Application of a BMP2-binding heparan sulphate to promote periodontal regeneration

Periodontitis is the most common inflammatory disease that leads to periodontal defects and tooth loss. Regeneration of alveolar bone and soft tissue in periodontal defects is highly desirable but remains challenging. A heparan sulphate variant (HS3) with enhanced affinity for bone morphogenetic protein-2 (BMP2) that, when combined with collagen or ceramic biomaterials, enhances bone tissue regeneration in the axial and cranial skeleton in several animal models was reported previously. In the current study, establishing the efficacy of a collagen/HS3 device for the regeneration of alveolar bone and the adjacent periodontal apparatus and related structures was sought. Collagen sponges loaded with phosphate-buffered saline, HS3, BMP2, or HS3 + BMP2 were implanted into surgically-created intra-bony periodontal defects in rat maxillae. At the 6 week end- point the maxillae were decalcified, and the extent of tissue regeneration determined by histomorphometrical analysis. The combination of collagen/HS3, collagen/BMP2 or collagen/HS3 + BMP2 resulted in a three to four-fold increase in bone regeneration and up to a 1.5 × improvement in functional ligament restoration compared to collagen alone. Moreover, the combination of collagen/HS3 + BMP2 improved the alveolar bone height and reduced the amount of epithelial growth in the apical direction. The implantation of a collagen/ HS3 combination device enhanced the regeneration of alveolar bone and associated periodontal tissues at amounts comparable to collagen in combination with the osteogenic factor BMP2. This study highlights the efficacy of a collagen/HS3 combination device for periodontal regeneration that warrants further development as a point-of-care treatment for periodontitis-related bone and soft tissue loss.

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Surgical-prosthetic treatment of large mandibular cysts

Vojnosanitetski pregled ◽

10.2298/vsp0303365d ◽

2003 ◽

Vol 60 (3) ◽

pp. 365-368

Author(s):

Ljubisa Dzambas ◽

Asen Dzolev

Keyword(s):

Quality Of Life ◽

Soft Tissue ◽

Bone Defect ◽

Tissue Regeneration ◽

Disease Patient ◽

Daily Activities ◽

Bone Tissue Regeneration ◽

Tissue Loss ◽

Mandibular Bone

This paper presents a combined surgical-prosthetic procedure of reconstructing mandibular bone defect in a 53 year old patient, following enucleation of a mandibular cyst (Cystectomy Partsch II). After a thorough diagnostic evaluation, a surgical procedure was planned with the particular attention to the nature of the disease, patient?s condition, size and extension of the cyst, tissue loss, and the possibilities of prosthetic management of a mandibular bone defect with partial postresection dental prosthesis. It is of great importance to point to the significance of teamwork of a maxillofacial surgeon and a specialist in prosthodontics. This kind of cooperation provided very effective and less risky soft tissue, as well as bone tissue regeneration (osteogenesis). The patient?s recovery was fast, and he could return to his daily activities and work without significant changes regarding quality of life after surgery and prosthetic treatment.

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Tooth-Supporting Hard Tissue Regeneration Using Biopolymeric Material Fabrication Strategies

Molecules ◽

10.3390/molecules25204802 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4802

Author(s):

Min Guk Kim ◽

Chan Ho Park

Keyword(s):

Tissue Engineering ◽

Tissue Regeneration ◽

Alveolar Bone ◽

Critical Role ◽

Periodontal Regeneration ◽

Tissue Formation ◽

Hard Tissue ◽

Periodontal Tissues ◽

Mineralized Tissues ◽

Biomechanical Forces

The mineralized tissues (alveolar bone and cementum) are the major components of periodontal tissues and play a critical role to anchor periodontal ligament (PDL) to tooth-root surfaces. The integrated multiple tissues could generate biological or physiological responses to transmitted biomechanical forces by mastication or occlusion. However, due to periodontitis or traumatic injuries, affect destruction or progressive damage of periodontal hard tissues including PDL could be affected and consequently lead to tooth loss. Conventional tissue engineering approaches have been developed to regenerate or repair periodontium but, engineered periodontal tissue formation is still challenging because there are still limitations to control spatial compartmentalization for individual tissues and provide optimal 3D constructs for tooth-supporting tissue regeneration and maturation. Here, we present the recently developed strategies to induce osteogenesis and cementogenesis by the fabrication of 3D architectures or the chemical modifications of biopolymeric materials. These techniques in tooth-supporting hard tissue engineering are highly promising to promote the periodontal regeneration and advance the interfacial tissue formation for tissue integrations of PDL fibrous connective tissue bundles (alveolar bone-to-PDL or PDL-to-cementum) for functioning restorations of the periodontal complex.

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Successful Application of a Galanin-Coated Scaffold for Periodontal Regeneration

Journal of Dental Research ◽

10.1177/00220345211028852 ◽

2021 ◽

pp. 002203452110288

Author(s):

W. Ma ◽

H. Lyu ◽

M. Pandya ◽

G. Gopinathan ◽

X. Luan ◽

...

Keyword(s):

Small Molecule ◽

Tissue Regeneration ◽

Periodontal Regeneration ◽

Tissue Loss ◽

Bioreactor Culture ◽

Subcutaneous Implantation ◽

Alizarin Red ◽

Coating Agent ◽

Periodontal Tissues ◽

Novel Scaffold

The nervous system exerts finely tuned control over all aspects of the life of an organism, including pain, sensation, growth, and development. Recent developments in tissue regeneration research have increasingly turned to small molecule peptides to tailor and augment the biological response following tissue loss or injury. In the present study, we have introduced the small molecule peptide galanin (GAL) as a novel scaffold-coating agent for the healing and regeneration of craniofacial tissues. Using immunohistochemistry, we detected GAL and GAL receptors in healthy periodontal tissues and in the proximity of blood vessels, while exposure to our periodontal disease regimen resulted in a downregulation of GAL. In a 3-dimensional bioreactor culture, GAL coating of collagen scaffolds promoted cell proliferation and matrix synthesis. Following subcutaneous implantation, GAL-coated scaffolds were associated with mineralized bone-like tissue deposits, which reacted positively for alizarin red and von Kossa, and demonstrated increased expression and protein levels of RUNX2, OCN, OSX, and iBSP. In contrast, the GAL receptor antagonist galantide blocked the effect of GAL on Runx2 expression and inhibited mineralization in our subcutaneous implantation model. Moreover, GAL coating promoted periodontal regeneration and a rescue of the periodontal defect generated in our periodontitis model mice. Together, these data demonstrate the efficacy of the neuropeptide GAL as a coating material for tissue regeneration. They are also suggestive of a novel role for neurogenic signaling pathways in craniofacial and periodontal regeneration.

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Regeneration of Periodontal Tissues in Non-human Primates with rhGDF-5 and Beta-Tricalcium Phosphate

Journal of Dental Research ◽

10.1177/0022034511423665 ◽

2011 ◽

Vol 90 (12) ◽

pp. 1416-1421 ◽

Cited By ~ 40

Author(s):

K.B. Emerton ◽

S.J. Drapeau ◽

H. Prasad ◽

M. Rohrer ◽

P. Roffe ◽

...

Keyword(s):

Tissue Regeneration ◽

Tricalcium Phosphate ◽

Alveolar Bone ◽

Periodontal Regeneration ◽

Human Growth ◽

Graft Material ◽

Periodontal Tissue ◽

Periodontal Tissues ◽

Beta Tricalcium Phosphate ◽

Periodontal Tissue Regeneration

The application of growth factors has been advocated in support of periodontal regeneration. Recombinant human growth and differentiation factor-5 (rhGDF-5), a member of the bone morphogenetic protein family, has been used to encourage periodontal tissue regeneration. This study evaluated the dose response of rhGDF-5 lyophilized onto beta-tricalcium phosphate (bTCP) granules for periodontal tissue regeneration in a baboon model. Periodontal defects were created bilaterally in 12 baboons by a split-mouth design. Plaque was allowed to accumulate around wire ligatures to create chronic disease. After 2 mos, the ligatures were removed, and a notch was placed at the base of the defect. Two teeth on each side of the mouth were randomly treated with bTCP only, 0.5, 1.0, or 2.0 mg rhGDF-5/g bTCP. Animals were sacrificed 5 mos post-treatment, with micro-CT and histomorphometric analysis performed. After 5 mos, analysis showed alveolar bone, cementum, and periodontal ligament formation in all treatment groups, with a dose-dependent increase in rhGDF-5-treated groups. Height of periodontal tissues also increased with the addition of rhGDF-5, and the amount of residual graft material decreased with rhGDF-5 treatment. Therefore, rhGDF-5 delivered on bTCP demonstrated effective regeneration of all 3 tissues critical for periodontal repair.

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Regenereation in periodontics

Global Dentistry ◽

10.36879/gsl.dcr.2018.00009 ◽

2018 ◽

Author(s):

Murtaza Kaderi ◽

Mohsin Ali ◽

Alfiya Ali ◽

Tasneem Kaderi

Keyword(s):

Tissue Engineering ◽

Clinical Practice ◽

Periodontal Disease ◽

Disease Progression ◽

Tissue Regeneration ◽

Surgical Procedures ◽

Periodontal Regeneration ◽

Guided Tissue Regeneration ◽

Periodontal Tissues ◽

Extensive Documentation

The goals of periodontal therapy are to arrest of periodontal disease progression and to attain the regeneration of the periodontal apparatus. Osseous grafting and Guided tissue regeneration (GTR) are the two techniques with the most extensive documentation of periodontal regeneration. However, these techniques offer limited potential towards regenerating the periodontal tissues. Recent surgical procedures and application of newer materials aim at greater and more predictable regeneration with the concept of tissue engineering for enhanced periodontal regeneration and functional attachment have been developed, analyzed, and employed in clinical practice

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Platelet-Rich Fibrin Promotes Periodontal Regeneration and Enhances Alveolar Bone Augmentation

BioMed Research International ◽

10.1155/2013/638043 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 20

Author(s):

Qi Li ◽

Shuang Pan ◽

Smit J. Dangaria ◽

Gokul Gopinathan ◽

Antonia Kolokythas ◽

...

Keyword(s):

Tissue Regeneration ◽

Alveolar Bone ◽

Periodontal Regeneration ◽

Principal Component ◽

Nodule Formation ◽

Bone Augmentation ◽

Pilot Studies ◽

Platelet Rich Fibrin ◽

Lineage Differentiation ◽

Osteogenic Lineage

In the present study we have determined the suitability of platelet-rich fibrin (PRF) as a complex scaffold for periodontal tissue regeneration. Replacing PRF with its major component fibrin increased mineralization in alveolar bone progenitors when compared to periodontal progenitors, suggesting that fibrin played a substantial role in PRF-induced osteogenic lineage differentiation. Moreover, there was a 3.6-fold increase in the early osteoblast transcription factor RUNX2 and a 3.1-fold reduction of the mineralization inhibitor MGP as a result of PRF application in alveolar bone progenitors, a trend not observed in periodontal progenitors. Subcutaneous implantation studies revealed that PRF readily integrated with surrounding tissues and was partially replaced with collagen fibers 2 weeks after implantation. Finally, clinical pilot studies in human patients documented an approximately 5 mm elevation of alveolar bone height in tandem with oral mucosal wound healing. Together, these studies suggest that PRF enhances osteogenic lineage differentiation of alveolar bone progenitors more than of periodontal progenitors by augmenting osteoblast differentiation, RUNX2 expression, and mineralized nodule formation via its principal component fibrin. They also document that PRF functions as a complex regenerative scaffold promoting both tissue-specific alveolar bone augmentation and surrounding periodontal soft tissue regeneration via progenitor-specific mechanisms.

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Current Stage of Marine Ceramic Grafts for 3D Bone Tissue Regeneration

Marine Drugs ◽

10.3390/md17080471 ◽

2019 ◽

Vol 17 (8) ◽

pp. 471 ◽

Cited By ~ 5

Author(s):

Patricia Diaz-Rodriguez ◽

Miriam López-Álvarez ◽

Julia Serra ◽

Pío González ◽

Mariana Landín

Keyword(s):

Bone Tissue ◽

Tissue Regeneration ◽

Alveolar Bone ◽

3D Cell Culture ◽

Spinal Fractures ◽

Bone Grafts ◽

Bone Tissue Regeneration ◽

Marine Origin ◽

Age Related ◽

Current Stage

Bioceramic scaffolds are crucial in tissue engineering for bone regeneration. They usually provide hierarchical porosity, bioactivity, and mechanical support supplying osteoconductive properties and allowing for 3D cell culture. In the case of age-related diseases such as osteoarthritis and osteoporosis, or other bone alterations as alveolar bone resorption or spinal fractures, functional tissue recovery usually requires the use of grafts. These bone grafts or bone void fillers are usually based on porous calcium phosphate grains which, once disposed into the bone defect, act as scaffolds by incorporating, to their own porosity, the intergranular one. Despite their routine use in traumatology and dental applications, specific graft requirements such as osteoinductivity or balanced dissolution rate are still not completely fulfilled. Marine origin bioceramics research opens the possibility to find new sources of bone grafts given the wide diversity of marine materials still largely unexplored. The interest in this field has also been urged by the limitations of synthetic or mammalian-derived grafts already in use and broadly investigated. The present review covers the current stage of major marine origin bioceramic grafts for bone tissue regeneration and their promising properties. Both products already available on the market and those in preclinical phases are included. To understand their clear contribution to the field, the main clinical requirements and the current available biological-derived ceramic grafts with their advantages and limitations have been collected.

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Periodontal Bone-Ligament-Cementum Regeneration via Scaffolds and Stem Cells

Cells ◽

10.3390/cells8060537 ◽

2019 ◽

Vol 8 (6) ◽

pp. 537 ◽

Cited By ~ 25

Author(s):

Jin Liu ◽

Jianping Ruan ◽

Michael D. Weir ◽

Ke Ren ◽

Abraham Schneider ◽

...

Keyword(s):

Stem Cells ◽

Gene Therapy ◽

Tooth Loss ◽

Soft Tissues ◽

Alveolar Bone ◽

Periodontal Regeneration ◽

Periodontal Tissues ◽

Oral And Maxillofacial Region ◽

And Function ◽

Bone Remains

Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal ligament (PDL) fibers, and bone. The regeneration of these three types of tissues, including the re-formation of the oriented PDL fibers to be attached firmly to the new cementum and alveolar bone, remains a major challenge. This article represents the first systematic review on the cutting-edge researches on the regeneration of all three types of periodontal tissues and the simultaneous regeneration of the entire bone-PDL-cementum complex, via stem cells, bio-printing, gene therapy, and layered bio-mimetic technologies. This article primarily includes bone regeneration; PDL regeneration; cementum regeneration; endogenous cell-homing and host-mobilized stem cells; 3D bio-printing and generation of the oriented PDL fibers; gene therapy-based approaches for periodontal regeneration; regenerating the bone-PDL-cementum complex via layered materials and cells. These novel developments in stem cell technology and bioactive and bio-mimetic scaffolds are highly promising to substantially enhance the periodontal regeneration including both hard and soft tissues, with applicability to other therapies in the oral and maxillofacial region.

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Local Injection of Allogeneic Stem Cells from Apical Papilla Enhanced Periodontal Tissue Regeneration in Minipig Model of Periodontitis

BioMed Research International ◽

10.1155/2018/3960798 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Guoqing Li ◽

Nannan Han ◽

Xiuli Zhang ◽

Haoqing Yang ◽

Yangyang Cao ◽

...

Keyword(s):

Stem Cells ◽

Tissue Regeneration ◽

Alveolar Bone ◽

Local Injection ◽

Swine Model ◽

Periodontal Tissue ◽

Clinical Assessments ◽

Periodontal Tissues ◽

Periodontal Tissue Regeneration ◽

Apical Papilla

Background. Discovering suitable seeding cells and simple application technique will be beneficial for MSC-mediated treatment of periodontitis. Stem cells from apical papilla (SCAPs) might be the candidate seeding cell for the periodontal tissues regeneration based on their origin and characters. In this research, we investigated the effect of SCAPs on periodontal tissue regeneration in swine by local injection. Methods. We established experimental periodontitis model in miniature pigs and then treated them with SCAPs by local injection. Clinical assessments, computed tomography (CT) scanning, histologic examination, and quantitative measurements were used to evaluate the effect of periodontal tissues regeneration. Results. At 12 weeks after injection, clinical assessments showed that probing depth, gingival recession, and attachment loss values were 5.44±0.77 mm versus 7.33±1.0 mm (p<0.01), 2.33±0.33 mm versus 2.11±0.69 mm (p>0.05), and 7.78±0.84 mm versus 9.44±1.07 mm (p<0.01) in SCAPs group and 0.9% NaCl group, respectively. CT scan results showed a significant increase of 12.86 mm3 alveolar bone regeneration in SCAPs group compared with 0.9% NaCl group. In addition, histopathology results demonstrated remarkable regeneration in SCAPs group, whereas regeneration of periodontal tissue was hardly found in 0.9% NaCl group. Conclusion. Local injection of SCAPs could effectively restore tissue defects brought about by periodontitis in the swine model. Thus, SCAPs, as an easily accessible dental-deriving stem cell, may serve as an alternative application for periodontitis treatment.

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Bioactive Synthetic Peptides for Oral Tissues Regeneration

Frontiers in Materials ◽

10.3389/fmats.2021.655495 ◽

2021 ◽

Vol 8 ◽

Author(s):

Mercedes Bermúdez ◽

Lía Hoz ◽

Gonzalo Montoya ◽

Mikado Nidome ◽

Adriana Pérez-Soria ◽

...

Keyword(s):

Tissue Regeneration ◽

Synthetic Peptides ◽

Alveolar Bone ◽

Biological Effects ◽

The Body ◽

Bioactive Molecules ◽

Tissue Loss ◽

Complex Nature ◽

Major Health Problem

Regenerative therapy in oral tissues has gained relevance since tissue loss due to congenital or acquired diseases as well as trauma is a major health problem worldwide. Regeneration depends on the natural capacity of the body and the use of biomaterials and bioactive molecules that can module the processes to replace lost or damaged tissues and restore function. The combined use of scaffolds, cells, and bioactive molecules such as peptides is considered the best approach to achieve tissue regeneration. These peptides can induce diverse cellular processes as they can influence cell behavior and also can modify scaffold properties, giving as a result the enhancement of cell adhesion, proliferation, migration, differentiation, and biomineralization that are required given the complex nature of oral tissues. Specifically, synthetic peptides (SP) have a positive influence on scaffold biocompatibility since in many cases they can mimic the function of a natural peptide or a full-length protein. Besides, they are bioactive molecules easy to produce, process, and modify, and they can be prepared under well-defined and controlled conditions. This review aims to compile the most relevant information regarding advances in SP for dental and periodontal tissue regeneration, their biological effects, and their clinical implications. Even though most of the SP are still under investigation, some of them have been studied in vitro and in vivo with promising results that may lead to preclinical studies. Besides there are SP that have shown their efficacy in clinical trials such as P11-4 for enamel regeneration or caries prevention and ABM/P-15 for cementum, periodontal ligament (PDL), and alveolar bone on a previously calculus- and biofilm-contaminated zone. Also, some SP are commercially available such as PTH1-34 and PepGen P-15 which are used for bone defects treatment.

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