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This review provides an overview of various materials used in dentistry and oral and maxillofacial surgeries to replace or repair bone defects. The choice of material depends on factors such as tissue viability, size, shape, and defect volume. While small bone defects can regenerate naturally, extensive defects or loss or pathological fractures require surgical intervention and the use of substitute bones. Autologous bone, taken from the patient’s own body, is the gold standard for bone grafting but has drawbacks such as uncertain prognosis, surgery at the donor site, and limited availability. Other alternatives for medium and small-sized defects include allografts (from human donors), xenografts (from animals), and synthetic materials with osteoconductive properties. Allografts are carefully selected and processed human bone materials, while xenografts are derived from animals and possess similar chemical composition to human bone. Synthetic materials such as ceramics and bioactive glasses are used for small defects but may lack osteoinductivity and moldability. Calcium-phosphate-based ceramics, particularly hydroxyapatite, are extensively studied and commonly used due to their compositional similarity to natural bone. Additional components, such as growth factors, autogenous bone, and therapeutic elements, can be incorporated into synthetic or xenogeneic scaffolds to enhance their osteogenic properties. This review aims to provide a comprehensive analysis of grafting materials in dentistry, discussing their properties, advantages, and disadvantages. It also highlights the challenges of analyzing in vivo and clinical studies to select the most suitable option for specific situations.

Bone defects and fractures present significant clinical challenges, particularly in orthopedic and maxillofacial applications. While minor bone defects may be capable of healing naturally, those of a critical size necessitate intervention through the use of implants or grafts. The utilization of traditional methodologies, encompassing autografts and allografts, is constrained by several factors. These include the potential for donor site morbidity, the restricted availability of suitable donors, and the possibility of immune rejection. This has prompted extensive research in the field of bone tissue engineering to develop advanced synthetic and bio-derived materials that can support bone regeneration. The optimal bone substitute must achieve a balance between biocompatibility, bioresorbability, osteoconductivity, and osteoinductivity while simultaneously providing mechanical support during the healing process. Recent innovations include the utilization of three-dimensional printing, nanotechnology, and bioactive coatings to create scaffolds that mimic the structure of natural bone and enhance cell proliferation and differentiation. Notwithstanding the advancements above, challenges remain in optimizing the controlled release of growth factors and adapting materials to various clinical contexts. This review provides a comprehensive overview of the current advancements in bone substitute materials, focusing on their biological mechanisms, design considerations, and clinical applications. It explores the role of emerging technologies, such as additive manufacturing and stem cell-based therapies, in advancing the field. Future research highlights the need for multidisciplinary collaboration and rigorous testing to develop advanced bone graft substitutes, improving outcomes and quality of life for patients with complex defects.

Bone substitutes are being increasingly used in surgery as over two millions bone grafting procedures are performed worldwide per year. Autografts still represent the gold standard for bone substitution, though the morbidity and the inherent limited availability are the main limitations. Allografts, i.e. banked bone, are osteoconductive and weakly osteoinductive, though there are still concerns about the residual infective risks, costs and donor availability issues. As an alternative, xenograft substitutes are cheap, but their use provided contrasting results, so far. Ceramic-based synthetic bone substitutes are alternatively based on hydroxyapatite (HA) and tricalcium phosphates, and are widely used in the clinical practice. Indeed, despite being completely resorbable and weaker than cortical bone, they have exhaustively proved to be effective. Biomimetic HAs are the evolution of traditional HA and contains ions (carbonates, Si, Sr, Fl, Mg) that mimic natural HA (biomimetic HA). Injectable cements represent another evolution, enabling mininvasive techniques. Bone morphogenetic proteins (namely BMP2 and 7) are the only bone inducing growth factors approved for human use in spine surgery and for the treatment of tibial nonunion. Demineralized bone matrix and platelet rich plasma did not prove to be effective and their use as bone substitutes remains controversial. Experimental cell-based approaches are considered the best suitable emerging strategies in several regenerative medicine application, including bone regeneration. In some cases, cells have been used as bioactive vehicles delivering osteoinductive genes locally to achieve bone regeneration. In particular, mesenchymal stem cells have been widely exploited for this purpose, being multipotent cells capable of efficient osteogenic potential. Here we intend to review and update the alternative available techniques used for bone fusion, along with some hints on the advancements achieved through the experimental research in this field.

Bioactive glasses (BGs) have been a focus of research for over five decades for several biomedical applications. Although their use in bone substitution and bone tissue regeneration has gained important attention, recent developments have also seen the expansion of BG applications to the field of soft tissue engineering. Hard and soft tissue repair therapies can benefit from the biological activity of metallic ions released from BGs. These metallic ions are incorporated in the BG network not only for their biological therapeutic effects but also in many cases for influencing the structure and processability of the glass and to impart extra functional properties. The “classical” elements in silicate BG compositions are silicon (Si), phosphorous (P), calcium (Ca), sodium (Na), and potassium (K). In addition, other well-recognized biologically active ions have been incorporated in BGs to provide osteogenic, angiogenic, anti-inflammatory, and antibacterial effects such as zinc (Zn), magnesium (Mg), silver (Ag), strontium (Sr), gallium (Ga), fluorine (F), iron (Fe), cobalt (Co), boron (B), lithium (Li), titanium (Ti), and copper (Cu). More recently, rare earth and other elements considered less common or, some of them, even “exotic” for biomedical applications, have found room as doping elements in BGs to enhance their biological and physical properties. For example, barium (Ba), bismuth (Bi), chlorine (Cl), chromium (Cr), dysprosium (Dy), europium (Eu), gadolinium (Gd), ytterbium (Yb), thulium (Tm), germanium (Ge), gold (Au), holmium (Ho), iodine (I), lanthanum (La), manganese (Mn), molybdenum (Mo), nickel (Ni), niobium (Nb), nitrogen (N), palladium (Pd), rubidium (Rb), samarium (Sm), selenium (Se), tantalum (Ta), tellurium (Te), terbium (Tb), erbium (Er), tin (Sn), tungsten (W), vanadium (V), yttrium (Y) as well as zirconium (Zr) have been included in BGs. These ions have been found to be particularly interesting for enhancing the biological performance of doped BGs in novel compositions for tissue repair (both hard and soft tissue) and for providing, in some cases, extra functionalities to the BG, for example fluorescence, luminescence, radiation shielding, anti-inflammatory, and antibacterial properties. This review summarizes the influence of incorporating such less-common elements in BGs with focus on tissue engineering applications, usually exploiting the bioactivity of the BG in combination with other functional properties imparted by the presence of the added elements.

Zinc is a micronutrient of key importance for human health. An increasing number of studies indicate that zinc plays a significant role in bone tissue’s normal development and maintaining homeostasis. Zinc is not only a component of bone tissue but is also involved in the synthesis of the collagen matrix, mineralization, and bone turnover. It has been demonstrated that zinc can stimulate runt-related transcription factor 2 (Runx2) and promote the differentiation of osteoblasts. On the other hand, zinc has been found to inhibit osteoclast-like cell formation and to decrease bone resorption by stimulating osteoclasts’ apoptosis. Moreover, zinc regulates the RANKL/RANK/OPG pathway, thereby facilitating bone remodeling. To date, not all mechanisms of Zn activity on bone tissue are well understood and documented. The review aimed to present the current state of research on the role of zinc in bone tissue, its beneficial properties, and its effects on bone regeneration. Since calcium phosphates as bone substitute materials are increasingly enriched in zinc ions, the paper included an overview of research on the potential role of such materials in bone filling and regeneration.

In recent years, the management of bone defects in regenerative medicine and orthopedic surgery has been the subject of extensive research efforts. The complexity of fractures and bone loss arising from trauma, degenerative conditions, or congenital disorders necessitates innovative therapeutic strategies to promote effective healing. Although bone tissue exhibits an intrinsic regenerative capacity, extensive fractures and critical-sized defects can severely compromise this process, often requiring bone grafts or substitutes. Tissue engineering approaches within regenerative medicine have introduced novel possibilities for addressing nonunions and challenging bone defects refractory to conventional treatment methods. Key components in this field include stem cells, bioactive growth factors, and biocompatible scaffolds, with a strong focus on advancements in bone substitute materials. Both natural and synthetic substitutes present distinct characteristics and applications. Natural grafts—comprising autologous, allogeneic, and xenogeneic materials—offer biological advantages, while synthetic alternatives, including biodegradable and non-biodegradable biomaterials, provide structural versatility and reduced immunogenicity. This review provides a comprehensive analysis of the diverse bone grafting alternatives utilized in orthopedic surgery, emphasizing recent advancements and persistent challenges. By exploring both natural and synthetic bone substitutes, this work offers an in-depth examination of cutting-edge solutions, fostering further research and innovation in the treatment of complex bone defects.

Objectives After tooth extraction, the alveolar ridge undergoes significant absorption, and the alveolar ridge preservation (ARP) will alleviate the complexity of implantation operations in specific clinical occasions and then improve the functionality and aesthetics of subsequent restoration. However, the effectiveness of β-tricalcium phosphate (β-TCP) composite materials for ARP needs to be confirmed by more clinical trials and more sufficient evidence. This study was aimed at evaluating the effects of β-TCP coating porous bovine deproteinization bone (β-TCP/PBDB) on ARP when compared with Bio-Oss ® . Materials and methods After baseline clinical examination, teeth extractions and the ARP were conducted randomly by β-TCP/PBDB or the Bio-Oss ® . A collagen sponge was applied over the bone substitutes. After 6 months, clinical examination and cone-beam computerized tomography (CBCT) imaging analysis were conducted to evaluate the changes in alveolar bone volume. Results In the clinical trial, a total of 123 patients successfully completed the protocol. The surgical socket and the soft tissues healed well. The reduction of alveolar ridge width was 1.27 ± 1.32 mm, 0.89 ± 1.31 mm, and 0.63 ± 1.37 mm at three levels (1 mm, 3 mm, 5 mm) below the crest of alveolar ridge respectively using β-TCP/PBDB, while those were 1.12 ± 1.65 mm, 0.55 ± 1.41 mm, 0.56 ± 1.32 mm respectively in the Bio-Oss ® group. The reduction of alveolar ridge height was 0.75 ± 1.96 mm in buccal and 0.95 ± 1.96 mm in lingual using β-TCP/PBDB while those were 1.01 ± 2.44 mm and 0.99 ± 2.13 mm respectively in the Bio-Oss ® group. There is no significant difference in the width and height changes of the alveolar ridge compared to Bio-Oss ® ( p  > 0.05). Conclusions This prospective, randomized, controlled clinical trial provided evidence that β-TCP/PBDB is a safe material and the effectiveness of β-TCP/PBDB in maintaining the volume and contour of the alveolar ridge is comparable to that of the Bio-Oss ® material. Clinical relevance The β-TCP/PBDB can be used as one option of bone substitute material for ARP.

Background Our study aim was to compare allogeneic cancellous bone (ACB) and synthetic or highly-processed xenogeneic bone substitutes (SBS) in the treatment of skeletal defects in orthopedic surgery. Methods 232 patients treated for bony lesions with ACB ( n  = 116) or SBS ( n  = 116) within a 10-year time period were included in this case–control study. Furthermore, both materials were seeded with human osteoblasts (hOB, n  = 10) and analyzed by histology, for viability (AlamarBlue®) and protein expression activity (Luminex®). Results The complication rate was 14.2 %, proportion of defects without bony healing 3.6 %; neither outcome parameter differed comparing the intervention groups. Failed consolidation correlated with an increase in complications ( p  < 0.03). The rate of complications was further highly significant in association with the location of use ( p  < 0.001), but did not depend on age, ASA risk classification, BMI, smoking behavior or type of insurance. However, those factors did significantly influence the bony healing rate ( p  < 0.02). Complication and consolidation rates were independent of gender and the filling substances employed within the different locations. Histological examination revealed similar bone structures, whereas cell remnants were apparent only in the allografts. Both materials were biocompatible in-vitro, and seeded with human osteoblasts. The cells remained vital over the 3-week culture period and produced microscopically typical bone matrix. We observed initially increased expression of osteocalcin, osteopontin, and osteoprotegerin as well as leptin and adiponectin secretion declining after 1 week, especially in the ACB group. Conclusion Although both investigated materials appeared to be similarly suitable for the treatment of skeletal lesions in-vivo and in-vitro, outcome was decisively influenced by other factors such as the site of use or epidemiological parameters.

This systematic review is aimed at evaluating the effectiveness of synthetic block materials for bone augmentation in preclinical in vivo studies. An electronic search was performed on Pubmed, Scopus, EMBASE. Articles selected underwent risk-of-bias assessment. The outcomes were: new bone formation and residual graft with histomorphometry, radiographic bone density, soft tissue parameters, complications. Meta-analysis was performed to compare new bone formation in test (synthetic blocks) vs. control group (autogenous blocks or spontaneous healing). The search yielded 214 articles. After screening, 39 studies were included, all performed on animal models: rabbits (n = 18 studies), dogs (n = 4), rats (n = 7), minipigs (n = 4), goats (n = 4), and sheep (n = 2). The meta-analysis on rabbit studies showed significantly higher new bone formation for synthetic blocks with respect to autogenous blocks both at four-week (mean difference (MD): 5.91%, 95% confidence intervals (CI): 1.04, 10.79%, p = 0.02) and at eight-week healing (MD: 4.44%, 95% CI: 0.71, 8.17%, p = 0.02). Other animal models evidenced a trend for better outcomes with synthetic blocks, though only based on qualitative analysis. Synthetic blocks may represent a viable resource in bone regenerative surgery for achieving new bone formation. Differences in the animal models, the design of included studies, and the bone defects treated should be considered when generalizing the results. Clinical studies are needed to confirm the effectiveness of synthetic blocks in bone augmentation procedures.

In this research, we synthesize and characterize poly(glycerol sebacate) pre-polymer (pPGS) (1H NMR, FTiR, GPC, and TGA). Nano-hydroxyapatite (HAp) is synthesized using the wet precipitation method. Next, the materials are used to prepare a PGS-based composite with a 25 wt.% addition of HAp. Microporous composites are formed by means of thermally induced phase separation (TIPS) followed by thermal cross-linking (TCL) and salt leaching (SL). The manufactured microporous materials (PGS and PGS/HAp) are then subjected to imaging by means of SEM and µCT for the porous structure characterization. DSC, TGA, and water contact angle measurements are used for further evaluation of the materials. To assess the cytocompatibility and biological potential of PGS-based composites, preosteoblasts and differentiated hFOB 1.19 osteoblasts are employed as in vitro models. Apart from the cytocompatibility, the scaffolds supported cell adhesion and were readily populated by the hFOB1.19 preosteoblasts. HAp-facilitated scaffolds displayed osteoconductive properties, supporting the terminal differentiation of osteoblasts as indicated by the production of alkaline phosphatase, osteocalcin and osteopontin. Notably, the PGS/HAp scaffolds induced the production of significant amounts of osteoclastogenic cytokines: IL-1β, IL-6 and TNF-α, which induced scaffold remodeling and promoted the reconstruction of bone tissue. Initial biocompatibility tests showed no signs of adverse effects of PGS-based scaffolds toward adult BALB/c mice.