent clinical result, the all-polyethylene tibial component is of potential interest in developing countries.

Aberrantly elevated Wnt signaling is responsible for cementum overgrowth and dental ankylosis.

Vertebrate teeth are attached to the jawbones using a variety of methods but in mammals, a fibrous connection is the norm. This fibrous periodontal ligament (PDL) allows teeth to move in the jawbones in response to natural eruptive forces, mastication, and orthodontic tooth movement. In some disease states the PDL either calcifies or is replaced by a mineralized tissue and the result is ankylosis, where the tooth is fused to the alveolar bone. To understand how the PDL maintains this fibrous state, we examined a strain of mice in which tooth movement is arrested. DaßcatOt mice express a stabilized form of ß-catenin in DMP1-positive alveolar bone osteocytes and cementocytes, which results in elevated Wnt signaling throughout the periodontium. As a consequence, there is an accrual of massive amounts of cellular cementum and alveolar bone, the PDL itself calcifies and teeth become ankylosed. These data suggest that to maintain its fibrous nature, Wnt signaling must normally be repressed in the PDL space.

An osteopenic/osteoporotic phenotype delays alveolar bone repair.

Aging is associated with a function decline in tissue homeostasis and tissue repair. Aging is also associated with an increased incidence in osteopenia and osteoporosis, but whether these low bone mass diseases are a risk factor for delayed bone healing still remains controversial. Addressing this question is of direct clinical relevance for dental patients, since most implants are performed in older patients who are at risk of developing low bone mass conditions. The objective of this study was to assess how an osteopenic/osteoporotic phenotype affected the rate of new alveolar bone formation. Using an ovariectomized (OVX) rat model, the rates of tooth extraction socket and osteotomy healing were compared with age-matched controls. Imaging, along with molecular, cellular, and histologic analyses, demonstrated that OVX produced an overt osteoporotic phenotype in long bones, but only a subtle phenotype in alveolar bone. Nonetheless, the OVX group demonstrated significantly slower alveolar bone healing in both the extraction socket, and in the osteotomy produced in a healed extraction site. Most notably, osteotomy site preparation created a dramatically wider zone of dying and dead osteocytes in the OVX group, which was coupled with more extensive bone remodeling and a delay in the differentiation of osteoblasts. Collectively, these analyses demonstrate that the emergence of an osteoporotic phenotype delays new alveolar bone formation.

Biophysical regulation of osteotomy healing: An animal study.

BACKGROUND: Osteotomies have been performed for centuries yet there remains a remarkable lack of consensus on optimal methods for cutting bone. There is universal agreement, however, that preserving cell viability is critical. PURPOSE: To identify mechanobiological parameters influencing bone formation after osteotomy site preparation. MATERIALS AND METHODS: A murine maxillary osteotomy model was used to evaluate healing. Computational modeling characterized stress and strain distributions in the osteotomy, as well as the magnitude and distribution of heat generated by drilling. The impact of osteocyte death and bone composition were assessed using molecular and cellular assays. RESULTS: The phases of osteotomy healing in mice align closely with results in large animals; in addition, molecular analyses extended our understanding of osteoprogenitor cell proliferation, differentiation, and mineralization. Computational analyses provided insights into temperature changes caused by drilling and the mechanobiological state in the healing osteotomies, while concomitant cellular assays correlate drill speed with osteocyte apoptosis and bone resorption. Even when drilling was controlled, trabeculated, spongy (Type III) bone healed faster than densely lamellar (Type I) bone because of the abundance of Wnt responsive osteoprogenitor cells in the former. CONCLUSIONS: These data provide a mechanobiological framework for evaluating tools and technologies designed to improve osteotomy site preparation.

Ectopic osteoid and bone formation by three calcium-phosphate ceramics in rats, rabbits and dogs.

Calcium phosphate ceramics with specific physicochemical properties have been shown to induce de novo bone formation upon ectopic implantation in a number of animal models. In this study we explored the influence of physicochemical properties as well as the animal species on material-induced ectopic bone formation. Three bioceramics were used for the study: phase-pure hydroxyapatite (HA) sintered at 1200°C and two biphasic calcium phosphate (BCP) ceramics, consisting of 60 wt.% HA and 40 wt.% TCP (ß-Tricalcium phosphate), sintered at either 1100°C or 1200°C. 108 samples of each ceramic were intramuscularly implanted in dogs, rabbits, and rats for 6, 12, and 24 weeks respectively. Histological and histomorphometrical analyses illustrated that ectopic bone and/or osteoid tissue formation was most pronounced in BCP sintered at 1100°C and most limited in HA, independent of the animal model. Concerning the effect of animal species, ectopic bone formation reproducibly occurred in dogs, while in rabbits and rats, new tissue formation was mainly limited to osteoid. The results of this study confirmed that the incidence and the extent of material-induced bone formation are related to both the physicochemical properties of calcium phosphate ceramics and the animal model.