Search Results (17)

Bone regeneration has emerged as a critical research and clinical advancement field, fueled by the growing demand for effective treatments in orthopedics and oncology. Over the past two decades, significant progress in biomaterials and surgical techniques has led to the development of novel solutions for treating bone defects, surpassing the use of traditional autologous grafts. This review aims to assess the latest approaches in bone regeneration, including autologous, allogenic, and xenogenic grafts, naturally derived biomaterials, and innovative synthetic substitutes such as bioceramics, bioactive glasses, metals, polymers, composite materials, and other specialized applications. A comprehensive literature search was conducted on PubMed, focusing on studies published between 2019 and 2024, including meta-analyses, reviews, and systematic reviews. The review evaluated a range of bone regeneration strategies, examining the clinical outcomes, materials used, surgical techniques, and the effectiveness of various approaches in treating bone defects. The search identified numerous studies, with the inclusion criteria focused on those exploring innovative bone regeneration strategies. These studies provided valuable insights into the clinical and biological outcomes of different biomaterials and graft types. Results indicated that while advancements in synthetic and naturally derived biomaterials show promising potential, challenges remain in optimizing therapeutic strategies across diverse patient populations and clinical settings. The findings emphasize the need for an integrated approach that combines scientific research, clinical practice, and technological innovation to improve bone regeneration therapies. Further research is required to establish standardized protocols and determine the optimal application of various materials and techniques to enhance patient outcomes and the quality of care. Full article

Autogenous grafts remain the “gold standard” in bone tissue grafting procedures; however, limitations such as donor site morbidity, invasiveness, and limited availability have spurred research into alternative materials. Hydroxyapatite (HA), a widely used bioceramic, is known for its bioactivity and biocompatibility. Nonetheless, its inherent brittleness and porosity necessitate modifications to enhance its mechanical and functional properties. Ionic doping has emerged as a transformative strategy to improve the properties of HA by integrating ions such as strontium (Sr²⁺), magnesium (Mg²⁺), and zinc (Zn²⁺). These dopants influence HA’s crystal structure, morphology, and solubility, resulting in enhanced bioactivity, accelerated bone mineralization, and improved mechanical properties, such as increased fracture resistance and wear durability. Additionally, antimicrobial properties can be achieved through the inclusion of silver ions (Ag⁺), reducing the risk of peri-implant infections. This review focuses on the effects of ionic doping on the structure and functionality of hydroxyapatite, emphasizing advancements in tailoring its properties to clinical needs. By consolidating two decades of research, this study highlights how ionic doping bridges the gap between synthetic biomaterials and native bone, unlocking new potential in regenerative medicine and orthopedic applications. Full article

Large osseous defects resulting from trauma, tumor resection, or fracture render the inherent ability of the body to repair inadequate and necessitate the use of bone grafts to facilitate the recovery of both form and function of the bony defect sites. In the United States alone, a large number of bone graft procedures are performed yearly, making it an essential area of investigation and research. Synthetic grafts represent a potential alterative to autografts due to their patient-specific customizability, but currently lack widespread acceptance in the clinical space. Early in their development, non-autologous bone grafts composed of metals such as stainless steel and titanium alloys were favorable due to their biocompatibility, resistance to corrosion, mechanical strength, and durability. However, since their inception, bioceramics have also evolved as viable alternatives. This review aims to present an overview of the fundamental prerequisites for tissue engineering devices using bioceramics as well as to provide a comprehensive account of their historical usage and significant advancements over time. This review includes a summary of commonly used manufacturing techniques and an evaluation of their use as drug carriers and bioactive coatings—for therapeutic ion/drug release, and potential avenues to further enhance hard tissue regeneration. Full article

(1) Background: The desire to avoid autograft harvesting in implant dentistry has prompted an ever-increasing quest for bioceramic bone substitutes, which stimulate osteogenesis while resorbing in a timely fashion. Consequently, a highly bioactive silicon containing calcium alkali orthophosphate (Si-CAP) material was created, which previously was shown to induce greater bone cell maturation and bone neo-formation than β-tricalcium phosphate (β-TCP) in vivo as well as in vitro. Our study tested the hypothesis that the enhanced effect on bone cell function in vitro and in sheep in vivo would lead to more copious bone neoformation in patients following sinus floor augmentation (SFA) employing Si-CAP when compared to β-TCP. (2) Methods: The effects of Si-CAP on osteogenesis and Si-CAP resorbability were evaluated in biopsies harvested from 38 patients six months after SFA in comparison to β-TCP employing undecalcified histology, histomorphometry, and immunohistochemical analysis of osteogenic marker expression. (3) Results: Si-CAP as well as β-TCP supported matrix mineralization and bone formation. Apically furthest away from the original bone tissue, Si-CAP induced significantly higher bone formation, bone-bonding (bone-bioceramic contact), and granule resorption than β-TCP. This was in conjunction with a higher expression of osteogenic markers. (4) Conclusions: Si-CAP induced higher and more advanced bone formation and resorbability than β-TCP, while β-TCP’s remarkable osteoconductivity has been widely demonstrated. Hence, Si-CAP constitutes a well-suited bioactive graft choice for SFA in the clinical arena. Full article

Critical bone defects are the most difficult challenges in the area of tissue repair. Polycaprolactone (PCL) scaffolds, associated with hydroxyapatite (HA) and tricalcium phosphate (TCP), are reported to have an enhanced bioactivity. Moreover, the use of electrical stimulation (ES) has overcome the lack of bioelectricity at the bone defect site and compensated the endogenous electrical signals. Such treatments could modulate cells and tissue signaling pathways. However, there is no study investigating the effects of ES and bioceramic composite scaffolds on bone tissue formation, particularly in the view of cell signaling pathway. This study aims to investigate the application of HA/TCP composite scaffolds and ES and their effects on the Wingless-related integration site (Wnt) pathway in critical bone repair. Critical bone defects (25 mm²) were performed in rats, which were divided into four groups: PCL, PCL + ES, HA/TCP and HA/TCP + ES. The scaffolds were grafted at the defect site and applied with the ES application twice a week using 10 µA of current for 5 min. Bone samples were collected for histomorphometry, immunohistochemistry and molecular analysis. At the Wnt canonical pathway, HA/TCP and HA/TCP + ES groups showed higher Wnt1 and β-catenin gene expression levels, especially HA/TCP. Moreover, HA/TCP + ES presented higher Runx2, Osterix and Bmp-2 levels. At the Wnt non-canonical pathway, HA/TCP group showed higher voltage-gated calcium channel (Vgcc), calmodulin-dependent protein kinase II, and Wnt5a genes expression, while HA/TCP + ES presented higher protein expression of VGCC and calmodulin (CaM) at the same period. The decrease in sclerostin and osteopontin genes expressions and the lower bone sialoprotein II in the HA/TCP + ES group may be related to the early bone remodeling. This study shows that the use of ES modulated the Wnt pathways and accelerated the osteogenesis with improved tissue maturation. Full article

Various types of materials have been traditionally used to restore damaged bones. In the late 1960s, a strong interest was raised in studying ceramics as potential bone grafts due to their biomechanical properties. A short time later, such synthetic biomaterials were called bioceramics. Bioceramics can be prepared from diverse inorganic substances, but this review is limited to calcium orthophosphate (CaPO₄)-based formulations only, due to its chemical similarity to mammalian bones and teeth. During the past 50 years, there have been a number of important achievements in this field. Namely, after the initial development of bioceramics that was just tolerated in the physiological environment, an emphasis was shifted towards the formulations able to form direct chemical bonds with the adjacent bones. Afterwards, by the structural and compositional controls, it became possible to choose whether the CaPO₄-based implants would remain biologically stable once incorporated into the skeletal structure or whether they would be resorbed over time. At the turn of the millennium, a new concept of regenerative bioceramics was developed, and such formulations became an integrated part of the tissue engineering approach. Now, CaPO₄-based scaffolds are designed to induce bone formation and vascularization. These scaffolds are usually porous and harbor various biomolecules and/or cells. Therefore, current biomedical applications of CaPO₄-based bioceramics include artificial bone grafts, bone augmentations, maxillofacial reconstruction, spinal fusion, and periodontal disease repairs, as well as bone fillers after tumor surgery. Prospective future applications comprise drug delivery and tissue engineering purposes because CaPO₄ appear to be promising carriers of growth factors, bioactive peptides, and various types of cells. Full article

The addition of Mn in bioceramic formulation is gaining interest in the field of bone implants. Mn activates human osteoblast (h-osteoblast) integrins, enhancing cell proliferation with a dose-dependent effect, whereas Mn-enriched glasses induce inhibition of Gram-negative or Gram-positive bacteria and fungi. In an effort to further optimize Mn-containing scaffolds’ beneficial interaction with h-osteoblasts, a selective and specific covalent functionalization with a bioactive peptide was carried out. The anchoring of a peptide, mapped on the BMP-2 wrist epitope, to the scaffold was performed by a reaction between an aldehyde group of the peptide and the aminic groups of silanized Mn-containing bioceramic. SEM-EDX, FT-IR, and Raman studies confirmed the presence of the peptide grafted onto the scaffold. In in vitro assays, a significant improvement in h-osteoblast proliferation, gene expression, and calcium salt deposition after 7 days was detected in the functionalized Mn-containing bioceramic compared to the controls. Full article

The usual treatment for bone defects and recalcitrant nonunions is an autogenous bone graft. However, due to the limitations in obtaining autogenous bone grafts and the morbidity associated with their procurement, various bone healing materials have been developed in recent years. The three main treatment strategies for bone defects and recalcitrant nonunions are synthetic bone graft substitutes (BGS), BGS combined with bioactive molecules, and BGS and stem cells (cell-based constructs). Regarding BGS, numerous biomaterials have been developed to prepare bone tissue engineering scaffolds, including biometals (titanium, iron, magnesium, zinc), bioceramics (hydroxyapatite (HA)), tricalcium phosphate (TCP), biopolymers (collagen, polylactic acid (PLA), polycaprolactone (PCL)), and biocomposites (HA/MONs@miR-34a composite coating, Bioglass (BG)-based ABVF-BG (antibiotic-releasing bone void filling) putty). Bone tissue engineering scaffolds are temporary implants that promote tissue ingrowth and new bone regeneration. They have been developed to improve bone healing through appropriate designs in terms of geometric, mechanical, and biological performance. Concerning BGS combined with bioactive molecules, one of the most potent osteoinductive growth factors is bone morphogenetic proteins (BMPs). In recent years, several natural (collagen, fibrin, chitosan, hyaluronic acid, gelatin, and alginate) and synthetic polymers (polylactic acid, polyglycolic acid, polylactic-coglycolide, poly(e-caprolactone) (PCL), poly-p-dioxanone, and copolymers consisting of glycolide/trimethylene carbonate) have been investigated as potential support materials for bone tissue engineering. Regarding BGS and stem cells (cell-based constructs), the main strategies are bone marrow stromal cells, adipose-derived mesenchymal cells, periosteum-derived stem cells, and 3D bioprinting of hydrogels and cells or bioactive molecules. Currently, significant research is being performed on the biological treatment of recalcitrant nonunions and bone defects, although its use is still far from being generalized. Further research is needed to investigate the efficacy of biological treatments to solve recalcitrant nonunions and bone defects. Full article

This review summarizes the results reported on the production of biphasic calcium phosphate (BCP) materials derived from fish wastes (i.e., heads, bones, skins, and viscera), known as fish discards, and offers an in-depth discussion on their promising potential for various applications in many fields, especially the biomedical one. Thus, considerable scientific and technological efforts were recently focused on the capability of these sustainable materials to be transformed into economically attractive and highly valuable by-products. As a consequence of using these wastes, plenty of beneficial social effects, with both economic and environmental impact, will arise. In the biomedical field, there is a strong and continuous interest for the development of innovative solutions for healthcare improvement using alternative materials of biogenic origin. Thus, the orthopedic field has witnessed a significant development due to an increased demand for a large variety of implants, grafts, and/or scaffolds. This is mainly due to the increase of life expectancy and higher frequency of bone-associated injuries and diseases. As a consequence, the domain of bone-tissue engineering has expanded to be able to address a plethora of bone-related traumas and to deliver a viable and efficient substitute to allografts or autografts by combining bioactive materials and cells for bone-tissue ingrowth. Among biomaterials, calcium phosphate (CaP)-based bio-ceramics are widely used in medicine, in particular in orthopedics and dentistry, due to their excellent bioactive, osteoconductive, and osteointegrative characteristics. Recently, BCP materials (synthetic or natural), a class of CaP, which consist of a mixture of two phases, hydroxyapatite (HA) and beta tricalcium phosphate (β-TCP), in different concentrations, gained increased attention due to their superior overall performances as compared to single-phase formulations. Moreover, the exploitation of BCP materials from by-products of fish industry was reported to be a safe, cheap, and simple procedure. In the dedicated literature, there are many reviews on synthetic HA, β-TCP, or BCP materials, but to the best of our knowledge, this is the first collection of results on the effects of processing conditions on the morphological, compositional, structural, mechanical, and biological properties of the fish discard-derived BCPs along with the tailoring of their features for various applications. Full article

Natural bone tissue consists primarily of bioapatite and collagen. Synthetic hydroxyapatite (HA) possesses good biocompatibility, bioactivity, and osteoconductivity due to its chemical and biological similarity to bioapatite. Hence, HA has been widely used as a bone graft, cell carrier and drug/gene delivery carrier. Moreover, strontium-substituted hydroxyapatite (SrHA) can enhance osteogenic differentiation and inhibit adipogenic differentiation of mesenchymal stem cells. Hence, SrHA has the potential to be used as a bone graft for bone regeneration. It is widely accepted that cell adhesion and most cellular activities are sensitive to the topography and molecular composition of the matrix. Electrospun polymer or polymer-bioceramic composite nanofibers have been demonstrated to enhance osteoblast differentiation. However, to date, no studies have investigated the effect of nanofibrous bioceramic matrices on osteoblasts. In this study, hydroxyapatite nanofiber (HANF) and strontium-substituted hydroxyapatite nanofiber (SrHANF) matrices were fabricated by electrospinning. The effect of the HANF components on MG63 osteoblast-like cells was evaluated by cell morphology, proliferation, alkaline phosphatase activity (ALP) and gene expression levels of RUNX2, COLI, OCN and BSP. The results showed that MG63 osteoblast-like cells exhibited higher ALP and gene expression levels of RUNX2, COLI, BSP and OCN on the SrHANF matrix than the HANF matrix. Hence, SrHANFs could enhance the differentiation of MG63 osteoblast-like cells. Full article

With the increased incidence of bone defects following trauma or diseases in recent years, three-dimensional porous scaffolds fabricated using bioprinting technologies have been widely explored as effective alternatives to conventional bone grafts, which provide cell-friendly microenvironments promoting bone repair and regeneration. However, the limited use of biomaterials poses a significant challenge to the robust and accurate fabrication of bioprinted bone scaffolds that enable effective regeneration of the target tissues. Although bioceramic/polymer composites can provide tunable biomimetic conditions, their effects on the bioprinting process are unclear. Thus, in this study, we fabricated hydroxyapatite (HA)/gelatin composite scaffolds containing large weight fractions of HA using extrusion-based bioprinting, with the aim to provide an adequate biomimetic environment for bone tissue regeneration with compositional and mechanical similarity to the natural bone matrix. The overall features of the bioprinted HA/gelatin composite scaffolds, including rheological, morphological, physicochemical, mechanical, and biological properties, were quantitatively assessed to determine the optimal conditions for both fabrication and therapeutic efficiency. The present results show that the bioprinted bioceramic/hydrogel scaffolds possess excellent shape fidelity; mechanical strength comparable to that of native bone; and enhanced bioactivity in terms of cell proliferation, attachment, and osteogenic differentiation. This study provides a suitable alternative direction for the fabrication of bioceramic/hydrogel-based scaffolds for bone repair based on bioprinting. Full article

The healing of oral lesions that are associated with diabetes mellitus is a matter of great concern. Bioactive glass is a highly recommended bioceramic scaffold for bone and soft tissue regeneration. In this study, we aimed to assess the efficacy of a novel formula of bioactive glass nanofibers in enhancing oral mucosal wound regeneration in diabetes mellitus. Bioactive glass nanofibres (BGnf) of composition (1–2) mol% of B₂O₃, (68–69) mol% of SiO₂, and (29–30) mol% of CaO were synthesized via the low-temperature sol-gel technique followed by mixing with polymer solution, then electrospinning of the glass sol to produce nanofibers, which were then subjected to heat treatment. X-Ray Diffraction analysis of the prepared nanofibers confirmed its amorphous nature. Microstructure of BGnf simulated that of the fibrin clot with cross-linked nanofibers having a varying range of diameter (500–900 nm). The in-vitro degradation profile of BGnf confirmed its high dissolution rate, which proved the glass bioactivity. Following fibers preparation and characterization, 12 healthy New Zealand male rabbits were successfully subjected to type I diabetic induction using a single dose of intravenous injection of alloxan monohydrate. Two weeks after diabetes confirmation, the rabbits were randomly divided into two groups (control and experimental groups). Bilateral elliptical oral mucosal defects of 10 × 3.5 mm were created in the maxillary mucobuccal fold of both groups. The defects of the experimental group were grafted with BGnf, while the other group of defects considered as a control group. Clinical, histological, and immune-histochemical assessment of both groups of wounds were performed after one, two and three weeks’ time interval. The results of the clinical evaluation of BGnf treated defects showed complete wound closure with the absence of inflammation signs starting from one week postoperative. Control defects, on the other hand, showed an open wound with suppurative exudate. On histological and immunohistochemical level, the BGnf treated defects revealed increasing in cell activity and vascularization with the absence of inflammation signs starting from one week time interval, while the control defects showed signs of suppurative inflammation at one week time interval with diminished vascularization. The results advocated the suitability of BGnf as bioscaffold to be used in a wet environment as the oral cavity that is full of microorganisms and also for an immune-compromised condition as diabetes mellitus. Full article

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. Full article

Periodontal diseases involve injuries to the supporting structures of the tooth and, if left untreated, can lead to the loss of the tooth. Regenerative periodontal therapies aim, ideally, at healing all the damaged periodontal tissues and represent a significant clinical and societal challenge for the current ageing population. This review provides a picture of the currently-used biomaterials for periodontal regeneration, including natural and synthetic polymers, bioceramics (e.g., calcium phosphates and bioactive glasses), and composites. Bioactive materials aim at promoting the regeneration of new healthy tissue. Polymers are often used as barrier materials in guided tissue regeneration strategies and are suitable both to exclude epithelial down-growth and to allow periodontal ligament and alveolar bone cells to repopulate the defect. The problems related to the barrier postoperative collapse can be solved by using a combination of polymeric membranes and grafting materials. Advantages and drawbacks associated with the incorporation of growth factors and nanomaterials in periodontal scaffolds are also discussed, along with the development of multifunctional and multilayer implants. Tissue-engineering strategies based on functionally-graded scaffolds are expected to play an ever-increasing role in the management of periodontal defects. Full article

It is important for oral and maxillofacial surgeons to repair craniofacial defects on oral cancer patients or patients with congenital problems. Thus, it is a challenge to develop biomaterials that promote bone regeneration as potential materials for bone repair. This work is devoted to the fabrication of bioceramics composed of silica and titanium oxide with various concentrations of titanium oxide for developing bone repair materials for dentistry and tissue engineering. The silica-based bioceramics were synthesized using the sol–gel method, and titanium oxide was added from the hydrolysis of tetrabutyl titanate. The surface morphology was observed using scanning electron microscopy. The chemical composition was measured using an energy dispersive X-ray spectrometer, and the crystal structure was identified by using an X-ray diffraction diffractometer. The pH value and ion concentrations released in simulated body fluids after immersion with bioceramic samples were measured using a pH meter and inductively coupled plasma mass spectrometry, respectively. In the cell toxicity test, the human osteosarcoma cells (MG63) were used and quantitatively assessed using an MTT assay. The results showed that the proposed bioceramics can be controlled by tuning the Si/Ti ratio to modify the dissolution rate of samples and enhance the formation of apatite. Compared to Dulbecco’s modified Eagle’s medium (DMEM) groups, the cell number of the BG_Ti75 group can be increased to 120%. Furthermore, BG_Ti75 can promote MG63 cell growth with statistical significance and keep the pH value and the released calcium ion concentrations of the soaking environment stable. The proposed bioceramics show potential for bone-regenerating capability. Full article