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.

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.

Dental problems including cavities, periodontitis, apical periodontitis, and pulpitis are among the most cost-consuming burden for both patients and the health care system all over the world. The pathological consequences of these complications importantly lead to tooth loss causing functional and psychological conflictions for patients. The traditional treatment includes removing the impaired tooth or its restoration using hard restorative materials that are supposed to mimic the tissue of enamel or dentine whereas these materials cannot simulate the chemical, biological, or physical characteristics of a natural tooth. Therefore, different daily-progressing methods of tissue engineering (TE) are being propounded as new and promising approaches for managing dentistry conflicts. TE is now considered almost a practical, reproducible, and clinically safe therapy for regenerating different oral and dental tissues including either the whole dental organ or its various anatomical parts. TE necessarily constitutes three angles of stem cell (SC), scaffold, and essential growth factors (GFs). Generally, scaffolds can be made of decellularized scaffolds (usually containing the extra-cellular matrix (ECM) of target organs and tissues) or biologic scaffolds (containing natural polymer). The current study aims to review the studies conducted in the recent decade on decellularized and biological scaffolds and their potential applications in modern regenerative dentistry.

Decellularized and biological scaffolds in dental and craniofacial tissue engineering: a comprehensive overview

Understanding the biological and morphological reactions of human cells towards different dentinal derivate grafting materials is fundamental for choosing the type of dentin for specific clinical situations. This study aimed to evaluate human periodontal ligament fibroblasts (hPLF) cells exposed to different dentinal derivates particles. The study design included the in vitro evaluation of mineralized dentine (SG), deproteinized and demineralized dentine (DDP), and demineralized dentine (TT) as test materials and of deproteinized bovine bone (BIOS) as the positive control material. The materials were kept with the hPLF cell line, and the evaluations were made after 24 h, 72 h, and 7 days of in vitro culture. The evaluated outcomes were proliferation by using XTT assays, the morphological characteristics by light microscopy (LM) and by the use of scanning electron microscopy (SEM), and adhesion by using confocal microscopy (CLSM). Overall, the experimental materials induced a positive response of the hPLFs in terms of proliferation and adhesion. The XTT assay showed the TT, and the SG induced significant growth compared to the negative control at 7 days follow-up. The morphological data supported the XTT assay: the LM observations showed the presence of densely packed cells with a modified shape; the SEM observations allowed the assessment of how fibroblasts exposed to DDP and TT presented cytoplasmatic extensions; and SG and BIOS also presented the thickening of the cellular membrane. The CLMS observations showed the expression of the proliferative marker, as well as and the expression of cytoskeletal elements involved in the adhesion process. In particular, the vinculin and integrin signals were stronger at 72 h, while the actin signal remained constantly expressed in all the follow-up of the sample exposed to SG material. The integrin signal was stronger at 72 h, and the vinculin and actin signals were stronger at 7 days follow-up in the sample exposed to DDP material. The vinculin and integrin signals were stronger at 72 h follow-up in the sample exposed to TT material; vinculin and integrin signals appear stronger at 24 h follow-up in the sample exposed to BIOS material. These data confirmed how dentinal derivates present satisfying biocompatibility and high conductivity and inductivity properties fundamental in the regenerative processes. Furthermore, the knowledge of the effects of the dentin's degree of mineralization on cellular behavior will help clinicians choose the type of dentine derivates material according to the required clinical situation.

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Bio-Morphological Reaction of Human Periodontal Ligament Fibroblasts to Different Types of Dentinal Derivates: In Vitro Study

Background and Objectives: The aim of the present systematic review and meta-analysis was to investigate the efficacy of leukocyte–platelet-rich fibrin (L-PRF) in addition to coronally advanced flap (CAF) for the treatment of both single and multiple gingival recessions (GRs) compared to the CAF alone and to the adjunct of connective tissue graft (CTG). Root coverage outcomes using platelet concentrates have gained increased interest. In particular, it has been suggested that adding L-PRF to CAF may provide further benefits in the treatment of GRs. Materials and Methods: An electronic and manual literature search was conducted to identify randomized controlled trials (RTCs) investigating root coverage outcomes with CAF + L-PRF. The outcomes of interest included mean root coverage (mRC), recession reduction, keratinized tissue width (KTW) gain, gingival thickness (GT) gain, and patient-reported outcome measures (PROms) such as pain perception and discomfort. Results: A total of 275 patients and 611 surgical sites were analyzed. L-PRF in adjunct to single CAF seems to show statistically significant results regarding clinical attachment level (CAL) with a weighted means (WM) 0.43 95% CI (−0.04, 0.91), p < 0.0001, GT (WM 0.17 95% CI (−0.02, 0.36), p < 0.0001, and mRC (WM 13.95 95% CI (−1.99, 29.88) p < 0.0001, compared to single CAF alone. Interesting results were obtained from the adjunct of PRF to multiple CAF with respect to multiple CAF alone with an increase in the mRC WM 0.07 95% CI (−30.22, 30.35), p = 0.0001, and PPD change WM 0.26 95% CI (−0.06, 0.58), p < 00001. On the other hand, no statistically significant data were obtained when L-PRF was added to single or multiple CAF combined with CTG according to the included outcomes such as mRC (p = 0.03 overall). Conclusions: L-PRF is a valid alternative to CAF alone. L-PRF compared to CTG in single and multiple CAF showed statistically significant results regarding pain perception and discomfort PROms (p < 0.0001). However, CTG remains the gold standard for treating gingival recession.

Platelet-Rich Fibrin in Single and Multiple Coronally Advanced Flap for Type 1 Recession: An Updated Systematic Review and Meta-Analysis.

Soft tissue augmentation at the implant site is one of several techniques suggested in the case of soft and hard tissue deficiency after implant rehabilitation. The gold standard in this procedure is connective tissue graft (CTG), which is considered an autologous material with a high proliferative pattern. Today, several collagen matrices (VCMXs) are on the market as CTG substitutes and are recommended for this type of procedure. The aim of this case report is to compare the resorption process and the volume gain of two potential collagen matrices (VCMXA and VCMXB) of porcine origin for soft tissue augmentation around single implants. 3D analysis with dedicated software (GOM inspect® Braunschweig, Germany) was performed to understand the volumetric and surface changes on the vestibular aspect and the amount of resorbed biomaterial at 7 days from the surgery and at 3 months of follow up. Considering the limitation of the four included patients and the different surgical sites (13 and 17 for VCMXA and 26 and 25 for VCMXB), both VCMXs showed interesting results with respect to the baseline at 7 days (VCMXA gain, + 2.93 ± 1.65 mm; VCMXB, + 2.58 ± 1.11 mm); however, after 3 months of follow up, an important remodelling process was present in both treated sites (VCMXA, + 2.00 ± 0.99 mm; VCMXB, + 0.41 ± 0.73 mm). Soft tissue augmentation at the implant site resulted in a similar increase in volume for both the matrices. On the other hand, VCMXA seemed to preserve more volume at 3 months. Future randomised clinical trials are needed to confirm these results. Page 2 of Mancini et al. Plast Aesthet Res 2021;8:26 https://dx.doi.org/10.20517/2347-9264.2021.25 9

/pdf/3d-analysis-at-implant-sites-after-soft-tissue-augmentation-30g480y7r9.pdf

Adriano Fratini

Papers

Biomaterials for Periodontal and Peri-Implant Regeneration.

Platelet-Rich Fibrin in Single and Multiple Coronally Advanced Flap for Type 1 Recession: An Updated Systematic Review and Meta-Analysis.

3D analysis at implant sites after soft tissue augmentation with two types of collagen matrices: a pilot study