With the exception of blood, bone and cartilage grafts are the most common form of transplanted tissue in the world. Many graft materials are available to utilise in head and neck reconstruction with an array of oncologic, traumatic, congenital and cosmetic applications. Accordingly, it is imperative to understand the complications associated with these grafts, especially in relation to specific materials available.

Infection, warping, resorption and donor site morbidity are the most commonly reported complications in the literature. In relation to cartilage grafts, autologous costal cartilage is the preferred material owing to low immunogenicity and ease of harvest. However, with the disadvantage of donor site morbidity, more recent literature has shown comparable complication rates with allogenic fresh frozen and irradiated costal cartilage. Alloplastic grafts have been associated with concern for a higher risk of complications, although there is a lack of high-quality studies to demonstrate this risk. Bone is subject to similar complications with the exception of graft warping. However, bone grafts are typically used to treat more significant and sizeable defects, which can engender more severe complications.

Complications regarding grafting of cartilaginous and bony material to the head and neck continue to evolve in the literature. Advances in graft material, including the advent of bio-engineered tissue, remain a developing area with auspicious prospects.

The development of biomaterials that enhance bone healing and integrate with native bone tissue has gained significant interest. Metal-organic frameworks (MOFs) have emerged as promising candidates due to their unique surface properties and biocompatibility. While various bioactive element-incorporated MOFs have been studied, the osteogenic potential of lithium (Li)-modified MOFs remains largely unexplored. This study presents the synthesis and characterization of a nanosized calcium-based MOF incorporating Li⁺ ions to enhance osteoinductive properties. The MOFs were evaluated in vitro for apatite mineralization, degradation, ion release, protein adsorption, cell adhesion, viability, and osteogenic differentiation using pre-osteoblast cells. The synthesized MOFs promoted apatite formation under simulated physiological conditions, facilitated by their surface nucleation properties, controlled degradation, and sustained Li+ and Ca2+ ion release. Cytocompatibility assays confirmed excellent pre-osteoblast adhesion and viability. Furthermore, CaMOF nanoparticles stimulated osteogenic differentiation by enhancing alkaline phosphatase (ALP) activity, even in the absence of osteogenic supplements. Among tested MOFs, Li/CaMOF exhibited the highest osteoinductive potential. These findings highlight lithium-modified MOFs as promising biomaterials for bone regeneration. However, further in vivo studies are necessary to assess their long-term stability, bone integration, and clinical applicability.

Current treatments for congenital and acquired craniofacial (CF) bone abnormalities are limited and costly. Conventional methods involve surgical correction, short-term stabilization, and long-term bone grafting, which may include problematic allografts and limited autografts. While bone morphogenetic protein 2 (BMP2) has been used for bone regeneration, it can cause bone overgrowth and life-threatening inflammation. Bone marrow-derived mesenchymal stem cell therapies, though promising, are not Food and Drug Administration approved and are resource intensive. Thus, there is a need for effective, affordable, and less side-effect-prone bone regenerative therapies. Previous research demonstrated that JAGGED1 induces osteoblast commitment in murine cranial neural crest cells through a NOTCH-dependent non-canonical pathway involving JAK2-STAT5. We hypothesize that delivery of JAGGED1 and induction of its downstream NOTCH non-canonical signaling in pediatric human osteoblasts constitutes an effective bone regenerative treatment. Delivering pediatric human bone-derived osteoblast-like cells to an in vivo murine bone loss model of a critically sized cranial defect, we identified that JAGGED1 promotes human pediatric osteoblast commitment and bone formation through p70 S6K phosphorylation. This approach highlights the potential of JAGGED1 and its downstream activators as innovative treatments for pediatric CF bone loss.

Alveolar bone loss in elderly populations is highly prevalent and increases the risk of tooth loss, gum disease susceptibility, and facial deformity. Unfortunately, there are very limited treatment options available. Here, we developed a bone-targeted gene therapy that reverses alveolar bone loss in patients with osteoporosis by targeting the adaptor protein Schnurri-3 (SHN3). SHN3 is a promising therapeutic target for alveolar bone regeneration, because SHN3 expression is elevated in the mandible tissues of humans and mice with osteoporosis while deletion of SHN3 in mice greatly increases alveolar bone and tooth dentin mass. We used a bone-targeted recombinant adeno-associated virus (rAAV) carrying an artificial microRNA (miRNA) that silences SHN3 expression to restore alveolar bone loss in mouse models of both postmenopausal and senile osteoporosis by enhancing WNT signaling and osteoblast function. In addition, rAAV-mediated silencing of SHN3 enhanced bone formation and collagen production of human skeletal organoids in xenograft mice. Finally, rAAV expression in the mandible was tightly controlled via liver- and heart-specific miRNA-mediated repression or via a vibration-inducible mechanism. Collectively, our results demonstrate that AAV-based bone anabolic gene therapy is a promising strategy to treat alveolar bone loss in osteoporosis.

Clinical concerns exist regarding the quality of bony consolidation in the context of the induced membrane technique. This study evaluates the clinical process of bone grafting in the second stage of induced membrane bone union in patients with tibial bone defects to infer the possibility of non-union and establish a reliable and effective evaluation method combined with computed tomography (CT) to assess fracture healing.

Patients with tibial bone defects who underwent the induced membrane technique at our hospital between February 2017 and February 2020 were retrospectively analyzed. The Hounsfield unit (HU) values of the patients were evaluated at different times during the second stage of bone grafting. Bone healing at the boundary value of the 120 HU output threshold (-1024 HU-3071 HU) was directionally selected, and the changes in the growth volume of union (new bone volume [selected according to HU value]/bone defect volume) were compared with analyzing individual class bone union. Method 1 involved X-rays revealing that at least three of the four cortices were continuous and at least 2 mm thick, with the patient being pain free. For Method 2, new bone volume (selected according to HU value/bone defect volume) at the stage was compared with analyzing individual class healing. Receiver operating characteristic curve analysis was used for Methods 1 and 2.

A total of 42 patients with a segmental bone defect with a mean age of 40.5 years (40.5 ± 8.3 years) were included. The relationship between bone graft volume and time variation was analyzed by single factor repeated variable analysis (F = 6.477, p = 0.016). Further, curve regression analysis showed that the change in bone graft volume over time presented a logarithmic curve pattern (Y = 0.563 + 0.086 × ln(X), Ra2 = 0.608, p = 0.041). ROC curve analysis showed that Method 2 is superior to Method 1 (AUC: 86.3% vs. 68.3%, p < 0.05).

The induced membrane technique could be used to treat traumatic long bone defects, with fewer complications and a higher healing rate. The proposed imaging grading of HU (new bone volume/bone defect volume) can be used as a reference for the quality of bony consolidation with the induced membrane technique.

Bone flap resorption is an issue after autologous cranioplasty. Critical temperatures above 50°C generated by power-driven craniotomy tools may lead to thermal osteonecrosis, a possible factor in resorption. This ex vivo study examined whether the tools produced excessive heat resulting in bone flap resorption.

Using swine scapulae maintained at body temperature, burr holes, straight and curved cuts, and wire-pass holes were made with power-driven craniotomy tools. Drilling was at the conventional feed rate (FR) plus irrigation (FR-I+), at a high FR plus irrigation (hFR-I+), and at high FR without irrigation (hFR-I-). The temperature in each trial was recorded by an infrared thermographic camera.

With FR-I+, the maximum temperature at the burr holes, the cuts, and the wire-pass holes was 69.0°C, 56.7°C, and 46.2°C, respectively. With hFR-I+, these temperatures were 53.1°C, 52.1°C, and 46.0°C, with hFR-I- they were 56.0°C, 66.5°C, and 50.0°C; hFR-I- burr hole- and cutting procedures resulted in the highest incidence of bone temperatures above 50°C followed by FR-I+, and hFR-I+. At the site of wire-pass holes, only hFR-I- drilling produced this temperature.

Except during prolonged procedures in thick bones, most drilling with irrigation did not reach the critical temperature. Drilling without irrigation risked generating the critical temperature. Knowing those characteristics may be a help to perform craniotomy with less thermal bone damage.

Treatments for congenital and acquired craniofacial (CF) bone abnormalities are limited and expensive. Current reconstructive methods include surgical correction of injuries, short-term bone stabilization, and long-term use of bone grafting solutions, including implantation of (i) allografts which are prone to implant failure or infection, (ii) autografts which are limited in supply. Current bone regenerative approaches have consistently relied on BMP2 application with or without addition of stem cells. BMP2 treatment can lead to severe bony overgrowth or uncontrolled inflammation, which can accelerate further bone loss. Bone marrow-derived mesenchymal stem cell-based treatments, which do not have the side effects of BMP2, are not currently FDA approved, and are time and resource intensive. There is a critical need for novel bone regenerative therapies to treat CF bone loss that have minimal side effects, are easily available, and are affordable. In this study we investigated novel bone regenerative therapies downstream of JAGGED1 (JAG1). We previously demonstrated that JAG1 induces murine cranial neural crest (CNC) cells towards osteoblast commitment via a NOTCH non-canonical pathway involving JAK2-STAT5 (1) and that JAG1 delivery with CNC cells elicits bone regeneration in vivo. In this study, we hypothesize that delivery of JAG1 and induction of its downstream NOTCH non-canonical signaling in pediatric human osteoblasts constitute an effective bone regenerative treatment in an in vivo murine bone loss model of a critically-sized cranial defect. Using this CF defect model in vivo, we delivered JAG1 with pediatric human bone-derived osteoblast-like (HBO) cells to demonstrate the osteo-inductive properties of JAG1 in human cells and in vitro we utilized the HBO cells to identify the downstream non-canonical JAG1 signaling intermediates as effective bone regenerative treatments. In vitro, we identified an important mechanism by which JAG1 induces pediatric osteoblast commitment and bone formation involving the phosphorylation of p70 S6K. This discovery enables potential new treatment avenues involving the delivery of tethered JAG1 and the downstream activators of p70 S6K as powerful bone regenerative therapies in pediatric CF bone loss.

Segmental mandibular defects can occur due to various etiologies, including trauma and tumor resection. Reconstruction should provide adequate support for subsequent dental rehabilitation and allow for proper occlusion. Nonvascularized bone grafts have been used for reconstructing mandibular defects in cases where vascularized grafts were not feasible. The objective of this study was to assess the success rate of these grafts in reconstruction of segmental defects of various sizes in the mandible.

Fifty patients were included in this retrospective chart review. Length of the grafts varied from 3 to 20 cm and patients were followed up from 4 to 80 months. Fifteen grafts were harvested from anterior iliac crest, 23 from posterior iliac crest, 9 grafts were a combination of either with costochondral graft, and 3 were solely allografts. Bone morphogenetic protein was utilized in 41 cases as an adjunct.

Success was defined as continuity of bone clinically and radiographically at a 4-month follow-up. Nonvascularized bone grafting was successful in 90% of cases. Complications were observed in 34% of cases, of which the most common were infection followed by wound dehiscence.

Our study demonstrated substantial success rate with nonvascularized bone grafts in reconstruction of segmental mandibular defects.

Periodontitis is a dysbiosis-driven inflammatory disease affecting the tooth-supporting tissues, characterized by their progressive resorption, which can ultimately lead to tooth loss. A step-wise therapeutic approach is employed for periodontitis. After an initial behavioral and non-surgical phase, intra-bony or furcation defects may be amenable to regenerative procedures. This review discusses the regenerative technologies employed for periodontal regeneration, highlighting the current limitations and future research areas. The search, performed on the MEDLINE database, has identified the available biomaterials, including biologicals (autologous platelet concentrates, hydrogels), bone grafts (pure or putty), and membranes. Biologicals and bone grafts have been critically analyzed in terms of composition, mechanism of action, and clinical applications. Although a certain degree of periodontal regeneration is predictable in intra-bony and class II furcation defects, complete defect closure is hardly achieved. Moreover, treating class III furcation defects remains challenging. The key properties required for functional regeneration are discussed, and none of the commercially available biomaterials possess all the ideal characteristics. Therefore, research is needed to promote the advancement of more effective and targeted regenerative therapies for periodontitis. Lastly, improving the design and reporting of clinical studies is suggested by strictly adhering to the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement.

Reconstructing extensive cranial defects represents a persistent clinical challenge. Here, we reported a hybrid three-dimensional (3D) printed scaffold with modification of QK peptide and KP peptide for effectively promoting endogenous cranial bone regeneration. The hybrid 3D printed scaffold consists of vertically aligned cryogel fibers that guide and promote cell penetration into the defect area in the early stages of bone repair. Then, the conjugated QK peptide and KP peptide further regulate the function of the recruited cells to promote vascularization and osteogenic differentiation in the defect area. The regenerated bone volume and surface coverage of the dual peptide-modified hybrid scaffold were significantly higher than the positive control group. In addition, the dual peptide-modified hybrid scaffold demonstrated sustained enhancement of bone regeneration and avoidance of bone resorption compared to the collagen sponge group. We expect that the design of dual peptide-modified hybrid scaffold will provide a promising strategy for bone regeneration.

Infectious bone defects are characterized by the partial loss or destruction of bone tissue resulting from bacterial contaminations subsequent to diseases or external injuries. Traditional bone transplantation and clinical methods are insufficient in meeting the treatment demands for such diseases. As a result, researchers have increasingly focused on the development of more sophisticated biomaterials for improved therapeutic outcomes in recent years. This review endeavors to investigate specific reparative materials utilized for the treatment of infectious bone defects, particularly those present in the maxillofacial region, with a focus on biomaterials capable of releasing therapeutic substances, functional contact biomaterials, and novel physical therapy materials. These biomaterials operate via heightened antibacterial or osteogenic properties in order to eliminate bacteria and/or stimulate bone cells regeneration in the defect, ultimately fostering the reconstitution of maxillofacial bone tissue. Based upon some successful applications of new concept materials in bone repair of other parts, we also explore their future prospects and potential uses in maxillofacial bone repair later in this review. We highlight that the exploration of advanced biomaterials holds promise in establishing a solid foundation for the development of more biocompatible, effective, and personalized treatments for reconstructing infectious maxillofacial defects.

Recent years have witnessed the rapid development of 3D porous scaffolds with excellent biocompatibility, tunable porosity, and pore interconnectivity, sufficient mechanical strength, controlled biodegradability, and favorable osteogenesis for improved results in cranioplasty. However, clinical translation of these scaffolds has lagged far behind, mainly because of the absence of a series of biological evaluations. Herein, we designed and fabricated a composite 3D porous scaffold composed of poly (lactic-co-glycolic) acid (PLGA), β-tricalcium phosphate (β-TCP), and Mg using the low-temperature deposition manufacturing (LDM) technique. The LDM-engineered scaffolds possessed highly porous and interconnected microstructures with a porosity of 63%. Meanwhile, the scaffolds exhibited mechanical properties close to that of cancellous bone, as confirmed by the compression tests. It was also found that the original composition of scaffolds could be maintained throughout the fabrication process. Particularly, two important biologic evaluations designed for non-active medical devices, i.e., local effects after implantation and subchronic systemic toxicity tests, were conducted to evaluate the local and systemic toxicity of the scaffolds. Additionally, the scaffolds exhibited significant higher mRNA levels of osteogenic genes compared to control scaffolds, as confirmed by an in vitro osteogenic differentiation test of MC3T3-E1 cells. Finally, we demonstrated the improved cranial bone regeneration performance of the scaffolds in a rabbit model. We envision that our investigation could pave the way for translating the LDM-engineered composite scaffolds into clinical products for cranial bone regeneration.

Repairing critical-size bone defects still represents a critical clinical challenge in the field of trauma surgery. This study focuses on a physiological design and manufacturing of porous composite scaffold (titanium Ti with 10 % mole iron doped brushite DCPD-Fe3+) which can mimic the biomechanical properties of natural cortical bone, specifically for the purpose of repairing critical-size defects. To achieve this, the principle of design of experiments (DOE) was applied for investigating the impact of sintering temperature, mineral ratio, and volume fraction of porosity on the mechanical properties of the fabricated scaffolds. The fabricated scaffolds had open porosity up to 60 %, with pore size approximately between 100 μm and 850 μm. The stiffness of the porous composite scaffolds varied between 3.30 GPa and 20.50 GPa, while the compressive strength ranged from approximately 130 MPa-165 MPa at sintering temperatures equal to or exceeding 1000 °C. Scaffolds with higher porosity and mineral content demonstrated lower stiffness values, resembling natural bone. Numerical simulation was employed by Ansys Workbench to investigate the stress and strain distribution of a critical size defect in mid-shaft femur which was designed to be replaced with the fabricated scaffold. The fabricated scaffolds showed flexible biomechanical behaviour at the bone/scaffold interface, generating lower stress levels and indicating a better match with the femoral shaft stiffness. The experimental and numerical findings demonstrated promising applications for manufacturing a patient-specific bone scaffold for critical and potentially large defects for reducing stress shielding and minimizing non-union risk.

Reconstruction of critical-size bone defects (CSDs) in the craniomaxillofacial (CMF) region remains challenging. Scaffold-based bone-engineered constructs have been proposed as an alternative to the classical treatments made with autografts and allografts. Scaffolds, a key component of engineered constructs, have been traditionally viewed as biologically passive temporary replacements of deficient bone lacking intrinsic cues to promote osteogenesis. Nowadays, scaffolds are functionalized, giving rise to bioactive scaffolds promoting bone regeneration more effectively than conventional counterparts. This review focuses on the three approaches most used to bioactivate scaffolds: (1) conferring microarchitectural designs or surface nanotopography; (2) loading bioactive molecules; and (3) seeding stem cells on scaffolds, providing relevant examples of in vivo (preclinical and clinical) studies where these methods are employed to enhance CSDs healing in the CMF region. From these, adding bioactive molecules (specifically bone morphogenetic proteins or BMPs) to scaffolds has been the most explored to bioactivate scaffolds. Nevertheless, the downsides of grafting BMP-loaded scaffolds in patients have limited its successful translation into clinics. Despite these drawbacks, scaffolds containing safer, cheaper, and more effective bioactive molecules, combined with stem cells and topographical cues, remain a promising alternative for clinical use to treat CSDs in the CMF complex replacing autografts and allografts.

The bone morphogenetic protein (BMP) signaling pathway plays a crucial role in bone development and regeneration. While BMP-2 is widely used as an alternative to autograft, its clinical application has raised concerns about adverse side effects and deteriorated bone quality. Therefore, there is a need to develop more sophisticated approaches to regulate BMP signaling and promote bone regeneration. Here, we present a novel complementary strategy that targets both BMP antagonist noggin and agonist Trb3 to enhance bone defect repair without the application of exogenous BMP-2. In vitro studies showed that overexpression of Trb3 with simultaneous noggin suppression significantly promotes osteogenic differentiation of mesenchymal stem cells. This was accompanied by increased BMP/Smad signaling. We also developed sterosome nanocarriers, a non-phospholipid liposomal system, to achieve non-viral mediated noggin suppression and Trb3 overexpression. The gene-loaded sterosomes were integrated onto an apatite-coated polymer scaffold for in vivo calvarial defect implantation, resulting in robust bone healing compared to BMP-2 treatments. Our work provides a promising alternative for high-quality bone formation by regulating expression of BMP agonists and antagonists.

Critical-sized bone defects are a reconstructive challenge, particularly in the craniomaxillofacial (CMF) skeleton. The "gold standard" of autologous bone grafting has been the work horse of reconstruction in both congenital and acquired defects of CMF skeleton. Autologous bone has the proper balance of the protein (or organic) matrix and mineral components with no immune response. Organic and mineral adjuncts exist that offer varying degrees of osteogenic, osteoconductive, osteoinductive, and osteostimulative properties needed for treatment of critical-sized defects. In this review, we discuss the various mostly organic and mostly mineral bone graft substitutes available for autologous bone grafting. Primarily organic bone graft substitutes/enhancers, including bone morphogenic protein, platelet-rich plasma, and other growth factors, have been utilized to support de novo bone growth in setting of critical-sized bone defects. Primarily mineral options, including various calcium salt formulation (calcium sulfate/phosphate/apatite) and bioactive glasses have been long utilized for their similar composition to bone. Yet, a bone graft substitute that can supplant autologous bone grafting is still elusive. However, case-specific utilization of bone graft substitutes offers a wider array of reconstructive options.

Background  The outcome of alveolar grafting with synthetic bone substitute (Osteon III) in various bone defect volumes is highlighted. Methods  A prospective study was accomplished on 55 patients (6-13 years of age) with unilateral alveolar bone cleft. Osteon III, consisting of hydroxyapatite and tricalcium phosphate, is used to reconstruct the defect. Alveolus defect diameter was calculated before surgery (V1), after 3 months (V2), and finally after 6 months (V3) postsurgery. In the t -test, a significant difference and correlation between V1, V2, and V3 are stated. A p- value of 0.01 is considered a significant difference between parameters. Results  The degree of cleft is divided into three categories: small (9 cases), medium (20 patients), and large (26 cases).The bone volume of the clefted site is divided into three steps: volume 1: (mean 18.1091 mm 3 ); step 2: after 3 months, volume 2 resembles the amount of unhealed defect (mean 0.5109 mm 3 ); and the final bone volume assessment is made after 6 months (22.5455 mm 3 ). Both show statistically significant differences in bone volume formation. Conclusion  An alloplastic bone substitute can also be used as a graft material because of its unlimited bone retrieval. Osteon III can be used to reconstruct the alveolar cleft smoothly and effectively.

Electrical stimulation (EStim), whether used alone or in combination with bone tissue engineering (BTE) approaches, has been shown to promote bone healing. In our previous in vitro studies, mesenchymal stem cells (MSCs) were exposed to EStim and a sustained, long-lasting increase in osteogenic activity was observed. Based on these findings, we hypothesized that pretreating MSC with EStim, in 2D or 3D cultures, before using them to treat large bone defects would improve BTE treatments. Critical size femur defects were created in 120 Sprague-Dawley rats and treated with scaffold granules seeded with MSCs that were pre-exposed or not (control group) to EStim 1 h/day for 7 days in 2D (MSCs alone) or 3D culture (MSCs + scaffolds). Bone healing was assessed at 1, 4, and 8 weeks post-surgery. In all groups, the percentage of new bone increased, while fibrous tissue and CD68+ cell count decreased over time. However, these and other healing features, like mineral density, bending stiffness, the amount of new bone and cartilage, and the gene expression of osteogenic markers, did not significantly differ between groups. Based on these findings, it appears that the bone healing environment could counteract the long-term, pro-osteogenic effects of EStim seen in our in vitro studies. Thus, EStim seems to be more effective when administered directly and continuously at the defect site during bone healing, as indicated by our previous studies.

Oxygen is critical to the survival, function and fate of mammalian cells. Oxygen tension controls cellular behavior through metabolic programming, which in turn controls tissue regeneration. A variety of biomaterials with oxygen-releasing capabilities have been developed to provide oxygen supply to ensure cell survival and differentiation for therapeutic efficacy, and to prevent hypoxia-induced tissue damage and cell death. However, controlling the oxygen release with spatial and temporal accuracy is still technically challenging. In this review, we provide a comprehensive overview of organic and inorganic materials available as oxygen sources, including hemoglobin-based oxygen carriers (HBOCs), perfluorocarbons (PFCs), photosynthetic organisms, solid and liquid peroxides, and some of the latest materials such as metal-organic frameworks (MOFs). Additionally, we introduce the corresponding carrier materials and the oxygen production methods and present state-of-the-art applications and breakthroughs of oxygen-releasing materials. Furthermore, we discuss the current challenges and the future perspectives in the field. After reviewing the recent progress and the future perspectives of oxygen-releasing materials, we predict that smart material systems that combine precise detection of oxygenation and adaptive control of oxygen delivery will be the future trend for oxygen-releasing materials in regenerative medicine.

In this review, we explore the application of novel biomaterial-based therapies specifically targeted towards craniofacial bone defects. The repair and regeneration of critical sized bone defects in the craniofacial region requires the use of bioactive materials to stabilize and expedite the healing process. However, the existing clinical approaches face challenges in effectively treating complex craniofacial bone defects, including issues such as oxidative stress, inflammation, and soft tissue loss. Given that a significant portion of individuals affected by traumatic bone defects in the craniofacial area belong to the aging population, there is an urgent need for innovative biomaterials to address the declining rate of new bone formation associated with age-related changes in the skeletal system. This article emphasizes the importance of semiconductor industry-derived materials as a potential solution to combat oxidative stress and address the challenges associated with aging bone. Furthermore, we discuss various material and autologous treatment approaches, as well as in vitro and in vivo models used to investigate new therapeutic strategies in the context of craniofacial bone repair. By focusing on these aspects, we aim to shed light on the potential of advanced biomaterials to overcome the limitations of current treatments and pave the way for more effective and efficient therapeutic interventions for craniofacial bone defects.

There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue. Three-dimensional (3D) printing offers a method of fabricating complex anatomical features of clinically relevant sizes. However, the construction of a scaffold to replicate the complex hierarchical structure of natural tissues remains challenging. This paper reports a novel biofabrication method that is capable of creating intricately designed structures of anatomically relevant dimensions. The beneficial properties of the electrospun fibre meshes can finally be realised in 3D rather than the current promising breakthroughs in two-dimensional (2D). The 3D model was created from commercially available computer-aided design software packages in order to slice the model down into many layers of slices, which were arrayed. These 2D slices with each layer of a defined pattern were laser cut, and then successfully assembled with varying thicknesses of 100 μm or 200 μm. It is demonstrated in this study that this new biofabrication technique can be used to reproduce very complex computer-aided design models into hierarchical constructs with micro and nano resolutions, where the clinically relevant sizes ranging from a simple cube of 20 mm dimension, to a more complex, 50 mm-tall human ears were created. In-vitro cell-contact studies were also carried out to investigate the biocompatibility of this hierarchal structure. The cell viability on a micromachined electrospun polylactic-co-glycolic acid fibre mesh slice, where a range of hole diameters from 200 μm to 500 μm were laser cut in an array where cell confluence values of at least 85% were found at three weeks. Cells were also seeded onto a simpler stacked construct, albeit made with micromachined poly fibre mesh, where cells can be found to migrate through the stack better with collagen as bioadhesives. This new method for biofabricating hierarchical constructs can be further developed for tissue repair applications such as maxillofacial bone injury or nose/ear cartilage replacement in the future.

This study assessed the effect of platelet-rich plasma (PRP) on the clinical success of alveolar grafts in patients with cleft lip and palate.

In this meta-analysis, a search of the literature was conducted in Medline, Scopus, ISI Web of Science, and Cochrane Central Register of Controlled Trials for randomized clinical trials using PRP or platelet-rich fibrin (PRF) along with autogenous bone for alveolar ridge grafts in patients with cleft lip and palate. The methodological quality of the studies was analyzed using Cochrane's risk of the bias assessment tool. The extracted data underwent meta-analysis using the random-effects model.

Of a total of 2256 articles retrieved, 12 met the eligibility criteria and were enrolled; out of which 6 did not undergo meta-analysis due to heterogeneous data. The percentage of defects filled by bone graft was 0.648% (95% confidence interval: -0.15 to 1.45), which was not statistically significant ( P =0.115). Subgroup analysis showed no significant difference based on the use of PRF or PRP ( P =0.28), type of cleft (unilateral/bilateral; P =0.56), or type of radiographic modality (3D/2D; P =0.190). Meta-regression analysis showed that the duration of follow-up and the difference in the mean age of patients did not have a significant effect on the results (R=0, I2: high).

The application of PRP/PRF in combination with autogenous bone graft did not have a significant effect on the percentage of alveolar cleft filled by a bone graft. Future clinical studies are required to further elucidate the effect of PRP in the regeneration of alveolar clefts.

Large oral bone defects require grafting of bone blocks rather than granules to give physically robust, biocompatible and osteoconductive regeneration. Bovine bone is widely accepted as a source of clinically appropriate xenograft material. However, the manufacturing process often results in both reduced mechanical strength and biological compatibility. The aim of this study was to assess bovine bone blocks at different sintering temperatures and measure the effects on mechanical properties and biocompatibility. Bone blocks were divided into four groups; Group 1: Control (Untreated); Group 2: Initial boil for 6 h; Group 3: Boil 6 h followed by sintering at 550 °C for 6 h; Group 4: Boil 6 h followed by sintering at 1100 °C for 6 h. Samples were assessed for their purity, crystallinity, mechanical strength, surface morphology, chemical composition, biocompatibility and clinical handling properties. Statistical analysis was performed using one-way ANOVA and post-hoc Tukey's tests for normally distributed and Friedman test for abnormally distributed quantitative data from compression tests and PrestoBlue™ metabolic activity tests. The threshold for statistical significance was set at p < 0.05. The results showed that higher temperature sintering (Group 4) removed all organic material (0.02% organic components and 0.02% residual organic components remained) and increased crystallinity (95.33%) compared to Groups 1-3. All test groups (Group 2-4) showed decreased mechanical strength (MPa: 4.21 ± 1.97, 3.07 ± 1.21, 5.14 ± 1.86, respectively) compared with raw bone (Group 1) (MPa: 23.22 ± 5.24, p <0.05), with micro-cracks seen under SEM in Groups 3 and 4. Group 4 had the highest biocompatibility (p < 0.05) with osteoblasts as compared to Group 3 at all time points in vitro. Clinical handling tests indicated that Group 4 samples could better withstand drilling and screw placement but still demonstrated brittleness compared to Group 1. Hence, bovine bone blocks sintered at 1100 °C for 6 h resulted in highly pure bone with acceptable mechanical strength and clinical handling, suggesting it is a viable option as a block grafting material.

Disorders of bone integrity carry a high global disease burden, frequently requiring intervention, but there is a paucity of methods capable of noninvasive real-time assessment. Here we show that miniaturized handheld near-infrared spectroscopy (NIRS) scans, operated via a smartphone, can assess structural human bone properties in under three seconds. A hand-held NIR spectrometer was used to scan bone samples from 20 patients and predict: bone volume fraction (BV/TV); and trabecular (Tb) and cortical (Ct) thickness (Th), porosity (Po), and spacing (Sp). NIRS scans on both the inner (trabecular) surface or outer (cortical) surface accurately identified variations in bone collagen, water, mineral, and fat content, which then accurately predicted bone volume fraction (BV/TV, inner R2 = 0.91, outer R2 = 0.83), thickness (Tb.Th, inner R2 = 0.9, outer R2 = 0.79), and cortical thickness (Ct.Th, inner and outer both R2 = 0.90). NIRS scans also had 100% classification accuracy in grading the quartile of bone thickness and quality. We believe this is a fundamental step forward in creating an instrument capable of intraoperative real-time use.

Existing bone tissue engineering strategies aim to achieve minimize surgical trauma, stabilize the injured area, and establish a dynamic osteogenic microenvironment. The cutting-edge bone glue developed in this study satisfies these criteria. Inspired by the excellent adhesive properties of mussels, herein, a super osteogenic glue (L-DPZ) that integrates poly(vinyl alcohol), L-dopa amino acid, and zeolitic imidazolate framework-8 characterized by catechol-metal coordination is used to successfully adhere to hard tissue with a maximum adhesive strength of 10 MPa, which is much higher than those of commercial and previously reported bone glues. The stable hard tissue adhesion also enables it to adhere strongly to luxated or broken teeth, Bio-Oss (a typical bone graft material), and splice fragments from comminuted fractures of the rabbit femur. Then, it is testified that the L-DPZ hydrogels exhibit satisfactory biocompatibility, stable degradability, and osteogenic ability in vitro. Moreover, the ability to anchor Bio-Oss and sustained osteogenesis of L-DPZ result in satisfactory healing in calvarial bone defect models in rabbits, as observed by increased bone thickness and the ingrowth of new bone tissue. These results are expected to demonstrate solutions to clinical dilemmas such as comminuted bone fracture fixation, bone defect reconstruction, and teeth dislocation replantation.

The current review aimed to assess the reliability and efficacy of tissue-engineered composite grafts in the reconstruction of large maxillofacial defects resulting from trauma or a benign pathologic disease. A systematic review of the literature was conducted using PubMed/Medline, Embase, and Scopus up to March 2022. The eligibility criteria included patients who had been treated with composite allogeneic tissue engineering for immediate/delayed reconstruction of large maxillofacial defects with minimum/no bone harvesting site. In the initial search, 2614 papers were obtained, and finally, 13 papers were eligible to be included in the current study. Most included papers were case reports or case series. A total of 144 cases were enrolled in this systematic review. The mean age of the patients was 43.34 (age range: 9-89). Most studies reported a successful outcome. Bone tissue engineering for the reconstruction and regeneration of crucial-sized maxillofacial defects is an evolving science still in its infancy. In conclusion, this review paper and the current literature demonstrate the potential for using large-scale transplantable, vascularized, and customizable bone with the aim of reconstructing the large maxillofacial bony defects in short-term follow-ups.

Bacterial infection associated with bone grafts is one of the major challenges that can lead to implant failure. Treatment of these infections is a costly endeavor; therefore, an ideal bone scaffold should merge both biocompatibility and antibacterial activity. Antibiotic-impregnated scaffolds may prevent bacterial colonization but exacerbate the global antibiotic resistance problem. Recent approaches combined scaffolds with metal ions that have antimicrobial properties. In our study, a unique strontium/zinc (Sr/Zn) co-doped nanohydroxyapatite (nHAp) and Poly (lactic-co-glycolic acid) -(PLGA) composite scaffold was fabricated using a chemical precipitation method with different ratios of Sr/Zn ions (1%, 2.5%, and 4%). The scaffolds' antibacterial activity against Staphylococcus aureus were evaluated by counting bacterial colony-forming unit (CFU) numbers after direct contact with the scaffolds. The results showed a dose-dependent reduction in CFU numbers as the Zn concentration increased, with 4% Zn showing the best antibacterial properties of all the Zn-containing scaffolds. PLGA incorporation in Sr/Zn-nHAp did not affect the Zn antibacterial activity and the 4% Sr/Zn-nHAp-PLGA scaffold showed a 99.7% bacterial growth inhibition. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay showed that Sr/Zn co-doping supported osteoblast cell proliferation with no apparent cytotoxicity and the highest doping percentage in the 4% Sr/Zn-nHAp-PLGA was found to be ideal for cell growth. In conclusion, these findings demonstrate the potential for a 4% Sr/Zn-nHAp-PLGA scaffold with enhanced antibacterial activity and cytocompatibility as a suitable candidate for bone regeneration.

Craniofacial reconstruction requires robust bone of specified geometry for the repair to be both functional and aesthetic. While native bone from elsewhere in the body can be harvested, shaped, and implanted within a defect, using either an in vitro or in vivo bioreactors eliminates donor site morbidity while increasing the customizability of the generated tissue. In vitro bioreactors utilize cells harvested from the patient, a scaffold, and a device to increase mass transfer of nutrients, oxygen, and waste, allowing for generation of larger viable tissues. In vivo bioreactors utilize the patient's own body as a source of cells and of nutrient transfer and involve the implantation of a scaffold with or without growth factors adjacent to vasculature, followed by the eventual transfer of vascularized, mineralized tissue to the defect site. Several different models of in vitro bioreactors exist, and several different implantation sites have been successfully utilized for in vivo tissue generation and defect repair in humans. In this review, we discuss the specifics of each bioreactor strategy, as well as the advantages and disadvantages of each and the future directions for the engineering of bony tissues for craniofacial defect repair.

Bones damaged due to disease or accidents can be repaired in different ways. Tissue engineering has helped with scaffolds made of different biomaterials and various methods. Although all kinds of biomaterials can be useful, sometimes their weakness in cellular activity or osteoconductivity prevents their optimal use in the fabrication of bone scaffolds. To solve this problem, we need additional processes, such as surface modification. One of the common methods is coating with polydopamine. Polydopamine can not only cover the weakness of the scaffolds in terms of cellular properties, but it can also create or increase osteoconductivity properties. Polydopamine creates a hydrophilic layer on the surface of scaffolds due to a large number of functional groups such as amino and hydroxyl groups. This layer allows bone cells to anchor and adheres well to the surfaces. In addition, it creates a biocompatible environment for proliferation and differentiation. Besides, the polydopamine coating makes the surfaces chemically active by catechol and amine group, and as a result of their presence, osteoconductivity increases. In this mini-review, we investigated the characteristics, structure, and properties of polydopamine as a modifier of bone substitutes. Finally, we evaluated the cell adhesion and osteoconductivity of different polydopamine-modified bone scaffolds.

To reconstruct and rehabilitate a severely atrophied mandible. Case presentation. A 40-year-old female patient with the chief complaint of denture instability was admitted to our care. In our opinion, the optimum reconstructive method for their severely atrophied mandible (width of 4 mm) was bone grafting with an inverted sandwich technique. 2 split-thickness autogenous calvarial grafts were attained. 4 onlay bone blocks were prepared, placed with an inverted sandwich technique, and fixed with 8 lag screws. 4 implants (Osstem, ⌀4×10 mm) were placed simultaneously, and an immediate post-operation cone beam computed tomography confirmed the proper placement of the grafts and implants. No complications were reported within 4 and 8 months following graft and implant placement. Final impressions for full dental rehabilitation were taken at the 8-month follow-up.

Split-thickness calvarial grafts and simultaneous implant placement seem to be a very efficient and promising approach for major reconstruction of the mandible. However, further studies are recommended.

Bone substitute materials have been successfully used for bone defects in orthopedics and trauma surgery for a long time; however, there are cases, especially in bone defects with a critical size, in which the treatment is complicated. Nowadays, multiple bone substitute materials are available. Autologous cancellous bone grafts remain the gold standard among the bone replacement materials; however, donor site morbidity and the limited availability of autologous cancellous bone represent restrictions for autologous bone grafting. Allogeneic cancellous bone grafts have also been successfully for years in the treatment of bone defects; however, infection rates of more than 10% have been described for the use of allogeneic cancellous bone. By introducing synthetic bone substitutes further alternatives are currently available to the user for the individual treatment of bone defects. The aim of this study is to demonstrate the advantages and disadvantages of various synthetic bone substitute materials.

Various techniques for tissue engineering have been introduced to help regenerate damaged or lost bone tissue. This study aimed to see the potential implication of platelet-rich fibrin (PRF) to accelerate the bone healing process in rat bone defects.

A systematic literature search was conducted from several electronic databases on subjects looking at the use of PRF in rat bone defects and their results in bone regeneration. Specific results compared PRF vs. other methods, PRF vs. control, and PRV vs. combination PRF and other methods. Science Direct, PubMed, and Cochrane Library were the main information sources. The Cochrane Collaboration method is employed to assess the risk of bias.

A total of 483 rats were used in the twelve studies, and this meta-analysis showed that the PRF vs. other methods pooled odds ratio (OR) obtained was 0.92 (95% CI 0.42-2.04; p = 0.29; I2 = 18%), PRF versus control OR obtained 9.45 (95% CI 4.68-19.08; P = 0.01; I2 = 0%), the combination of PRF compared to PRF alone OR obtained 0.12 (95% CI 0.03-0.41; p = 0.01; I2 = 0%).

Platelet-rich fibrin accelerates the bone healing process in rat bone defects compared to physiologically. Platelet-rich fibrin combined with other methods can stimulate rat bone defects than utilization of platelet-rich fibrin only. The small number of articles assessed may cause limitations in sensitivity tests. This study was registered in the research registry (reviewregistry1341).

Cranial bone loss presents a major clinical challenge and new regenerative approaches to address craniofacial reconstruction are in great demand. Induced pluripotent stem cell (iPSC) differentiation is a powerful tool to generate mesenchymal stromal cells (MSCs). Prior research demonstrated the potential of bone marrow-derived MSCs (BM-MSCs) and iPSC-derived mesenchymal progenitor cells via the neural crest (NCC-MPCs) or mesodermal lineages (iMSCs) to be promising cell source for bone regeneration. Overexpression of human recombinant bone morphogenetic protein (BMP)6 efficiently stimulates bone formation. The study aimed to evaluate the potential of iPSC-derived cells via neural crest or mesoderm overexpressing BMP6 and embedded in 3D printable bio-ink to generate viable bone graft alternatives for cranial reconstruction. Cell viability, osteogenic potential of cells, and bio-ink (Ink-Bone or GelXa) combinations were investigated in vitro using bioluminescent imaging. The osteogenic potential of bio-ink-cell constructs were evaluated in osteogenic media or nucleofected with BMP6 using qRT-PCR and in vitro μCT. For in vivo testing, two 2 mm circular defects were created in the frontal and parietal bones of NOD/SCID mice and treated with Ink-Bone, Ink-Bone + BM-MSC-BMP6, Ink-Bone + iMSC-BMP6, Ink-Bone + iNCC-MPC-BMP6, or left untreated. For follow-up, µCT was performed at weeks 0, 4, and 8 weeks. At the time of sacrifice (week 8), histological and immunofluorescent analyses were performed. Both bio-inks supported cell survival and promoted osteogenic differentiation of iNCC-MPCs and BM-MSCs in vitro. At 4 weeks, cell viability of both BM-MSCs and iNCC-MPCs were increased in Ink-Bone compared to GelXA. The combination of Ink-Bone with iNCC-MPC-BMP6 resulted in an increased bone volume in the frontal bone compared to the other groups at 4 weeks post-surgery. At 8 weeks, both iNCC-MPC-BMP6 and iMSC-MSC-BMP6 resulted in an increased bone volume and partial bone bridging between the implant and host bone compared to the other groups. The results of this study show the potential of NCC-MPC-incorporated bio-ink to regenerate frontal cranial defects. Therefore, this bio-ink-cell combination should be further investigated for its therapeutic potential in large animal models with larger cranial defects, allowing for 3D printing of the cell-incorporated material.

This study aims to compare the effect of demineralized xenogeneic tooth graft in its two forms, particulate and block, with bovine xenograft in the healing of a rabbit tibial bone defect model.

Two monocortical bony defects were made in the right tibias of 36 rabbits, and were divided into four groups. Group I defects were left empty, while group II, III, and IV were filled with bovine xenograft, demineralized particulate tooth graft, and demineralized perforated block tooth graft, respectively for evaluation of the bone healing process. Three rabbits from each group were euthanized at 2, 4, and 6 weeks after surgery. The bone specimens were processed and stained with hematoxylin and eosin (H&E) and osteopontin (OPN) immunohistochemical staining. The results were subjected to image analysis and quantitative evaluation.

Demineralized particulate tooth graft showed the best bone healing capacity compared to all other groups at all time points tested, as it showed a large amount of the formed bone, rapid closure of the defect with a significant increase in OPN expression, and the least amount of the residual grafted particles.

In comparison to bovine xenograft and demineralized dentin block graft, the demineralized particulate tooth grafting material is a promising bone grafting substitute as it proved to be osteoconductive, biocompatible, and bioresorbable.

Demineralized tooth grafting material can aid in the regeneration of large bone defects, leading to improvement in the filling of the bone defects which can help in oral and maxillofacial reconstruction.

The purpose is to describe a technique of using ramal bone graft for reconstructing defects of the infra-orbital rim (IOR), assess outcomes and complications. This was a retrospective chart review of 16 patients who underwent ramal bone grafting for IOR fractures. Outcomes evaluated were improvement in clinical findings (lid/globe malposition, tethering of facial skin and implant extrusion) and complications. Data analysis included descriptive statistics. The sample included 15 males and 1 female, with a mean age of 31.6 years. Lid malposition, globe malposition and tethering of facial skin was seen in 16, 13 and 6 patients, respectively. One patient demonstrated extrusion of implant. The mean size of bone harvested was 14 × 7 mm. All patients demonstrated improved globe position post-treatment, while 3 had residual lid retraction. Two patients demonstrated wound dehiscence in the donor site. In conclusion ramal bone graft was found to be a viable alternative for IOR reconstruction.

Biomaterials and biotechnology are becoming increasingly important fields in modern medicine. For cranial bone defects of various aetiologies, artificial materials, such as poly-methyl-methacrylate, are often used. We report our clinical experience with poly-methyl-methacrylate for a novel in vivo bone defect closure and artificial bone flap development in various neurosurgical operations.

The experimental study included 12 patients at a single centre in 2018. They presented with cranial bone defects after various neurosurgical procedures, including tumour, traumatic brain injury and vascular pathologies. The patients underwent an in vivo bone reconstruction from poly-methyl-methacrylate, which was performed immediately after the tumour removal in the tumour group, whereas the trauma and vascular patients required a second surgery for cranial bone reconstruction due to the bone decompression. The artificial bone flap was modelled in vivo just before the skin closure. Clinical and surgical data were reviewed.

All patients had significant bony destruction or unusable bone flap. The tumour group included five patients with meningiomas destruction and the trauma group comprised four patients, all with severe traumatic brain injury. In the vascular group, there were three patients. The average modelling time for the artificial flap modelling was approximately 10 min. The convenient location of the bone defect enabled a relatively straightforward and fast reconstruction procedure. No deformations of flaps or other complications were encountered, except in one patient, who suffered a postoperative infection.

Poly-methyl-methacrylate can be used as a suitable material to deliver good cranioplasty cosmesis. It offers an optimal dural covering and brain protection and allows fast intraoperative reconstruction with excellent cosmetic effect during the one-stage procedure. The observations of our study support the use of poly-methyl-methacrylate for the ad hoc reconstruction of cranial bone defects.

Severe congenital mandibular hypoplasia may cause significant upper airway obstruction, often necessitating immediate tracheostomy. Recent surgical advances have demonstrated early intervention with mandibular distraction osteogenesis over tracheostomy may yield desirable aesthetic and functional outcomes. Here we present a case of bilateral mandibular hypoplasia, severe on the right and mild on the left, secondary to Goldenhar syndrome yielding significant tongue-based upper airway obstruction that was surgically corrected with mandibular bone allograft reconstruction of the right condyle, ramus, and posterior half of the mandibular body. Postoperative polysomnography revealed significantly improved obstructive apnea and computed tomography demonstrated adequate placement of the bone allograft to overcorrect the affected hemi-mandible. To the authors' knowledge, this is the first report of immediate mandibular allografting alleviating tongue-based upper airway obstruction secondary to mandibular hypoplasia in an infant. Mandibular bone allografting may be a favorable alternative to immediate tracheostomy with delayed surgical intervention, though long-term follow up is needed to assess graft durability and maintenance of airway patency.

Decompressive craniectomy (DC) is effective in controlling increasing intracranial pressure determined by a wide range of conditions, mainly traumatic brain injury (TBI) and stroke, and the subsequent cranioplasty (CP) displays potential therapeutic benefit in terms of overall neurological function. While autologous bone flap (ABF) harvested at the time of DC is the ideal material for skull defect reconstruction, it carries several risks. Aseptic bone flap resorption (BFR) is one of the most common complications, often leading to surgical failure. The aim of our study was to systematically review the literature and carry out a meta-analysis of possible factors involved in BFR in patients undergoing ABF cranioplasty after DC. A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. Different medical databases (PubMed, Embase, and Scopus) were screened for eligible scientific reports until April 30th 2021. The following data were collected for meta-analysis to assess their role in BFR: sex, age, the interval time between DC and CP, the presence of systemic factors, the etiology determining the DC, CP surgical time, CP features, VP shunt placement, CP infection. Studies including pediatric patients or with less than 50 patients were excluded. Fifteen studies were included. There was a statistically significant increased incidence of BFR in patients with CPF > 2 compared to patients with CPF ≤ 2 (54.50% and 22.76% respectively, p = 0.010). TBI was a significantly more frequent etiology in the BFR group compared to patients without BFR (61.95% and 47.58% respectively, p < 0.001). Finally, patients with BFR were significantly younger than patients without BFR (39.12 ± 15.36 years and 47.31 ± 14.78 years, respectively, p < 0.001). The funnel plots were largely symmetrical for all the studied factors. Bone flap fragmentation, TBI etiology, and young age significantly increase the risk of bone resorption. Further studies are needed to strengthen our results and to clarify if, in those cases, a synthetic implant for primary CP should be recommended.

Trauma-induced, critical-size bone defects pose a clinical challenge to heal. Albeit autografts are the standard-of-care, they are limited by their inability to be shaped to various defect geometries and often incur donor site complications. Herein, the combination of a "self-fitting" shape memory polymer (SMP) scaffold and seeded mesenchymal stromal cells (MSCs) was investigated as an alternative. The porous SMP scaffold, prepared from poly(ε-caprolactone) diacrylate (PCL-DA) and coated with polydopamine, provided conformal shaping and cell adhesion. MSCs from five tissues, amniotic (AMSCs), chorionic tissue (CHSCs), umbilical cord (UCSCs), adipose (ADSCs), and bone marrow (BMSCs) were evaluated for viability, density, and osteogenic differentiation on the SMP scaffold. BMSCs exhibited the fastest increase in cell density by day 3, but after day 10, CHSCs, UCSCs, and ADSCs approached similar cell density. BMSCs also showed the greatest calcification among the cell types, followed closely by ADSCs, CHSCs and AMSCs. Alkaline phosphatase (ALP) activity peaked at day 7 for AMSCs, UCSCs, ADSCs and BMSCs, and at day 14 for CHSCs, which had the greatest overall ALP activity. Of all the cell types, only scaffolds cultured with ADSCs in osteogenic media had increased hardness and local modulus as compared to blank scaffolds after 21 days of cell culture and osteogenic differentiation. Overall, ADSCs performed most favorably on the SMP scaffold. The SMP scaffold was able to support key cellular behaviors of MSCs and could potentially be a viable, regenerative alternative to autograft.

Successful implant dentistry can be directly related to the quality and quantity of bone at the recipient site of the implant. Over the years, bone grafts have been used for the treatment of various osseous defects. Due to the widespread acceptance of dental implants, interest in bone reconstruction for the oral cavity has increased dramatically over the past decade. Many patients who request implant rehabilitation require ancillary procedures to increase the quantity and quality of the recipient's bone. The internal architecture of the bone is generally described in terms of quality of the bone, which in turn reflects the strength (degree of compactness) of the bone. This is considered a crucial factor about the available bone at the edentulous site while planing about the design of the planned implant, surgical approach, healing time, and the initial progressive bone loading during the prosthetic reconstruction. Atrophy of the alveolar processes is expressed as a reduction of height and width. Databases were electronically searched up to April 2019 to identify human bone graft studies to provide contemporary and comprehensive information about the various bone grafts used in dental implant management.