Dual Blockade of TNF and IL-17A Inhibits Inflammation and Structural Damage in a Rat Model of Spondyloarthritis

The tumor necrosis factor (TNF) and IL-23/IL-17 axes are the main therapeutic targets in spondyloarthritis. Despite the clinical efficacy of blocking either pathway, monotherapy does not induce remission in all patients and its effect on new bone formation remains unclear. We aimed to study the effect of TNF and IL-17A dual inhibition on clinical disease and structural damage using the HLA-B27/human β2-microglobulin transgenic rat model of SpA. Immunized rats were randomized according to arthritis severity, 1 week after arthritis incidence reached 50%, to be treated twice weekly for a period of 5 weeks with either a dual blockade therapy of an anti-TNF antibody and an anti-IL-17A antibody, a single therapy of either antibody, or PBS as vehicle control. Treatment-blinded observers assessed inflammation and structural damage clinically, histologically and by micro-CT imaging. Both single therapies as well as TNF and IL-17A dual blockade therapy reduced clinical spondylitis and peripheral arthritis effectively and similarly. Clinical improvement was confirmed for all treatments by a reduction of histological inflammation and pannus formation (p < 0.05) at the caudal spine. All treatments showed an improvement of structural changes at the axial and peripheral joints on micro-CT imaging, with a significant decrease for roughness (p < 0.05), which reflects both erosion and new bone formation, at the level of the caudal spine. The effect of dual blockade therapy on new bone formation was more prominent at the axial than the peripheral level. Collectively, our study showed that dual blockade therapy significantly reduces inflammation and structural changes, including new bone formation. However, we could not confirm a more pronounced effect of dual inhibition compared to single inhibition.

The Ability and Mechanism of nHAC/CGF in Promoting Osteogenesis and Repairing Mandibular Defects

Nano-hydroxyapatite/collagen (nHAC) is a new type of bone tissue engineering scaffold material. To speed up the new bone formation of nHAC, this study used concentrated growth factor (CGF) and nHAC in combination to repair rabbit mandibular defects. nHAC/CGF and nHAC were implanted into rabbit mandibles, and X-ray, Micro-CT, HE and Masson staining, immunohistochemical staining and biomechanical testing were performed at 8, 16 and 24 weeks after surgery. The results showed that as the material degraded, the rate of new bone formation in the nHAC/CGF group was better than that in the nHAC group. The results of the HE and Masson staining showed that the bone continuity or maturity of the nHAC/CGF group was better than that of the nHAC group. Immunohistochemical staining showed that OCN expression gradually increased with time. The nHAC/CGF group showed significantly higher BMP2 than the nHAC group at 8 weeks and the difference gradually decreased with time. The biomechanical test showed that the compressive strength and elastic modulus of the nHAC/CGF group were higher than those of the nHAC group. The results suggest that nHAC/CGF materials can promote new bone formation, providing new ideas for the application of bone tissue engineering scaffold materials in oral clinics.

Autologous Tooth Dentin Graft: A Retrospective Study in Humans

Background and Objectives: The aim of this study is to evaluate the efficacy of an autologous dentin graft, via extracted teeth that are processed into bacteria-free particulate dentin in a Smart dentin grinder and then grafted immediately into alveolus post extraction or into bone deficiencies. Materials and Methods: Ten healthy, partially edentulous patients with some teeth in the mandible were recruited in the study. After their own teeth were grinded, particulate teeth were placed in empty sockets and bone defects after teeth extractions. Furthermore, after three, six, 12 and 24 months, core samples using a 3 mm trephine were obtained. Results: At three months, the particles of grinded tooth were immersed inside a new connective tissue with a small new bone formation (16.3 ± 1.98). At six months, we observed small particles of dentin integrated in new immature bone, without inflammation in the soft tissue (41.1 ± 0.76). At twelve months, we observed a high amount of bone formation surrounding tooth particles (54.5 ± 0.24), and at twenty-four months, new bone, a big structure of bone, was observed with dentin particles (59.4 ± 1.23), statistically different when compared it with at three months. Conclusions: A particulate dentin graft should be considered as an alternative material for sockets’ preservation, split technique, and also for sinus lifting. One of the special characteristics after 24 months of evaluation was the high resorption rate and bone replacement without inflammation. This material could be considered as an acceptable biomaterial for different bone defects due to its osteoinductive and osteoconductive properties

Horizontal Augmentation of Chronic Mandibular Defects by the Guided Bone Regeneration Approach: A Randomized Study in Dogs

Various biomaterial combinations have been studied focusing on their ability to stabilize blood clots and maintain space under soft tissue to support new bone formation. A popular combination is Deproteinized Bovine Bone Mineral (DBBM) placed with a native collagen membrane (NCM) tacked to native bone. In this study, we compared the outcome of this treatment option to those achieved with three different graft/membrane combinations with respect to total newly occupied area and the mineralized compound inside. After bi-lateral extraction of two mandibular premolars in five adult beagles L-shaped alveolar defects were created. A total of 20 defects healed for 6 weeks resulting in chronic type bone defects. At baseline, four options were randomly allocated to five defects each: a. DBBM + NCM with a four-pin fixation across the ridge; b. DBBM + RCLC (ribose cross-linked collagen membrane); c. DBBM + NPPM (native porcine pericardium membrane); and d. Ca-sulfate (CS) + RCLC membrane. Membranes in b/c/d were not fixed; complete tensionless wound closure was achieved by CAF. Termination after 3 months and sampling followed, and non-decalcified processing and toluidine blue staining were applied. Microscopic images obtained at standardized magnification were histomorphometrically assessed by ImageJ software (NIH). An ANOVA post hoc test was applied; histomorphometric data are presented in this paper as medians and interquartile ranges (IRs). All sites healed uneventfully, all sites were sampled and block separation followed before Technovit embedding. Two central sections per block for each group were included. Two of five specimen were lost due to processing error and were excluded from group b. New bone area was significantly greater for option b. compared to a. (p = 0.001), c. (p = 0.002), and d. (p = 0.046). Residual non-bone graft area was significantly less for option d. compared to a. (p = 0.026) or c. (p = 0.021). We conclude that collagen membranes with a prolonged resorption/barrier profile combined with bone substitutes featuring different degradation profiles sufficiently support new bone formation. Tacking strategy/membrane fixation appears redundant when using these biomaterials.

Sustained Release of Vitamin D3 Enhanced Osseointegration Capacity: An Experimental Sheep Study

This study aimed to investigate the effect of sustained-release vitamin D loaded in poly-lactic acid (PLA) nanoparticles and applied to grafting materials around titanium (ti) dental implants. A total of 48 implants were inserted into the standardized bone defects created in the iliac crest of 6 sheep, divided into 4 different experimental sites (empty control, autografted, xenografted, and autograft + xenografted). Vitamin D3, which was encapsulated by PLA nanoparticles, was prepared and applied in half of the defects and left to heal for 3 and 6 weeks. New bone formation (NBF%) and bone-implant contact (BIC%) values were evaluated by histologic and histomorphometric analyses (P < 0.05). Nanoparticles with a yield of 80.30% ± 2.14% and high encapsulation efficiency of 72.99% ± 2.20% were achieved. In all sections, osseointegration was observed, with no signs of inflammation, necrosis, or foreign body reaction. NBF% and BIC% were significantly higher in vitamin D3–loaded groups (P < 0.001). In both healing periods, the highest NBF% and BIC% have been recorded in the autograft + xenograft groups. (For the respective third and sixth weeks: the NBF% was 49.63 ± 1.53 and 74.25 ± 0.96, and BIC% was 54.26 ± 0.66 and 82.59 ± 2.09, respectively; P < 0.001). Sustained-release of vitamin D loaded into the PLA system demonstrated high biocompatibility, favorable sustained release of vitamin D3, and improved NBF% and BIC% around ti implants placed in box-shaped sheep iliac crest defects. Further investigations are required for their clinical applicability.

A possible case of Gigantism and/or Acromegaly in a 15th-17th century woman from Đurine Ćelije, Serbia

Endocrine disorders during growth and development that occur due to the secretion of excessive growth hormones are very rare in archaeological and modern populations. The human skeletal remains analyzed in this paper belong to an unusually tall woman, approximately 35-40 years of age, buried at the Đurine ćelije site (15th-17th century) in Serbia, who may have suffered from overgrowth syndrome. Individuals with this condition have an unusually tall stature and accompanying pathological changes related to organ systems and joint diseases. The aim of this paper is to show how the aforementioneddisorder affected the health status of an individual (grave No. 7a) and the performance of daily activities, but also the attitude of the community towards deformities during life and after death. Differential diagnosis was performed since otherdiseases tend to lead to similar skeletal changes. During the analysis, changes in growth were noticed, and her stature was determined to be 186.42 cm. Compared to the documented stature of post-medieval population from this period, theskeletal remains show a significant deviation from the average, especially when it comes to female individuals. Other pathological changes observed in this woman are osteoarthritis, spondyloarthropathy, and periosteal new bone formation.

Supercritical Carbon Dioxide Decellularized Bone Matrix Seeded with Adipose-Derived Mesenchymal Stem Cells Accelerated Bone Regeneration

Large bone fractures with segmental defects are a vital phase to accelerate bone integration. The present study examined the role of supercritical carbon dioxide (scCO2) decellularized bone matrix (scDBM) seeded with allogeneic adipose-derived mesenchymal stem cells (ADSC) as bio-scaffold for bone regeneration. Bio-scaffold produced by seeding ADSC to scDBM was evaluated by scanning electron microscopy (SEM). Rat segmental femoral defect model was used as a non-union model to investigate the callus formation in vivo. Histological analysis and osteotomy gap closure in the defect area were analyzed at 12 and 24 weeks post-surgery. Immunohistochemical expression of Ki-67, BMP-2 and osteocalcin was evaluated to assess the ability of new bone formation scDBM. ADSC was found to attach firmly to scDBM bioscaffold as evidenced from SEM images in a dose-dependent manner. Callus formation was observed using X-ray bone imaging in the group with scDBM seeded with 2 × 106 and 5 × 106 ASCs group at the same time-periods. H&E staining revealed ASCs accelerated bone formation. IHC staining depicted the expression of Ki-67, BMP-2, and osteocalcin was elevated in scDBM seeded with 5 × 106 ASCs group at 12 weeks after surgery, relative to other experimental groups. To conclude, scDBM is an excellent scaffold that enhanced the attachment and recruitment of mesenchymal stem cells. scDBM seeded with ASCs accelerated new bone formation.