Osseous Tissue Formation Research Articles

The Effect of Human Demineralized Dentin Matrix Scaffold Alone and Combined with Concentrated Growth Factor on Bone Repair in Rabbits

Purpose: This study aimed to evaluate the potential effect of Human Demineralized Dentin Scaffold (HDDS) alone and when combined with Concentrated Growth Factor (CGF) on repair of bony defects in the tibia of rabbits, histologically, by using scanning electron microscope and computed tomography. Materials and Methods: Ten adult male rabbits (weight 2 to 2.5 kg) were used in this study. Ethics committee approval of Faculty of Dental Medicine For Girls as obtained with code number (REC-BI-19-01). In each rabbit two holes were created (one in each tibia). In five rabbits, the first control hole was left empty and the second was packed with CGF. In the other five rabbits, one hole was packed with DDM slices from anonymous human permanent teeth without carious lesion or other pathology and the second was packed with DDM and CGF. The rabbits were euthanized at 1 and 6 weeks postoperatively and the bone samples were processed for histological analysis. Results: Faster bone repair was occurred in the experimental groups. In all groups, Osteoid tissue formation was occurred at one week, and osseous tissue formation was seen filling the bone defects at 6 weeks. The best results after 6 weeks appeared in surgical bone defects grafted with HDDS and CGF where the new bone showed better organization than the HDDS alone and CGF alone and most of the formed osteons were fully compacted. Conclusion: Combining Human Demineralized Dentin Scaffold (HDDS) with concentrated growth factor (CGF) improved graft biomaterial when used as xenograft and it became more effective through inducing a faster bone repair.

Repairing a critical cranial defect using WISP1-pretreated chondrocyte scaffolds

In cranial flat bone fractures, spontaneous bone repair will occur only when the fracture ends are in close contact. However, in cases wherein bone discontinuity is extensive, surgical interventions are often required. To this end, autologous bone is harvested and surgically integrated into the site of fracture. Here we propose to use cartilage, as an alternative autologous source, to promote cranial fracture repair. The advantage of this approach is the potential reduction in donor site morbidity, likely due to the avascular and aneural nature of cartilage. As a first step we attempted to induce cartilage mineralization in vitro, using micromass primary chondrocyte cultures, incubated with BMP2 and/or WISP1, which were examined histologically following a 3-week culture period. Next, chondrocyte seeded collagen scaffolds were evaluated in vitro for expression profiles and ALP activity. Finally, chondrocyte-seeded collagen scaffolds were implanted in a Lewis rats 8 mm critical calvaria defect model, which was imaged via live CT for 12 weeks until sacrifice. End points were analyzed for microCT, histology, and serum levels of bone related markers. Micromass cultures exhibited an osseous inducing trend following WISP1 administration, which was maintained in chondrocyte seeded scaffolds. Accordingly, in vivo analysis was carried out to assess the impact of WISP1-pretreated chondrocytes (WCS) versus untreated chondrocytes (UCS) in calvaria defect model and compared to untreated control comprised of a defect-associated blood clot (BC) or empty collagen scaffold (CS) implant. Live CT and microCT exhibited higher mineralization volumes in critical defect implanted with UCS, with some structural improvements in WCS. Histological analysis exhibited higher anabolic bone formation in WCS and trabecular bone was detected in WCS and UCS groups. Chondrocytes implanted into critical cranial defect expedite the formation of native-like osseous tissue, especially after WISP1 priming in culture. Ultimately, these data support the use of autologous chondrocytes to repair critical maxillofacial defects.

In vivo biocompatibility of SrO and MgO doped brushite cements.

The addition of dopants in biomaterials has emerged as a critical regulator of bone formation and regeneration due to their imminent role in the biological process. The present work evaluated the role of strontium (Sr) and magnesium (Mg) dopants in brushite cement (BrC) on in vivo bone healing performance in a rabbit model. Pure, 1wt% SrO (Sr-BrC), 1wt% MgO (Mg-BrC), and a binary composition of 1.0wt% SrO + 1.0wt% MgO (Sr + Mg-BrC) BrCs were implanted into critical-sized tibial defects in rabbits for up to 4months. The in vivo bone healing of three doped and pure BrC samples was examined and compared using sequential radiological examination, histological evaluations, and fluorochrome labeling studies. The results indicated excellent osseous tissue formation for Sr-BrC and Sr + Mg-BrC and moderate bone regeneration for Mg-BrC compared to pure BrC. Our findings indicated that adding small amounts of SrO, MgO, and binary dopants to the BrC can significantly influence new bone formation for bone tissue engineering.

The Effect of Mineralized Plasmatic Matrix and Chitosan on the Healing of Critical-Sized Mandibular Bone Defects in a Rabbit Model

Background: In maxillofacial surgery, critical size mandibular defects remain a challenging issue. There have been numerous attempts to improve mandibular defect healing. Recently, bone tissue engineering has provided many benefits in improving bone healing. Herein, we tried to investigate the effect of Mineralized plasmatic matrix (MPM) and Chitosan to enhance tissue healing and regeneration in mandibular bone defect. Methods: A mandibular bone defect of critical size was created in 45 New Zealand rabbits. There were three groups of rabbits: the MPM group, the Chitosan group, and the control group. Radiographical, histological, and immune histochemical evaluations were performed at 4, 8, and 12 post-operative weeks. Results: The MPM group demonstrated the highest degree of bone formation with uniform radio-opacity nearly like that of adjacent healthy parent tissue. While in the chitosan group, most of the defect area was filled with radio-opaque bone with persistent small radiolucent areas. The control group showed less bone formation than the MPM and chitosan group, with more radiolucent areas. Sections stained with (H&E) demonstrated an increase in osseous tissue formation in both the MPM and chitosan groups. Staining with Masson’s trichrome revealed an increase in fibrous connective tissue proliferation in both the MPM and chitosan groups. In both the MPM and chitosan groups, nuclear factor kappa p65 was downregulated, and matrix metalloproteinase-9 was upregulated. Conclusion: According to the current study, MPM and Chitosan may have beneficial effects on the healing of critical-sized mandibular bone defects.

A bilineage thermosensitive hydrogel system for stimulation of mesenchymal stem cell differentiation and enhancement of osteochondral regeneration

Osteochondral lesions in weight-bearing joints often fail to heal due to their poor intrinsic repair capacity and may lead to severe complications such as osteoarthritis. This study investigated the chondrogenesis, osteogenesis, and regenerative potential of an injectable, thermoresponsive chitosan-graft-poly(N-isopropylacrylamide) (CS-g–PNIPAAm, or CSPN) hydrogel combined with infrapatellar fat pad-derived mesenchymal stem cell (IFPSC) and platelet-rich plasma (PRP) with regard to osteochondral regeneration. CSPN hydrogels were prepared and characterized using several procedures. Optimal CSPN hydrogel (CSPN hydrogel with 67% of PNIPAAm, or CSPN05) was examined following a biochemical assay and animal implantation. PRP incorporated CSPN05 hydrogel, CSPN05-PRP, was fabricated. We found that rabbit IFPSCs (rIFPSCs) cultured in the CSPN05-PRP hydrogel (rIFPSC–CSPN05–PRP) enhanced the expression of chondrogenic and osteogenic genes after 1, 3, 5, and 7 days of culture and significantly increased sulfated glycosaminoglycan content, alkaline phosphatase activity, and mineralization after 5 and 7 days of culture compared with PN and CSPN05. In addition, PRP induced the expression of specific signaling molecules for chondrogenesis and osteogenesis in its signaling pathway . A preliminary in vivo study showed that rIFPSC-CSPN05–PRP could effectively regenerate the osteochondral defect at 4 weeks. Thus, the combination of IFPSC, the CSPN hydrogel, and PRP can synergistically enhance chondrogenic and osteogenic gene expression, cartilage- and bone-specific extracellular matrix production, hyaline cartilage regeneration, and mineralized osseous tissue formation. CSPN scaffolds with PRP show potential as biomaterial by providing mechanical support for cell growth and inducing stem cells to differentiate into osteochondral lineages for application in regenerative medicine .

Heterotopic ossification in lymph node metastasis after rectal cancer resection: a case report and literature review

BackgroundHeterotopic ossification (HO) is the formation of osseous tissue outside the skeleton. HO in malignant tumors of the digestive tract is extremely rare, as is ossification in metastatic lesions from HO-negative digestive tract tumors. Regarding the pathogenesis of HO, two theories have been proposed. The first is that the osteoblastic metaplasia of tumor cells (driven by the epithelial-mesenchymal transition, EMT) results in HO, and the second is that factors secreted by cancer cells lead to the metaplasia of stromal pluripotent cells into osteoblasts. However, the osteogenic mechanisms remain unclear.Case presentationAn 83-year-old Japanese woman underwent low anterior rectal resection for rectal cancer before presentation at our institution, in June 2018. The final diagnosis was stage IIB rectal adenocarcinoma (T4aN0M0). Histological examination did not reveal HO in the primary tumor. Thirteen months after the operation, a solitary metastatic lesion in the brain 20 mm in size and a solitary metastatic lesion in a right axillary lymph node 20 mm in size were diagnosed. The patient was treated with gamma-knife therapy for the brain metastasis. One month later, she was referred to our institution. She underwent lymph node resection. Histological examination revealed that most portions of the affected lymph node were occupied by metastatic tumor cells and that central necrosis and four small ossified lesions without an osteoblast-like cell rim were present in the peripheral region. Immunohistochemical analysis showed tumor cells positive for BMP-2, osteonectin, osteocalcin, AE1/AE3, TGF-β1, Gli2, Smad2/3, and CDX2 and negative for nestin, CD56, and CK7.ConclusionThis is the first English case report of HO in a metachronous metastatic lymph node after the curative resection of HO-negative rectal cancer. Unlike HO lesions in past reports, the HO lesion did not show peripheral osteoblast-like cells, and the immunohistochemical findings indicated that the present case resulted from the EMT.

Osseous mass in a maxillary sinus of an adult male from the 16th–17th-century Spain: Differential diagnosis

ObjectiveTo undertake a differential diagnosis of a large mass found in the left maxillary sinus of a cranium dated to the 16th–17th-century, and to expand knowledge of the diagnosis of osseous tissue formation in osteoarchaeological studies. MaterialA cranium recovered from the cemetery of San Salvador de Palat de Rey church, León (Spain). MethodsMacroscopic analysis, CT scanning. ResultsMacroscopic analysis indicated that the individual was probably a male over 30 years old with an ossified mass in the left maxillary sinus, measuring 24 × 19 × 24 mm, occupying approximately 27 % of the maxillary antrum. Computed tomography revealed a well-demarcated radiolucent unilocular mass with some radiopaque areas, with no communication with the alveoli of the premolars or molars. No erosive lesions or signs of inflammation were found. ConclusionsNeither the macroscopic, nor the radiological characteristics are compatible with inflammatory or malignant pathology, favoring a diagnosis of ossifying fibroma. SignificanceThis case adds to the few reported cases in the osteoarchaeological literature, especially since there is limited relevant reference data to assist diagnosis. The CT scans and 3D reconstruction presented here facilitate differential diagnosis in future paleopathological studies. LimitationsDestructive methods were not authorized. Suggestions for further researchIn the future, micro-CT analysis, which was not performed in the current study, may add new and valuable information.

Effects of Strontium-Doped β-Tricalcium Scaffold on Longitudinal Nuclear Factor-Kappa Beta and Vascular Endothelial Growth Factor Receptor-2 Promoter Activities during Healing in a Murine Critical-Size Bone Defect Model.

It was hypothesized that strontium (Sr)-doped β-tricalcium phosphate (TCP)-based scaffolds have a positive effect on the regeneration of large bone defects (LBD). Readouts in our mice models were nuclear factor-kappa beta (NF-κB) activity and vascular endothelial growth factor receptor-2 (VEGFR-2) promoter activity during the healing process. A 2-mm critical-size femoral fracture was performed in transgenic NF-κB- and VEGFR-2-luciferase reporter mice. The fracture was filled with a 3D-printed β-TCP scaffold with or without Sr. A bioluminescence in-vivo imaging system was used to sequentially investigate NF-κB and VEGFR-2 expression for two months. After sacrifice, soft and osseous tissue formation in the fracture sites was histologically examined. NF-κB activity increased in the β-TCP + Sr group in the latter stage (day 40–60). VEGFR-2 activity increased in the + Sr group from days 0–15 but decreased and showed significantly less activity than the β-TCP and non-scaffold groups from days 40–60. The new bone formation and soft tissue formation in the + Sr group were significantly higher than in the β-TCP group, whereas the percentage of osseous tissue formation in the β-TCP group was significantly higher than in the β-TCP + Sr group. We analyzed longitudinal VEGFR-2 promoter activity and NF-κB activity profiles, as respective agents of angiogenesis and inflammation, during LBD healing. The extended inflammation phase and eventually more rapid resorption of scaffold caused by the addition of strontium accelerates temporary bridging of the fracture gaps. This finding has the potential to inform an improved treatment strategy for patients who suffer from osteoporosis.

In vivo analysis of bone-tissue interface in medical grade titanium and porous titanium with and without cenosphere as space holder

The present study aims at understanding the in vivo behavior of titanium (Ti) foam (with and without addition of cenosphere as space holder) developed by powder metallurgy route which follows compaction at an applied pressure of 100 MPa and sintering at 1100 °C for 4 h. Cenosphere with the particle size 150–212 µm was used as spaceholder and its content was 20 wt%. The porosity content of the titanium foam developed in the present study with and without addition of cenosphere was 40% and 27%, respectively. However, they possess reduced yield strength in compression as compared to medical grade titanium. In vivo study was carried out by implanting the samples in bone defect of rabbit femur. All the titanium based samples were well-integrated within the host bone tissue which is revealed in radiography and micro-CT (µ-CT) images of the implants after three months of insertion. Fluorochrome labeling using oxytetracycline marker showed better and comparable new osseous tissue formation in medical grade Ti and porous Ti with cenosphere as space holder after three months as compared to porous Ti. The scanning electron microscopic image of the bone sample interface showed strong bonding with the signature of marginal bone in-growth inside the tissue. Finally, the in vivo behavior was correlated with initial microstructure and composition of the material. The performance of the titanium foam was evaluated by the detailed analysis of the physicochemical properties and in vivo behavior.

A new standardized critical size bone defect model in the pig forehead for comparative testing of bone regeneration materials

The preclinical study aimed to establish a standardized preclinical model to investigate osseous graft consolidation in defect configurations of limited regenerative capacity. Critical size defects (CSD) were prepared and titanium tubes inserted for defect separation from local bone in the forehead area of 18 pigs. Defects were filled with demineralized bovine bone mineral (DBBM) or served as empty controls and were covered with a resorbable collagen membrane (CM) or left untreated. Six randomly selected pigs were sacrificed after 4, 8 and 12weeks. Specimens were histologically and histomorphometrically analysed focusing on newly formed bone (NFB), demineralized bovine bone mineral (DBBM) and soft tissue (ST) proportions. Four weeks after defect preparation, no statistically significant difference concerning NFB quantity could be detected within the groups. Defects covered with the CM showed lower amounts of DBBM. After 6 and 12weeks, defects augmented with DBBM in combination with a CM (8weeks: 43.12 ± 4.31; 12weeks: 43.05 ± 3.01) showed a statistically significant higher NFB rate compared to empty control defects covered with 8weeks: 7.66 ± 0.59; 12weeks or without a CM; 8weeks: 8.62 ± 2.66; 12weeks: 18.40 ± 2.40. CM application showed no significant impact on osseous defect regeneration or soft tissue formation. Superior NFB could be detected for basal aspect for several evaluation time points. The modification of CSD with titanium tubes represents a suitable model to imitate a one-wall defect regeneration situation. The established model represents a promising method to evaluate graft consolidation in one-wall defect configuration.

Mineralized nanofiber segments coupled with calcium-binding BMP-2 peptides for alveolar bone regeneration

Bone loss around tooth extraction sites can occur, thus making future placement of dental implants difficult. Alveolar bone regeneration can be guided by the application of a nanofibrous bone graft coupled with osteoinductive proteins/peptides, following tooth loss or tooth extraction. In the present study, we demonstrate the potential of mineralized nanofiber segments coupled with calcium-binding bone morphogenetic protein 2 (BMP-2) mimicking peptides for periodontal bone regeneration. Thin electrospun nanofiber membranes of PLGA-collagen-gelatin (2:1:1 wt ratios) were mineralized in 10× modified simulated body fluid (10× mSBF) and cryocut to segments of 20 µm. For predetermined weights of the mineralized nanofiber segments, it was possible to load various amounts of heptaglutamate E7-domain-conjugated BMP-2 peptide. Mineralized short fiber grafts (2 mg), with and without E7-BMP-2 peptides, were implanted into 2 mm × 2 mm (diameter × depth) critical-sized socket defects created in rat maxillae, following extraction of the first molar teeth. A sustained release profile of E7-BMP-2 from the mineralized nanofiber segments was recorded over 4 weeks. X-ray microcomputed tomography (µ-CT) analysis of peptide-loaded nanofiber graft filled defects revealed ∼3 times greater new bone volume and bone mineral density over 4 weeks in comparison to unfilled control defects. Further, histopathology data confirmed the formation of greater new osseous tissue in the BMP2 peptide-loaded, mineralized nanofiber segment group than that of fibrous connective tissue in the unfilled defect group. Altogether, the mineralized nanofiber segments coupled with E7-BMP-2 peptides may be an effective treatment option for alveolar bone loss and defects. Statement of SignificanceWith the high incidence of dental implants/fixtures for missing teeth, the success of the surgical procedures in restorative dentistry is dictated by the quality and quantity of the supporting alveolar bone. To address the problem of alveolar bone loss and defects due to tumor, periodontitis, or even postextraction remodeling, the present study is the first report on the application of mineralized nanofiber fragments coupled with calcium-binding osteoinductive BMP-2 peptides as a synthetic graft material for oral bone regeneration. The ease of fabrication and application of cryocut mineralized nanofiber fragments as maxillofacial bone defect fillers present a promising alternative to the current dental bone graft formulations. Furthermore, the nanofiber segments may also be utilized for several biomedical applications including hemostasis, soft tissue engineering, and wound healing.

Effects of zinc and aprotinin on the healing of ulnar diaphyseal fractures in rabbits

The effects of zinc and aprotinin on fracture healing in experimentally induced fractures were investigated by means of histometric analyses and alkaline phosphatase histochemistry. Healthy 54 adult New Zealand White female rabbits were separated into three groups as control, zinc, and aprotinin treatment. The control animals did not receive any medicament; zinc sulphate was given orally to the rabbits in the Zn group for 15 days. Aprotinin was postoperatively infiltrated into the fracture area at the 3rdand 24thh following operation. Immobilization of fracture ends of all groups was similar throughout the experiment. The zinc administered group displayed the highest alkaline phosphatase positive cell level through the experiment. By day 30 after the operation, fibrocartilage and osseous tissues reached the highest levels in the zinc treated group. Based on the observation of augmented osseous tissue formation and increased alkaline phosphatase positive osteoblastic cell activity in the callus, it was conluded that Zn sulphate is a potent stimulator of bone formation by increasing mineralization in the fractured bone segments.

Polycaprolactone- and polycaprolactone/ceramic-based 3D-bioplotted porous scaffolds for bone regeneration: A comparative study

One of the critical challenges that scaffolding faces in the organ and tissue regeneration field lies in mimicking the structure, and the chemical and biological properties of natural tissue. A high-level control over the architecture, mechanical properties and composition of the materials in contact with cells is essential to overcome such challenge. Therefore, definition of the method, materials and parameters for the production of scaffolds during the fabrication stage is critical. With the recent emergence of rapid prototyping (RP), it is now possible to create three-dimensional (3D) scaffolds with the essential characteristics for the proliferation and regeneration of tissues, such as porosity, mechanical strength, pore size and pore interconnectivity, and biocompatibility.In this study, we employed 3D bioplotting, a RP technology, to fabricate scaffolds made from (i) pure polycaprolactone (PCL) and (ii) a composite based on PCL and ceramic micro-powder. The ceramics used for the composite were bovine bone filling Nukbone® (NKB), and hydroxyapatite (HA) with 5%, 10% or 20% wt. content. The scaffolds were fabricated in a cellular lattice structure (i.e. meshing mode) using a 0/90° lay down pattern with a continuous contour filament in order to achieve interconnected porous reticular structures. We varied the temperature, as well as injection speed and pressure during the bioplotting process to achieve scaffolds with pore size ranging between 200 and 400μm and adequate mechanical stability. The resulting scaffolds had an average pore size of 323μm and an average porosity of 32%.Characterization through ATR-FTIR revealed the presence of the characteristic bands of hydroxyapatite in the PCL matrix, and presented an increase of the intensity of the phosphate and carbonyl bands as the ceramic content increased. The bioplotted 3D scaffolds have a Young's modulus (E) in the range between 0.121 and 0.171GPa, which is compatible with the modulus of natural bone. PCL/NKB scaffolds, particularly 10NKBP (10% NKB wt.) exhibited the highest proliferation optical density, demonstrating an evident osteoconductive effect when cultured in Dulbecco's Modified Eagle Medium (DMEM). Scanning electron microscopy (SEM) confirmed osteoblast anchorage to all composite scaffolds, but a low adhesion to the all-PCL scaffold, as well as cell proliferation. The results from this study demonstrate the potential of PCL/NKB 3D bioplotted scaffolds as viable platforms to enable osseous tissue formation, which can be used in several tissue engineering applications, including improvement of bone tissue regeneration.

Evaluation of the Effect of Platelet-Rich Fibrin on Long Bone Healing: An Experimental Rat Model.

Pseudoarthrosis, or nonunion, of the long bones is a challenging medical condition for orthopedic surgeons to treat. Therefore, healing enhancer materials are commonly used. The authors investigated whether platelet-rich fibrin accelerates long bone healing by comparing radiological and histological findings in a rat model of open femoral fracture. Platelet-rich fibrin is a current biomaterial that contains many growth factors and platelets. There are no studies in the literature investigating the effects of platelet-rich fibrin on fracture healing. Sixteen mature male rats were divided into 2 groups. In both groups, an open femoral fracture was created. The platelet-rich fibrin was obtained by centrifuging blood collected from the rats. Rats in the study group were treated with sterile platelet-rich fibrin, and those in the control group were administered saline. The rats were killed at the end of 4 weeks and examined histologically and radiologically. The radiographic and histological scores of the 2 groups differed significantly (P<.05). These results indicate that platelet-rich fibrin is an efficient biomaterial in fracture healing and that it increases the amount of osseous tissue formation. Platelet-rich fibrin does not cause an allergic reaction, is cost-effective, and is easy to obtain. Additional studies are necessary to determine whether platelet-rich fibrin accelerates the fracture healing process or induces a better quality of fracture healing. [Orthopedics. 2017; 40(3):e479-e484.].

Rapid Prototyping Assisted Scaffold Fabrication for Bone Tissue Regeneration

&lt;p class="1Body"&gt;The review article focuses on Rapid Prototyped assisted scaffold fabrication for bone tissue regeneration, particularly in respect of its mechanical properties and cell culture abilities. The distinct feature of computer aided design and computer aided manufacturing (CAD &amp;amp; CAM), imaging technology and rapid prototyping (RP) technology has been used by different researchers to print porous scaffolds with requisite shape and interconnected channels for osseous tissue formation. This study concludes that the use of RP in scaffold manufacturing offers patient specific designed scaffolds&lt;strong&gt; &lt;/strong&gt;with improved strength, in-vitro and in-vivo cell culture capability unlike traditional scaffold fabrication techniques. Tissue engineering using 3D Printing is a viable substitute for organ transplant, which&lt;strong&gt; &lt;/strong&gt;requires willing donors to part with their organs. This study reviewed the benefits of RP/imaging/CAD-CAM to develop scaffolds for bone&lt;strong&gt; &lt;/strong&gt;tissue regeneration and it serves those patients who could not be accurately treated by traditional means. The article is helpful to study the influence of RP in the field of organ transplant&lt;/p&gt;

Influence of single and binary doping of strontium and lithium on in vivo biological properties of bioactive glass scaffolds

Effects of strontium and lithium ion doping on the biological properties of bioactive glass (BAG) porous scaffolds have been checked in vitro and in vivo. BAG scaffolds were prepared by conventional glass melting route and subsequently, scaffolds were produced by evaporation of fugitive pore formers. After thorough physico-chemical and in vitro cell characterization, scaffolds were used for pre-clinical study. Soft and hard tissue formation in a rabbit femoral defect model after 2 and 4 months, were assessed using different tools. Histological observations showed excellent osseous tissue formation in Sr and Li + Sr scaffolds and moderate bone regeneration in Li scaffolds. Fluorochrome labeling studies showed wide regions of new bone formation in Sr and Li + Sr doped samples as compared to Li doped samples. SEM revealed abundant collagenous network and minimal or no interfacial gap between bone and implant in Sr and Li + Sr doped samples compared to Li doped samples. Micro CT of Li + Sr samples showed highest degree of peripheral cancellous tissue formation on periphery and cortical tissues inside implanted samples and vascularity among four compositions. Our findings suggest that addition of Sr and/or Li alters physico-chemical properties of BAG and promotes early stage in vivo osseointegration and bone remodeling that may offer new insight in bone tissue engineering.

Muscle and Bone: Combating the Evil Side of the Connection.

Muscle and Bone: Combating the Evil Side of the Connection.

Indirect fabrication of hydroxyapatite/β-tricalcium phosphate scaffold for osseous tissue formation using additive manufacturing technology

Patient specific HA/β-TCP scaffold were fabricated using an indirect fabrication approach which involves the application of rapid prototyping technology. β-TCP powder with 10, 20 and 30 % HA concentrations were analyzed for different sintering temperatures. Scaffolds were evaluated by Scanning Electron Microscopy, X-ray diffraction, compression tests, Fourier transform infrared spectroscopy and cytotoxicity tests using human osteosarcoma cell line. Results include HA/β-TCP scaffold porosity, volumetric shrinkage, mechanical properties, bonding, structural phase change and cytotoxicity.

Periosteum-derived micro-grafts for tissue regeneration of human maxillary bone

The bone regeneration is one of the most important challenges for regenerative medicine. In maxillo-facial area, bone resorption of the alveolar crest occurs after tooth extraction and leads to several risks for rehabilitation treatments, including dental implants procedures. Goal of our study was to demonstrate the efficacy of an innovative clinical protocol of bone tissue engineering called Rigenera protocol, aimed to create and optimize bio-complexes constituted by collagen biomaterial and human autologous periosteum-derived micro-grafts. We assessed the capacity of these bio-complexes to prevent the bone resorption in the alveolar crest with respect to simple collagen performing histological evaluations of neo-formed osseous tissue. We demonstrated that autologous bio-complexes significantly reduced the bone resorption of both horizontal and vertical dimension of alveolar crest when compared to collagen alone. We also showed that these bio-complexes accelerate the ossification process triggering the formation of new osseous tissue after 45 days from treatment and increasing the calcified matrix after 60 days and until to 120 days with respect to collagen alone. Taken together, these data showed the efficacy of bio-complexes composed by periosteum-derived micro-grafts and collagen in the alveolar ridge preservation through a reduction of bone resorption and an enhancement of new osseous tissue formation.

Positive effect of tadalafil, a phosphodiesterase-5 inhibitor, on fracture healing in rat femur.

This study aims to investigate whether tadalafil accelerates fracture healing with an efficiency equal to that of sildenafil. Fracture healing was studied using a rat closed femur fracture model. Forty-eight male Wistar albino rats (mean age 13 weeks; range 12 to 14 weeks) were divided into three groups: 16 received sildenafil (5 mg/kg/day per oral), 16 received tadalafil (1 mg/kg/day per oral), and 16 (control group) received saline daily. After two and five weeks, eight rats from each group were euthanized and bone healing was evaluated using radiographic, histologic, and histomorphometric analyses. At second week, radiologic score of tadalafil group was higher than the sildenafil treated groups and the sildenafil and tadalafil groups both had higher radiographic scores than the control group, all groups had similar scores at fifth week. The sildenafil and tadalafil treated group exhibited smaller callus diameter at the second week comparing to control group but the difference was not statistically significant, while callus diameter was significantly smaller in tadalafil group when compared to the control group in fifth week. Compared with the control group, cartilage percentage of the callus was lower in the sildenafil group at two weeks and lower in both the tadalafil and sildenafil groups at five weeks. There were no differences between the tadalafil and sildenafil groups regarding the radiographic scores, callus size, cartilage and osseous callus percentage, and the qualitative bridging scores at second or fifth week. This study demonstrated that tadalafil accelerates fracture healing by enhancing osseous tissue formation similar to sildenafil.