Bone Regeneration In Conjunction Research Articles

3D-Printed conductive polymeric scaffolds with direct current electrical stimulation for enhanced bone regeneration.

Various methods have been used to treat bone defects caused by genetic disorders, injury, or disease. Yet, there is still great need to develop alternative approaches to repair damaged bone tissue. Bones naturally exhibit piezoelectric potential, or the ability to convert mechanical stresses into electrical impulses. This phenomenon has been utilized clinically to enhance bone regeneration in conjunction with electrical stimulation (ES) therapies; however, oftentimes with critical-sized bone defects, the bioelectric potential at the site of injury is compromised, resulting in less desirable outcomes. In the present study, the potential of a 3D-printed conductive polymer blend to enhance bone formation through restoration of the bioelectrical microenvironment was evaluated. A commercially available 3D printer was used to create circular, thin-film scaffolds consisting of either polylactide (PLA) or a conductive PLA (CPLA) composite. Preosteoblast cells were seeded onto the scaffolds and subjected to direct current ES via a purpose-built cell culture chamber. It was found that CPLA scaffolds had no adverse effects on cell viability, proliferation or differentiation when compared with control scaffolds. The addition of ES, however, resulted in a significant increase in the expression of osteocalcin, a protein indicative of osteoblast maturation, after 14 days of culture. Furthermore, xylenol orange staining also showed the presence of increased mineralized calcium nodules in cultures undergoing stimulation. This study demonstrates the potential for low-cost, conductive scaffolding materials to support cell viability and enhance in vitro mineralization in conjunction with ES.

Bioactive Glasses as Carriers of Cancer-Targeted Drugs: Challenges and Opportunities in Bone Cancer Treatment.

The treatment of bone cancer involves tumor resection followed by bone reconstruction of the defect caused by the tumor using biomaterials. Additionally, post-surgery protocols cover chemotherapy, radiotherapy, or drug administration, which are employed as adjuvant treatments to prevent tumor recurrence. In this work, we reviewed new strategies for bone cancer treatment based on bioactive glasses as carriers of cancer-targeted and other drugs that are intended for bone regeneration in conjunction with adjuvant treatments. Drugs used in combination with bioactive glasses can be classified into cancer-target, osteoclast-target, and new therapies (such as gene delivery and bioinorganic). Microparticulated, nanoparticulated, or mesoporous bioactive glasses have been used as drug-delivery systems. Additionally, surface modification through functionalization or the production of composites based on polymers and hydrogels has been employed to improve drug-release kinetics. Overall, although different drugs and drug delivery systems have been developed, there is still room for new studies involving kinase inhibitors or antibody-conjugated drugs, as these drugs have been poorly explored in combination with bioactive glasses.

Management of Root Fenestration Using Buccal Decortication and Guided Tissue Regeneration: A Case Report and 3-dimensional Analysis

The management of patients with apical fenestration and clinical symptoms has always been limited to apical root resection and placement of the root tip within the bony crypt. This result would often present resolution of clinical symptoms based on a few case studies. In this case report, we present a case in which apical resection alone did not resolve the patient’s discomfort; on the contrary, it resulted in further bone loss and persistence of clinical symptoms. A corrective surgery was performed with the use of guided bone regeneration in conjunction with decortication of the cortical plate to induce bleeding. The patient symptoms resolved within a few weeks after the surgery, and the follow-up scan showed apical root coverage. Three-dimensional analysis was performed to compare the bony changes between the 2 surgeries and showed a significant amount of bone gain of around 200 mm3 and a 2-mm linear bone gain opposite the distobuccal root. The case presents a conservative approach to manage root fenestration of the buccal plate without further compromising the root apex.

Sustained release of small molecules from carbon nanotube-reinforced monetite calcium phosphate cement

The interest in developing calcium phosphate cement (CPC) as a drug delivery system has risen because of its capability to achieve local and controlled treatment to the site of the bone disease. The purpose of this study was to investigate the release pattern of drug-carrying carboxylic acid-functionalized multi-walled carbon nanotube (MWCNT)-reinforced monetite (DCPA, CaHPO4)-based CPC. Z-Leu-Leu-Leu-al (MG132), a small peptide molecule inhibiting NF-κB-mediated osteoclastic resorption, was used as a model drug. MG132 was added into the cement during setting and released into the medium used to culture indicator cells. Significant cell death was observed in osteoblast MC3T3-E1 cells cultured in the medium incubated with MG132-loaded CPC; however, with the presence of MWCNTs in the cement, the toxic effect was not detectable. NF-κB activation was quantified using a NF-κB promoter-driving luciferase reporter in human embryonic kidney 293 cells. The medium collected after incubation with drug-incorporated CPC with or without MWCNT inhibited TNFα-induced NF-κB activation indicating that the effective amount of MG132 was released. CPC/drug complex showed a rapid release within 24h whereas incorporation of MWCNTs attenuated this burst release effect. In addition, suppression of TNFα-induced osteoclast differentiation in RAW 264.7 cell culture also confirmed the sustained release of MWCNT/CPC/drug. Our data demonstrated the drug delivery capability of this cement composite, which can potentially be used to carry therapeutic molecules to improve bone regeneration in conjunction with its fracture stabilizing function. Furthermore, it suggested a novel approach to lessen the burst release effect of the CPC-based drug delivery system by incorporating functionalized MWCNTs.

Prognostic factors for alveolar regeneration: effect of tissue occlusion on alveolar bone regeneration with guided tissue regeneration.

Design criteria for guided tissue regeneration (GTR) devices include biocompatibility, cell occlusion, space-provision, tissue integration, and ease of use. The objective of this study was to evaluate the effect of cell occlusion and space-provision on alveolar bone regeneration in conjunction with GTR. Routine, critical-size, 6 mm, supra-alveolar, periodontal defects were created in 6 young adult Beagle dogs. Space-providing ePTFE devices, with or without 300-microm laser-drilled pores were implanted to provide for GTR. Treatments were alternated between left and right jaw quadrants in subsequent animals. The gingival flaps were advanced for primary intention healing. The animals were euthanized at week 8 post surgery. The histometric analysis assessed regeneration of alveolar bone relative to space-provision by the ePTFE device. A significant relationship was observed between bone regeneration and space-provision for defect sites receiving the occlusive (beta = 0.194; p < 0.02) and porous (beta = 0.229; p < 0.0004) GTR devices irrespective of treatment (p = 0.14). The bivariate analysis showed that both space-provision and device occlusivity significantly enhanced bone regeneration. Hence, sites receiving the occlusive GTR device and sites with enhanced space-provision showed significantly greater bone regeneration compared to sites receiving the porous GTR device (p = 0.03) or more limited space-provision (p = 0.0002). Cell occlusion and space-provision may significantly influence the magnitude of alveolar bone regeneration in conjunction with guided tissue regeneration.

Prognostic factors for alveolar regeneration: effect of a space-providing biomaterial on guided tissue regeneration.

There is a limited understanding of the effect of bone biomaterials on the healing potential when used in conjunction with guided tissue regeneration (GTR). The objective of this study was to evaluate the effect of a space-providing coral-derived biomaterial on alveolar bone regeneration in conjunction with GTR. Bilateral, critical-size, 6-mm, supra-alveolar, periodontal defects were created in four young adult Beagle dogs. In a split-mouth design, the animals received an ePTFE device to provide for GTR in contralateral defect sites with or without the coral biomaterial. The animals were euthanized at 4 weeks post surgery. A histometric analysis assessed vertical regeneration of alveolar bone relative to space-provision by the ePTFE device. Because of the correlation of within-dog measurements, a mixed model ANOVA was used to analyze the data. There was significantly greater mean bone regeneration in sites receiving calcium carbonate coral implant GTR (cGTR) compared to GTR (p < 0.0001). Sites providing larger wound areas exhibited greater bone regeneration compared to sites exhibiting smaller wound areas (p < 0.0001). However, grouping the sites by wound area thresholds showed that bone regeneration was not significantly different in sites receiving cGTR compared to sites receiving GTR alone, irrespective of the size of the wound area (p > 0.5). Space-provision has a significant effect on bone regeneration following GTR. The coral biomaterial effectively enhances space-provision, and this appears to be the principal mechanism by which this biomaterial supports bone regeneration rather than postulated osteoconductive properties.

Efficacy of high-density versus semipermeable PTFE membranes in an elderly experimental model.

The clinical effectiveness of expanded polytetrafluoroethylene (PTFE) membranes for guided bone regeneration has been reported in the literature on several occasions. However, one major drawback of this material is the need for a second surgical operation for removal of the membrane. In addition, most studies involving guided bone regeneration in animal models have used young animals or animals of unspecified age, but in some clinical situations guided bone regeneration may be indicated in elderly jaw bones. The objectives of this investigation were (1) to evaluate the effectiveness of a newly introduced high-density PTFE membrane (TefGen-FD)-a material that does not require second-stage surgery for its removal-for enhancement of bone ingrowth in elderly rabbits' calvaria and (2) to compare the findings with those obtained with the commonly used semipermeable expanded PTFE membrane (Gore-Tex). Eighteen elderly rabbits (each more than 30 months old) served as the experimental animals in this study. Two non-self-healing, full-thickness defects were created in each rabbit calvarium. One of the 2 defects was fully covered with macroprous expanded PTFE membrane (Gore-Tex); the other defect was covered with microporous PTFE membrane (TefGen-FD). Specimens were obtained at 4, 8, and 16 weeks and examined by means of light microscopy. Clinically, the high-density TefGen membrane was much easier to detach from the underlying bone than was the semipermeable Gore-Tex membrane, which showed strict adherence to bone surface on removal. Microscopically, the Gore-Tex membrane lamellae were infiltrated by fibro-osseous tissue at the membrane's lower surface. A relatively greater speed and quantity of bone regeneration were observed in the defective cavities covered with Gore-Tex membrane than in those covered with TefGen membrane. It appears that the semipermeable Gore-Tex membrane is more effective than the high-density TefGen-FD membrane with respect to guided bone regeneration in elderly bone. These findings have relevance for the clinical situation of using guided bone regeneration in conjunction with implant placement and ridge augmentation procedures in atrophic elderly jaws.

Histological morphology of the e-PTFE/tissue interface in humans subjected to guided bone regeneration in conjunction with oral implant treatment.

The purpose of the present investigation was to study the histological morphology of the e-PTFE membrane/tissue interface in 5 humans subjected to GBR treatment in conjunction with oral implant treatment. Oral implants (Brånemark System) were inserted in extraction sockets 1 to 2 months after extraction of periodontally diseased teeth. The implants were placed approximately 2 mm below the surrounding bone margins. Specially designed 3 mm high cover-screws with horizontal slits for tissue ingrowth were applied to the implants and covered with e-PTFE membranes (GoreTex Augmentation Material). Re-entry was made 7 months later, except in 1 case where the membrane was removed 1 month postoperatively due to exposure and infection. In the remaining 4 sites, circular biopsies comprising membranes, tissues and cover-screws were retrieved. The specimens were fixated, processed and sectioned for light- and transmission electron microscopy. The space between the membrane and the cover-screw was occupied by fibrous tissue and varying amounts of bone. A cell- and vessel-rich fibrous tissue separated the bone from the membrane in the majority of the specimens. The membrane itself was penetrated by fibrous tissue. Fibroblasts and macrophages were the main cell types found in the fibrous tissue. The presence of irregularly shaped cells and unevenly distributed collagen fibres, indicated that the absence of bone formation may be due either to micromovements in the e-PTFE/tissue interface or to formation of fibrous tissue underneath the membrane by penetrating fibroblasts or a combination of these 2 phenomena.