https://www.commed.vcu.edu/Chronic_Disease/2012/cochranrvwrschbias.pdf

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

Conventional bone grafting procedures used to treat bone defects have several limitations. An important aspect of bone tissue engineering is developing novel bone substitute biomaterials for bone grafts to repair orthopedic defects. Considerable attention has been given to chitosan, a natural biopolymer primarily extracted from crustacean shells, which offers desirable characteristics, such as being biocompatible, biodegradable, and osteoconductive. This review presents an overview of the chitosan-based biomaterials for bone tissue engineering (BTE). It covers the basic knowledge of chitosan in terms of biomaterials, the traditional and novel strategies of the chitosan scaffold fabrication process, and their advantages and disadvantages. Furthermore, this paper integrates the relevant contributions in giving a brief insight into the recent research development of chitosan-based scaffolds and their limitations in BTE. The last part of the review discusses the next-generation smart chitosan-based scaffold and current applications in regenerative dentistry and future directions in the field of mineralized tissue regeneration.

Chitosan-Based Scaffold for Mineralized Tissues Regeneration

Dental, oral, and craniofacial (DOC) regenerative medicine aims to repair or regenerate DOC tissues including teeth, dental pulp, periodontal tissues, salivary gland, temporomandibular joint (TMJ), hard (bone, cartilage), and soft (muscle, nerve, skin) tissues of the craniofacial complex. Polymeric materials have a broad range of applications in biomedical engineering and regenerative medicine functioning as tissue engineering scaffolds, carriers for cell-based therapies, and biomedical devices for delivery of drugs and biologics. The focus of this review is to discuss the properties and clinical indications of polymeric scaffold materials and extracellular matrix technologies for DOC regenerative medicine. More specifically, this review outlines the key properties, advantages and drawbacks of natural polymers including alginate, cellulose, chitosan, silk, collagen, gelatin, fibrin, laminin, decellularized extracellular matrix, and hyaluronic acid, as well as synthetic polymers including polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), poly (ethylene glycol) (PEG), and Zwitterionic polymers. This review highlights key clinical applications of polymeric scaffolding materials to repair and/or regenerate various DOC tissues. Particularly, polymeric materials used in clinical procedures are discussed including alveolar ridge preservation, vertical and horizontal ridge augmentation, maxillary sinus augmentation, TMJ reconstruction, periodontal regeneration, periodontal/peri-implant plastic surgery, regenerative endodontics. In addition, polymeric scaffolds application in whole tooth and salivary gland regeneration are discussed.

Polymeric Scaffolds for Dental, Oral, and Craniofacial Regenerative Medicine.

Temporomandibular joint (TMJ) osteoarthritis is a degenerative disease, characterized by gradual cartilage degradation, bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical therapy have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In last years, stem cell-based therapy has collected much attention as a possible approach toward tissue repair and regeneration. Mesenchymal stem cells (MSCs), derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will describe the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ, particularly focusing on the MSC-based therapy and tissue engineering. 

Stem Cells in Temporomandibular Joint Engineering: State of Art and Future Persectives

The aim of this study is to compare cone-beam computed tomography (CBCT) and bi-dimensional reconstructed lateral cephalograms (RLCs) in assessing mandibular body length and growth and to evaluate how mandibular reshaping influences the error in measuring mandibular body growth in bi-dimensional radiographs. Twenty-five patients with two CBCT scans taken at a mean distance of 2.21 ± 0.5 years were selected. The following measurements were performed: right and left mandibular body length at each point in time, mandibular growth, inter-gonial distance and mandibular symphyseal angle. From each CBCT, an RLC was obtained, and mandibular body length and growth were measured. Data analysis revealed a statistically and clinically significant difference in CBCT and RLC regarding the mandibular length of each patient at each point in time. However, mandibular growth was almost identical. A linear regression was performed to predict growth distortion between RLCs and CBCT depending on the ratio between transverse and sagittal mandibular growth. The expected maximum and minimum distortion, however, appeared not to be significant. In fact, a second linear regression model and a Bland–Altman test revealed a strong correlation between measurements of average mandibular body growth by CBCT and RLCs. As the same distortion occurs in the first and second RLCs, bi-dimensional radiographs remain the method of choice in evaluating mandibular body growth.

/pdf/assessing-mandibular-body-changes-in-growing-subjects-a-1zpm2t9omn.pdf

Assessing mandibular body changes in growing subjects: a comparison of CBCT and reconstructed lateral cephalogram measurements.

In periodontitis patients, furcation defects are crucial sites to regenerate due to their complex anatomy. Various modern surgical techniques and use of biomaterials have been suggested in the literature. Among all, platelet-rich fibrin (PRF) has potential in tissue regeneration thanks to its role in the release of growth factors. Therefore, the purpose of this study was to evaluate the beneficial effect of the addition of PRF to open flap debridement (OFD) or as an adjuvant to other biomaterials such as bone grafts in the treatment of grade 2 mandibular furcation defects. Systematic research was carried out on the databases Medline, Scopus, Embase, and Cochrane Library and registered on PROSPERO (CRD42020167662). According to the PICO guidelines by Cochrane, randomized trials and prospective non-randomized trials were evaluated, with a minimum follow-up period of 6 months. The inclusion criteria were the absence of systemic diseases, non-smoking patients, and a population aged from 18 to 65 years. Vertical pocket probing depth (PPD), vertical clinical attachment level (VCAL), and gingival recession (REC) were the primary outcomes. Vertical furcation depth (VFD), and the percentage of bone defect fill (%v-BDF) were considered as secondary outcomes. A meta-analysis of the primary and secondary outcomes was performed. Publication bias was assessed through a funnel plot. Eighty-four articles were initially extracted. Eight randomized clinical trials were analyzed according to the exclusion and inclusion criteria. The Quality assessment instrument (QAI) revealed four articles at low risk of bias, one at moderate, and three at high risk of bias. The metanalysis showed significant data regarding PPD, VCAL, VFD and %v-BDF in the comparison between PRF + OFD vs. OFD alone. The adjunct of PRF to a bone graft showed a significant difference for VCAL and a not statistically significant result for the other involved parameters. In conclusion, the adjunctive use of PRF to OFD seems to enhance the periodontal regeneration in the treatment of grade 2 furcation defects. The combination of PRF and bone graft did not show better clinical results, except for VCAL, although the amount of literature with low risk of bias is scarce. Further well-designed studies to evaluate the combination of these two materials are therefore needed.

Use of Platelet-Rich Fibrin in the Treatment of Grade 2 Furcation Defects: Systematic Review and Meta-Analysis.

The field of regeneration interventions in oral and maxillofacial surgeries still represents a challenge for researchers and clinicians. Understanding the biological and morphological behaviour of human cells towards the materials used for the regeneration surgeries is key to successfully choosing and applying the appropriate biomaterials for specific clinical situations. The aim of the study was the biological and morphological evaluation of autologous platelet concentrate materials obtained with different protocols, in culture with human periodontal ligament fibroblasts (HPLF). The study design included the evaluation of Leukocyte-Platelet-Rich-Fibrin (L-PRF), Concentrated Growth Factors (CGF) and autologous platelet gel (APG) in contact with the HPLF cell line after 24 h, 72 h and 7 days of in vitro culture. Cell proliferation and, therefore, viability were evaluated with XTT assays. The morphological response of the cells was evaluated by light microscopy, scanning electron microscopy and confocal microscopy. The XTT assay showed an interesting response in the growth curve. In particular, the material that gave the best results was the CGF. The morphological data supported the XTT assay, showing the best results for the CGF and L-PRF. In conclusion, all the platelet-derived materials stimulated the onset of the growth of the HPLF cell line, making them promising options for periodontal regeneration interventions.

Evaluation of Different Autologous Platelet Concentrate Biomaterials: Morphological and Biological Comparisons and Considerations

Periodontal and peri-implant regeneration is the technique that aims to restore the damaged tissue around teeth and implants. They are surrounded by a different apparatus, and according to it, the regenerative procedure can differ for both sites. During the last century, several biomaterials and biological mediators were proposed to achieve a complete restoration of the damaged tissues with less invasiveness and a tailored approach. Based on relevant systematic reviews and articles searched on PubMed, Scopus, and Cochrane databases, data regarding different biomaterials were extracted and summarized. Bone grafts of different origin, membranes for guided tissue regeneration, growth factors, and stem cells are currently the foundation of the routinary clinical practice. Moreover, a tailored approach, according to the patient and specific to the involved tooth or implant, is mandatory to achieve a better result and a reduction in patient morbidity and discomfort. The aim of this review is to summarize clinical findings and future developments regarding grafts, membranes, molecules, and emerging therapies. In conclusion, tissue engineering is constantly evolving; moreover, a tailor-made approach for each patient is essential to obtain a reliable result and the combination of several biomaterials is the elective choice in several conditions.

https://www.mdpi.com/1996-1944/14/12/3319/pdf

Biomaterials for Periodontal and Peri-Implant Regeneration.

SARS-CoV-2 propagation in the world has led to rapid growth and an acceleration in the discoveries and publications of various interests. The main focus of a consistent number of studies has been the role of angiotensin-converting enzyme 2 (ACE2) in binding the virus and its role in expression of the inflammatory response after transmission. ACE2 is an enzyme involved in the renin–angiotensin system (RAS), whose key role is to regulate and counter angiotensin-converting enzyme (ACE), reducing the amount of angiotensin II and increasing angiotensin 1–7 (Ang1–7), making it a promising drug target for treating cardiovascular diseases. The classical RAS axis, formed by ACE, angiotensin II (Ang II), and angiotensin receptor type 1 (AT1), activates several cell functions and molecular signalling pathways related to tissue injury and inflammation. In contrast, the RAS axis composed of ACE2, Ang1–7, and Mas receptor (MasR) exerts the opposite effect concerning the inflammatory response and tissue fibrosis. Recent studies have shown the presence of the RAS system in periodontal sites where osteoblasts, fibroblasts, and osteoclasts are involved in bone remodelling, suggesting that the role of ACE2 might have a fundamental function in the under- or overexpression of cytokines such as interleukin-6 (IL-6), interleukin-7 (IL-7), tumour necrosis factor alpha (TNF-α), interleukin-2 (IL-2), interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta (TGF-β), associated with a periodontal disorder, mainly during coinfection with SARS-CoV-2, where ACE2 is underexpressed and cannot form the ACE2–Ang1–7–MasR axis. This renders the patient unresponsive to an inflammatory process, facilitating periodontal loss.

Angiotensin-Converting Enzyme 2 as a Possible Correlation between COVID-19 and Periodontal Disease

Tissue engineering represents a novel approach that aims to exploit the use of biomaterials composed mainly of scaffolds, cells (or grafts), and growth factors capable of restoring a specific tissue. Biomaterials represent the future of dental and oral regeneration due to their biocompatibility and affinity with the receiving site. The aim of this review was to collect results and considerations about a new type of biomaterial based on the use of micrografts in combination with different scaffolds. Micrografts are tissue particles enriched with progenitor cells (PCs), which are defined as descendants of stem cells that can differentiate into specialized cells belonging to the same tissue. PCs in the oral cavity might be extracted from various tissues such as dental pulp, periosteum, or periodontal ligament. Moreover, these cells are easy to isolate through a mechanical process that allows for the filtration of cells with a diameter of 80 μm, in contrast with enzymatic procedures where reagents are used and various culture periods are needed. The aim of this review was to collect data regarding the use of micrografts, developed by a Rigenera® chair-side machine, in oral regeneration evaluating the clinical, histological, and radiographical outcomes. There have been encouraging results for the application of micrografts in bone and periodontal regeneration, but further randomized clinical trials are needed to validate this promising outcome.

Leonardo Mancini

Papers

Use of Platelet-Rich Fibrin in the Treatment of Grade 2 Furcation Defects: Systematic Review and Meta-Analysis.

Evaluation of Different Autologous Platelet Concentrate Biomaterials: Morphological and Biological Comparisons and Considerations

Biomaterials for Periodontal and Peri-Implant Regeneration.

Angiotensin-Converting Enzyme 2 as a Possible Correlation between COVID-19 and Periodontal Disease

Rigenera® Autologous Micrografts in Oral Regeneration: Clinical, Histological, and Radiographical Evaluations