A Current Overview of Materials and Strategies for Potential Use in Maxillofacial Tissue Regeneration

Tissue regeneration is rapidly evolving to treat anomalies in the entire human body. The production of biodegradable, customizable scaffolds to achieve this clinical aim is dependent on the interdisciplinary collaboration among clinicians, bioengineers and materials scientists. While bone grafts and varying reconstructive procedures have been traditionally used for maxillofacial defects, the goal of this review is to provide insight on all materials involved in the progressing utilization of the tissue engineering approach to yield successful treatment outcomes for both hard and soft tissues. In vitro and in vivo studies that have demonstrated the restoration of bone and cartilage tissue with different scaffold material types, stem cells and growth factors show promise in regenerative treatment interventions for maxillofacial defects. The repair of the temporomandibular joint (TMJ) disc and mandibular bone were discussed extensively in the report, supported by evidence of regeneration of the same tissue types in different medical capacities. Furthermore, in addition to the thorough explanation of polymeric, ceramic, and composite scaffolds, this review includes the application of biodegradable metallic scaffolds for regeneration of hard tissue. The purpose of compiling all the relevant information in this review is to lay the foundation for future investigation in materials used in scaffold synthesis in the realm of oral and maxillofacial surgery

Dental Implant Macrogeometry and Biomaterials

Dental implant treatments are widely used and can be an option for lost teeth. Most treatment alternatives are limited due to bone structure, bone density, and patient’s health condition. This book is focused on simple and complicated clinical cases, different types and designs of implants, and also the way to obtain bone-to-implant contact. We have also sought to assess different biomaterials, bone stimulators, and types of dental implants that can reduce the gap, protect the peri-implant bone, and increase the aesthetics. The relationship of bone formation and biomaterials with dental implants is the key factor in bringing back the full reconstruction of soft and hard tissues. Additionally, the type of materials used for implant development are extremely important, especially in relation to strength and bending forces. The contact and protection of bundle bone with both biomaterials and implants will provide highly predictable success in aesthetics and function

Oral Tissues as Source for Bone Regeneration in Dental Implantology

One of the most common problems in Regenerative Medicine is the regeneration of damaged bone with the aim of repairing or replacing lost or damaged bone tissue by stimulating the natural regenerative process. Particularly in the fields of orthopedic, plastic, reconstructive, maxillofacial and craniofacial surgery there is need for successful methods to restore bone. From a regenerative point of view two different bone replacement problems can be distinguished: large bone defects and small bone defects. Currently, no perfect system exists for the treatment of large bone defects

Bone Tissue Engineering: A Literature Review

Introduction: Classic bone tissue engineering involves use of osteogenic cells, growth factors, and bone scaffolds to generate a graft material to replace the gold standard which is autogenous bone graft. Several modifications have been applied to the classic approach but none of them can fully regenerate bone defects. The current study reviewes the literatures in applications of bone tissue engineering both in vivo and in vitro. Materials and Methods: An electronic search in MEDLINE was conducted and both in vivo and in vitro studies were included using bone scaffolds with or without osteogenic growth factors or stem cells. In vitro studies which did not investigate cell-scaffold interactions and in vivo studies which did not measure new bone formation were excluded. Results: Of 86 studies, 38 concerned in vitro and 48 in vivo studies. These studies were divided into six groups based on scaffold which they used: Synthetic, natural, polymers (non-ceramics), composites (polymer+ceramic), metal-based and nano-scaffolds. The results of the studies were compared in a qualitative manner. In vitro studies were mostly conducted on polymers, while relatively more animal and clinical studies were performed on ceramics. The most commonly used scaffolds, stem cells and growth factor were synthetic ceramics, bone marrow stem cells and bone morphgenic protein 2, respectively. Conclusion: Determination of the most successful approach was not possible due to the presence of several variable and variances in analyzing methods and data report. However, studies which used all three components of BTE, including scaffolds, growth factors and stem cells, showed good results both in vitro and in vivo

Clinical Application of Human Mesenchymal Stromal Cells for Bone Tissue Engineering

The gold standard in the repair of bony defects is autologous bone grafting, even though it has drawbacks in terms of availability and morbidity at the harvesting site. Bone-tissue engineering, in which osteogenic cells and scaffolds are combined, is considered as a potential bone graft substitute strategy. Proof-of-principle for bone tissue engineering using mesenchymal stromal cells (MSCs) has been demonstrated in various animal models. In addition, 7 human clinical studies have so far been conducted. Because the experimental design and evaluation parameters of the studies are rather heterogeneous, it is difficult to draw conclusive evidence on the performance of one approach over the other. However, it seems that bone apposition by the grafted MSCs in these studies is observed but not sufficient to bridge large bone defects. In this paper, we discuss the published human clinical studies performed so far for bone-tissue regeneration, using culture-expanded, nongenetically modified MSCs from various sources and extract from it points of consideration for future clinical studies

Autologous stem cells as a promising therapeutic approach for augmentation of alveolar bone

The current gold standard for reconstructive bone surgery is based on autologous bone grafts. However, the risk of complications at both the donor and recipient sites is considerable. There is therefore a need to explore alternative methods of bone regeneration which will restore a defect to full functionality and meet esthetic demands. Nowhere is this a greater challenge than in reconstruction of defects in the orofacial region. Preliminary data, from limited in vitro and in vivo studies, indicate that bone marrow-derived MSC have potential application in bone tissue regeneration. However, interpretation of these studies is complicated by lack of conformity with respect to cell type (expanded or native), culture medium, source of growth factors, expansion time, cell dose and other variables. Moreover, biopsies are required to confirm the osteogenic capacity of the implanted cells and this has not been done routinely. In most studies to date, follow-up has been limited to radiographs, which do not allow differentiation between bone tissue formed by the implanted cells and by the native cells from the border of the osseous defect. The question also remains as to whether the presence of any new bone should qualify as clinical success, or whether a successful outcome requires evidence of new bone formation at the center of the regenerated area. With respect to culture and expansion of MSC for bone tissue engineering, a further issue has arisen, namely the exclusion of animal-derived products from culture medium, requiring a human-derived source of growth factors to replace FBS. The work presented in this thesis was undertaken in order to develop and validate each step in a standardized protocol for expanding autologous MSC in vitro in a GMP-compliant facility (Study II). The expanded MSC produced by this protocol were then applied in a phase I/II clinical trial of restoration of the mandibular alveolar ridge in 11 patients. The surgery was carried out by one experienced oral surgeon (Study III). The same surgeon also undertook the post-operative follow-up, with standardized patient evaluations at each appointment. Bone regeneration was confirmed in all 11 patients, as evidenced by radiographs and biopsies taken at installation of all 21 dental implants. All the implants osseo-integrated. All patients considered the outcomes to be satisfactory, with minimum pain and no morbidity. In a retrospective study of 59 patients who had undergone advanced alveolar ridge reconstruction in accordance with the current gold standard procedure, using autologous bone grafts (Study I), patient satisfaction and OHRQoL among participants was favorable. Despite their overall satisfaction with the outcome, these patients reported significant pain and morbidity. Furthermore, procedures based on autologous grafts from the iliac crest require substantial resources including hospitalization and sick leave. The following conclusions are drawn from this series of studies. Firstly, a standard protocol has been established for GMP expansion of autologous human MSC, using PL as a source of growth factors instead of FBS. Secondly, fresh autologous MSC can be manufactured, expanded and applied in bone regeneration, despite considerable geographic distance between the cell production facility and the clinical center. Thirdly, this protocol was successfully applied for alveolar ridge bone regeneration in 11 patients, with clinical outcomes comparable to those achieved using grafted autologous bone, recovered surgically from a second site. Although patient satisfaction with the new protocol was no different from the standard approach, those treated according to the new protocol reported low pain and morbidity. The results of the comprehensive trial confirm that bone marrow mesenchymal stem cells can successfully promote bone regeneration, with no unexpected adverse events and minimal pain. Hence, this novel augmentation procedure warrants further investigation. It has the potential to form the basis of a new therapeutic approach which may challenge the current gold standard

Differentiation of Human Embryonic Stem Cells into Cells with Corneal Keratocyte Phenotype

Corneal transparency depends on a unique extracellular matrix secreted by stromal keratocytes, mesenchymal cells of neural crest lineage. Derivation of keratocytes from human embryonic stem (hES) cells could elucidate the keratocyte developmental pathway and open a potential for cell-based therapy for corneal blindness. This study seeks to identify conditions inducing differentiation of pluripotent hES cells to the keratocyte lineage. Neural differentiation of hES cell line WA01(H1) was induced by co-culture with mouse PA6 fibroblasts. After 6 days of co-culture, hES cells expressing cell-surface NGFR protein (CD271, p75NTR) were isolated by immunoaffinity adsorption, and cultured as a monolayer for one week. Keratocyte phenotype was induced by substratum-independent pellet culture in serum-free medium containing ascorbate. Gene expression, examined by quantitative RT-PCR, found hES cells co-cultured with PA6 cells for 6 days to upregulate expression of neural crest genes including NGFR, SNAI1, NTRK3, SOX9, and MSX1. Isolated NGFR-expressing cells were free of PA6 feeder cells. After expansion as a monolayer, mRNAs typifying adult stromal stem cells were detected, including BMI1, KIT, NES, NOTCH1, and SIX2. When these cells were cultured as substratum-free pellets keratocyte markers AQP1, B3GNT7, PTDGS, and ALDH3A1 were upregulated. mRNA for keratocan (KERA), a cornea-specific proteoglycan, was upregulated more than 10,000 fold. Culture medium from pellets contained high molecular weight keratocan modified with keratan sulfate, a unique molecular component of corneal stroma. These results show hES cells can be induced to differentiate into keratocytes in vitro. Pluripotent stem cells, therefore, may provide a renewable source of material for development of treatment of corneal stromal opacities. © 2013 Chan et al