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Treatment of bone defects resulting after tumor surgeries, accidents, or non-unions is an actual problem linked to morbidity and the necessity of a second surgery and often requires a critical healthcare cost. Although the surgical technique has changed in a modern way, the treatment outcome is still influenced by patient age, localization of the bone defect, associated comorbidities, the surgeon approach, and systemic disorders. Three-dimensional magnesium-based scaffolds are considered an important step because they can have precise bone defect geometry, high porosity grade, anatomical pore shape, and mechanical properties close to the human bone. In addition, magnesium has been proven in in vitro and in vivo studies to influence bone regeneration and new blood vessel formation positively. In this review paper, we describe the magnesium alloy's effect on bone regenerative processes, starting with a short description of magnesium's role in the bone healing process, host immune response modulation, and finishing with the primary biological mechanism of magnesium ions in angiogenesis and osteogenesis by presenting a detailed analysis based on a literature review. A strategy that must be followed when a patient-adapted scaffold dedicated to bone tissue engineering is proposed and the main fabrication technologies are combined, in some cases with artificial intelligence for Mg alloy scaffolds, are presented with examples. We emphasized the microstructure, mechanical properties, corrosion behavior, and biocompatibility of each study and made a basis for the researchers who want to start to apply the regenerative potential of magnesium-based scaffolds in clinical practice. Challenges, future directions, and special potential clinical applications such as osteosarcoma and persistent infection treatment are present at the end of our review paper. [ABSTRACT FROM AUTHOR]

Black Phosphorus (BP) is a new semiconductor material with excellent biocompatibility, degradability, and optical and electrophysical properties. A growing number of studies show that BP has high potential applications in the biomedical field. This article aims to systematically review the research progress of BP composite medical materials in the field of tissue engineering, mining BP in bone regeneration, skin repair, nerve repair, inflammation, treatment methods, and the application mechanism. Furthermore, the paper discusses the shortcomings and future recommendations related to the development of BP. These shortcomings include stability, photothermal conversion capacity, preparation process, and other related issues. However, despite these challenges, the utilization of BP-based medical materials holds immense promise in revolutionizing the field of tissue repair. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HA)-based materials are widely used in the bone defect restoration field due to their stable physical properties, good biocompatibility, and bone induction potential. To further improve their performance with extra functions such as antibacterial activity, various kinds of metal ion-doped HA-based materials have been proposed and synthesized. This paper offered a comprehensive review of metal ion-doped HA-based materials for bone defect restoration based on the introduction of the physicochemical characteristics of HA followed by the synthesis methods, properties, and applications of different kinds of metal ion (Ag+, Zn2+, Mg2+, Sr2+, Sm3+, and Ce3+)-doped HA-based materials. In addition, the underlying challenges for bone defect restoration using these materials and potential solutions were discussed. [ABSTRACT FROM AUTHOR]

Bones play an important role in maintaining exercise and protecting organs. Bone defect, as a common orthopedic disease in clinics, can cause tremendous damage with long treatment cycles. Therefore, the treatment of bone defect remains as one of the main challenges in clinical practice. Today, with increased incidence of bone disease in the aging population, demand for bone repair material is high. At present, the method of clinical treatment for bone defects including non-invasive therapy and invasive therapy. Surgical treatment is the most effective way to treat bone defects, such as using bone grafts, Masquelet technique, Ilizarov technique etc. In recent years, the rapid development of tissue engineering technology provides a new treatment strategy for bone repair. This review paper introduces the current situation and challenges of clinical treatment of bone defect repair in detail. The advantages and disadvantages of bone tissue engineering scaffolds are comprehensively discussed from the aspect of material, preparation technology, and function of bone tissue engineering scaffolds. This paper also summarizes the 3D printing technology based on computer technology, aiming at designing personalized artificial scaffolds that can accurately fit bone defects. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study is to review the available information on the use of avian eggshell as bone regeneration material. Five databases were searched up to October 2020. Animal studies with a bone defect model using eggshell as a grafting material were included. Risk of bias and the quality of the papers were assessed. Overall, a total of 581 studies were included in the study, 187 after duplicate removal. Using the inclusion and exclusion criteria 167 records were further excluded. The full text of the remaining 20 articles was assessed for eligibility and included in the review. There were different methods of obtaining eggshell for grafting purposes. Eggshell is a biocompatible grafting material, with bone formation capabilities. It forms new bone similar to other products currently in use in clinical practice. It can be combined with other materials to enhance its proprieties. Eggshell is a promising biomaterial to be used in bone grafting procedures, though further research is needed. The aim of this study is to systemically review the available evidence on the in vivo behavior of eggshell as a guided bone regeneration substitute material. Five databases (PubMed, Cochrane, Web of Science, Scopus, EMBASE) were searched up to October 2020. In vivo animal studies with a bone defect model using eggshell as a grafting material were included. Risk of bias was assessed using SYRCLE tool and the quality assessment using the ARRIVE guidelines. Overall, a total of 581 studies were included in the study, 187 after duplicate removal. Using the inclusion and exclusion criteria 167 records were further excluded. The full text of the remaining 20 articles was assessed for eligibility and included in the qualitative and quantitative assessment synthesis. There were different methods of obtaining eggshell grafting materials. Eggshell is a biocompatible grafting material, with osteoconduction proprieties. It forms new bone similar to Bio-Oss and demineralized freeze-dried bone matrix. It can be combined with other materials to enhance its proprieties. Due to the high variability of the procedures, animals, production and assessment methods, no meta-analysis could be performed. Eggshell might be considered a promising biomaterial to be used in bone grafting procedures, though further research is needed. [ABSTRACT FROM AUTHOR]

The aim of this scoping review is to analyse the biological effects of the orthodontic tooth movement (OTM) in areas with bone defects that are undergoing regeneration using different types of regenerative materials and techniques. The electronic research was performed on four databases as follows: PubMed, Scopus, EMBASE, and Web of Science. Data were extracted according to publication information, study design, sample characteristics, parameters of OTM, biological repercussions on the periodontium complex, methods of analysis, and conclusions. A total of thirty studies were included in the final review. In twenty-two studies, the most widely adopted grafting materials were alloplastics. In most studies, the orthodontic force used was 10 or 100 g, and the timing of application ranged from immediate to 6 months after grafting surgery. Twenty-four studies showed an increase in osteogenesis; in five studies, the clinical attachment level (CAL) increased; in five others, the probing pocket depth (PPD) decreased; in sixteen studies, there was root resorption of a different magnitude. Though the effects of OTM on the periodontium in the grafted areas were positive, the outcomes should be interpreted with caution as future preclinical and clinical studies are needed to extrapolate more valid conclusions. [ABSTRACT FROM AUTHOR]

Limitations of bone defect reconstruction include poor bone healing and osteointegration with acrylic cements, lack of strength with bone putty/paste, and poor osteointegration. Tissue engineering aims to bridge these gaps through the use of bioactive implants. However, there is often a risk of infection and biofilm formation associated with orthopedic implants, which may develop anti-microbial resistance. To promote bone repair while also locally delivering therapeutics, 3D-printed implants serve as a suitable alternative. Soft, nanoporous 3D-printed filaments made from a thermoplastic polyurethane and polyvinyl alcohol blend, LAY-FOMM and LAY-FELT, have shown promise for drug delivery and orthopedic applications. Here, we compare 3D printability and sustained antibiotic release kinetics from two types of commercial 3D-printed porous filaments suitable for bone tissue engineering applications. We found that both LAY-FOMM and LAY-FELT could be consistently printed into scaffolds for drug delivery. Further, the materials could sustainably release Tetracycline over 3 days, independent of material type and infill geometry. The drug-loaded materials did not show any cytotoxicity when cultured with primary human fibroblasts. We conclude that both LAY-FOMM and LAY-FELT 3D-printed scaffolds are suitable devices for local antibiotic delivery applications, and they may have potential applications to prophylactically reduce infections in orthopedic reconstruction surgery. [ABSTRACT FROM AUTHOR]

Featured Application: Autogenous particulate bone collector (chips) for bone repair and implantation. Autogenous bone grafts can be harvested from either intraoral or extraoral sources. Intra-oral sources include healing tooth extraction wounds, a bone from edentulous ridges, bone trephined from within the jaw using trephine drills, bone formed in wounds, and bone from the maxillary tuberosity, ramus, and mandibular symphysis. Extra-oral sources are the iliac crest, which provides cancellous bone marrow, and the tibia and calvaria. Autogenous bone grafting aids in probing depth reduction, gaining clinical attachment, the bone filling of osseous defects, and the regeneration of new bone, cementum, and periodontal ligaments in teeth. An innovative biomedical device is presented in the form of an autogenous bone collector that can fill defects of 96.91 mm3 with bone particulates, and may be used in bioengineered scaffolds. Experimental studies on synthetic bone have demonstrated the feasibility and applicability of the amount of bone obtained. [ABSTRACT FROM AUTHOR]

Large-volume bone defect regeneration is complex and demands time to complete. Several regeneration phases with unique characteristics, including immune responses, follow, overlap, and interdepend on each other and, if successful, lead to the regeneration of the organ bone's form and function. However, during traumatic, infectious, or neoplastic clinical cases, the intrinsic bone regeneration capacity may exceed, and surgical intervention is indicated. Scaffold-guided bone regeneration (SGBR) has recently shown efficacy in preclinical and clinical studies. To investigate different SGBR strategies over periods of up to three years, we have established a well-characterized ovine large segmental tibial bone defect model, for which we have developed and optimized immunohistochemistry (IHC) protocols. We present an overview of the immunohistochemical characterization of different experimental groups, in which all ovine segmental defects were treated with a bone grafting technique combined with an additively manufactured medical-grade polycaprolactone/tricalcium phosphate (mPCL-TCP) scaffold. The qualitative dataset was based on osteoimmunological findings gained from IHC analyses of over 350 sheep surgeries over the past two decades. Our systematic and standardized IHC protocols enabled us to gain further insight into the complex and long-drawn-out bone regeneration processes, which ultimately proved to be a critical element for successful translational research. [ABSTRACT FROM AUTHOR]

Skeletons play an important role in the human body, and can form gaps of varying sizes once damaged. Bone defect healing involves a series of complex physiological processes and requires ideal bone defect implants to accelerate bone defect healing. Traditional grafts are often accompanied by issues such as insufficient donors and disease transmission, while some bone defect implants are made of natural and synthetic polymers, which have characteristics such as good porosity, mechanical properties, high drug loading efficiency, biocompatibility and biodegradability. However, their antibacterial, antioxidant, anti-inflammatory and bone repair promoting abilities are limited. Flavonoids are natural compounds with various biological activities, such as antitumor, anti-inflammatory and analgesic. Their good anti-inflammatory, antibacterial and antioxidant activities make them beneficial for the treatment of bone defects. Several researchers have designed different types of flavonoid-loaded polymer implants for bone defects. These implants have good biocompatibility, and they can effectively promote the expression of angiogenesis factors such as VEGF and CD31, promote angiogenesis, regulate signaling pathways such as Wnt, p38, AKT, Erk and increase the levels of osteogenesis-related factors such as Runx-2, OCN, OPN significantly to accelerate the process of bone defect healing. This article reviews the effectiveness and mechanism of biomaterials loaded with flavonoids in the treatment of bone defects. Flavonoid-loaded biomaterials can effectively promote bone defect repair, but we still need to improve the overall performance of flavonoid-loaded bone repair biomaterials to improve the bioavailability of flavonoids and provide more possibilities for bone defect repair. [ABSTRACT FROM AUTHOR]

Some reports in the literature show the advantages of fluoride-containing apatite ceramics over hydroxyapatite (HAP), at least in some aspects. While HAP has been used extensively in the treatment of bone defects, fluoridated apatite has hardly been tested in vivo. In order to verify the biological properties of fluoride-doped apatite and to assess its therapeutic potential, we synthesized fluorapatite (FAP) and applied it as a filling in bone defects of experimental animals (rabbits). The treatment effects were evaluated on extracted bones after 3 and 6 months from implantation using peripheral quantitative computed tomography (pQCT), dual-energy X-ray absorptiometry (DXA), radiography (X-ray) and histological staining. The study proved the integration between FAP and the bone tissue, thus indicating its stimulating effect on new bone formation and mineralization. The results achieved after 3 months of treatment were difficult to interpret unequivocally and suggested the transient delay in FAP integration of bone in comparison with HAP. The reasons for this phenomenon are unclear. Most likely, these differences between FAP and HAP resulted mainly from the different porosities, densities and ionic reactivity of the ceramics, which in our opinion affected their solubility, integration and degree of bone tissue resorption. However, it was shown that 6 months after implantation, similar level of bone defect regeneration was achieved for both FAP and HAP. In this article, we present our hypothesis concerning the basis of this phenomenon. [ABSTRACT FROM AUTHOR]

The complex or compromised bone defects caused by osteomyelitis, malignant tumors, metastatic tumors, skeletal abnormalities, and systemic diseases are difficult to be self-repaired, leading to a non-union fracture. With the increasing demands of bone transplantation, more and more attention has been paid to artificial bone substitutes. As biopolymer-based aerogel materials, nanocellulose aerogels have been widely utilized in bone tissue engineering. More importantly, nanocellulose aerogels not only mimic the structure of the extracellular matrix but could also deliver drugs and bioactive molecules to promote tissue healing and growth. Here, we reviewed the most recent literature about nanocellulose-based aerogels, summarized the preparation, modification, composite fabrication, and applications of nanocellulose-based aerogels in bone tissue engineering, as well as giving special focus to the current limitations and future opportunities of nanocellulose aerogels for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Bone grafting is commonly used as a treatment to repair bone defects. However, its use is challenged by the presence of medical conditions that weaken the bone, like osteoporosis. Calcium phosphate cement (CPC) is used to restore bone defects, and it is commonly available as a bioabsorbable cement paste. However, its use in clinical settings is limited by inadequate mechanical strength, inferior anti-washout characteristics, and poor osteogenic activity. There have been attempts to overcome these shortcomings by adding various natural or synthetic materials as enhancers to CPC. This review summarises the current evidence on the physical, mechanical, and biological properties of CPC after doping with synthetic materials. The incorporation of CPC with polymers, biomimetic materials, chemical elements/compounds, and combination with two or more synthetic materials showed improvement in biocompatibility, bioactivity, anti-washout properties, and mechanical strength. However, the mechanical property of CPC doped with trimethyl chitosan or strontium was decreased. In conclusion, doping of synthetic materials enhances the osteogenic features of pure CPC. The positive findings from in vitro and in vivo studies await further validation on the efficacy of these reinforced CPC composites in clinical settings. [ABSTRACT FROM AUTHOR]

Reconstruction of bone defects and maintaining the continuity of the mandible is still a challenge in the maxillofacial surgery. Nowadays, the biomedical research within bone defect treatment is focussed on the therapy of using innovative biomaterials with specific characteristics consisting of the body's own substances. Hydroxyapatite ceramic scaffolds have fully acceptable phase compositions, microstructures and compressive strengths for their use in regenerative medicine. The innovative hydroxyapatite ceramics used by us were prepared using the tape-casting method, which allows variation in the shape of samples after packing hydroxyapatite paste to 3D-printed plastic form. The purpose of our qualitative study was to evaluate the regenerative potential of the innovative ceramic biomaterial prepared using this method in the therapy of the cortical bone of the lower jaw in four mature pigs. The mandible bone defects were evaluated after different periods of time (after 3, 4, 5 and 6 months) and compared with the control sample (healthy cortical bone from the opposite side of the mandible). The results of the morphological, clinical and radiological investigation and hardness examination confirmed the positive regenerative potential of ceramic implants after treatment of the mandible bone defects in the porcine mandible model. [ABSTRACT FROM AUTHOR]

There are many cysts and tumors which might occur in the mandibular and maxillary bones. Their origin can be either odontogenic or non-odontogenic. One of the most common odontogenic cysts is the odontogenic keratocyst (OKC). Its nomenclature and classification have changed many times over years, from a tumor to, finally, a cyst. Nowadays, its treatment has not greatly changed, however, it is related to a potential recurrence rate more than any other cyst of odontogenic origins. OKC size, localization, and possible cortical expansion towards adjacent soft tissues might influence the scope of treatment and possible reoccurrence in time. Each case is quite individual, and after removal of the pathology in some cases there can be a necessity for either bone grafting or any other reconstruction method to restore proper bone continuity. The size and the placement of OKC might influence pathological fracture occurrence or inappropriate healing if the bone cavity after cyst removal is not properly treated. A good healing potential can be achieved with xenograft bone substitutes or allograft fresh–frozen bones. On rare occasions, a titanium plate is used to ensure mandibular stability. In the following case report, an atypical case of a large OKC treated with fresh–frozen bone grafts, supported with collagen barrier material in the anterior mandible with buccal cortical expansion, will be presented. [ABSTRACT FROM AUTHOR]

Background: Various techniques have been reported to treat large, segmental tibial defects, such as autogenous bone graft, vascularized free fibula transfer and bone transport. We present a case of a 24-year-old male with a 17-year history of chronic osteomyelitis with obvious lower limb length discrepancy and severe varus deformity of the tibia secondary to osteomyelitis in childhood. Aim: The aim of this work is to provide an alternative choice for treating patients in developing countries with severe lower limb deformity caused by chronic osteomyelitis. Case Presentations: Without surgical intervention for a prolonged period of time, the patient was admitted in our institute for corrective surgery. Corrective surgery consisted of three stages: lengthening with Ilizarov frame, removal of Ilizarov frame and fixation with externalized locking plate, and removal of externalized locking plate. Tibia bridging was achieved at the distal and proximal junction. The range of motion (ROM) of the knee joint was nearly normal, but the stiffness of the ankle joint was noticeable. The remaining leg discrepancy of 0.1 cm required no application of a shoe lift. Moreover, the patient could engage in daily activities without noted limping. Conclusions: Distraction–compression osteogenesis using the Ilizarov apparatus is a powerful tool to lengthen the shortened long bone and adjust the deformity of the lower limbs. Externalized locking plates provide an alternative to the traditional bulky external fixator, as its low profile makes it more acceptable to patients without compromising axial and torsional stiffness. In all, a combination of Ilizarov frame, externalized locking plate and tibia bridging is an alternative for patients in similar conditions. [ABSTRACT FROM AUTHOR]

Though surgical techniques profoundly influence in vivo experiments, significant heterogeneity exists in current surgeries for inducing rat femoral bone defects. Such variations reduce the reproducibility and comparability of preclinical studies, and are detrimental to clinical translation. The purposes of this study were: (1) to conduct a systematic review of rat femoral defect models, summarizing and analyzing the surgical techniques; (2) to analyze surgical design and potential pitfalls via 3D anatomy and virtual surgeries for fostering future precision research; and (3) to establish a surgical classification system, for improving the reproducibility and comparability among studies, avoiding unnecessary repetitive experiments. The online database PubMed was searched to identify studies from January 2000 to June 2022 using keywords, including rat, femur, bone defect. Eligible publications were included for a review of surgical methods. Anatomical analysis and virtual surgeries were conducted based on micro-CT reconstruction of the rat femur for further investigation and establishment of a classification system. A total of 545 publications were included, revealing marked heterogeneity in surgical methods. Four major surgical designs were reported for inducing defects from the proximal to distal femur: bone tunnel, cortical window, segmental defect, and wedge-shaped defect. Anatomical analysis revealed potential pitfalls hindering efficient clinical translation. A classification system was established according to the anatomical region, surgical design, and fixation devices. This systematic review in combination with 3D analysis and virtual surgery provides a general overview of current surgical approaches to inducing femoral defects in rats, and establishes a surgical classification facilitating preclinical research of quality and translational value. [ABSTRACT FROM AUTHOR]

This scoping review aimed at reporting the outcomes of the bone lid technique in oral surgery in terms of bone healing, ridge preservation, and incidence of complications. Bone-cutting instruments and stabilization methods were also considered. PubMed, Scopus, and the Cochrane Register of Controlled Trials were searched using a combination of terms, including bone lid, bony window, piezosurgery, microsaw, cysts, endodontic surgery, impacted teeth, and maxillary sinus. A hand search was also performed. The last search was conducted on 30 November 2021. No date limitation was set. Searches were restricted to human clinical studies published in English. All types of study design were considered except reviews and case reports. After a two-step evaluation, 20 (2 randomized studies, 2 case-control studies, 3 cohort studies, 13 case series) out of 647 screened studies were included, reporting on 752 bone lid procedures. The bone lid technique was associated with favorable bone healing when compared to other methods, and with a very low incidence of major complications. Clinical indications, surgical procedures, study design, follow-up duration, and outcomes varied among the studies. Overall, favorable outcomes were reported using the bone lid approach, though evidence-based studies were scarce. [ABSTRACT FROM AUTHOR]

Extracorporeal shock wave therapy (ESWT) has been studied and applied extensively in medical practice for various applications including musculoskeletal, dermal, vascular, and cardiac indications. These indications have emerged from primary ESWT use in treating urolithiasis and cholelithiasis. Likewise, dental medicine has had its share of utilizing ESWT in various investigations. This review aimed to provide an up-to-date summary of ESWT use in preclinical and clinical dental medicine. There is growing interest in ESWT use stemming from its non-invasiveness, low cost, and safe qualities in addition to its proven regenerative biostimulating aspects. Targeted tissue and parameters of ESWT delivery continue to be an integral part of successful ESWT treatment to attain the clinical value of the anticipated dose's effect. [ABSTRACT FROM AUTHOR]

The management of severe acetabular bone defects in revision reconstructive orthopedic surgery is challenging. In this study, cyclic precalcification (CP) treatment was used on both nanotube-surface Ti-mesh and a bone graft substitute for the acetabular defect model, and its effects were assessed in vitro and in vivo. Nanotube-Ti mesh coated with hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) was manufactured by an anodizing and a sintering method, respectively. An 8 mm diameter defect was created on each acetabulum of eight rabbits, then treated by grafting materials and covered by Ti meshes. At four and eight weeks, postoperatively, biopsies were performed for histomorphometric analyses. The newly-formed bone layers under cyclic precalcified anodized Ti (CP-AT) meshes were superior with regard to the mineralized area at both four and eight weeks, as compared with that under untreated Ti meshes. Active bone regeneration at 2-4 weeks was stronger than at 6-8 weeks, particularly with treated biphasic ceramic (p < 0.05). CP improved the bioactivity of Ti meshes and biphasic grafting materials. Moreover, the precalcified nanotubular Ti meshes could enhance early contact bone formation on the mesh and, therefore, may reduce the collapse of Ti meshes into the defect, increasing the sufficiency of acetabular reconstruction. Finally, cyclic precalcification did not affect bone regeneration by biphasic grafting materials in vivo. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate, in vitro and in vivo, the suitability of chitosan (CHS) scaffolds produced by the net-shape-nonwoven (NSN) technology, for use as bone graft substitutes in a critical-size femoral bone defect in rats. For in vitro investigations, scaffolds made of CHS, mineralized collagen (MCM), or human cancellous bone allograft (CBA) were seeded with human telomerase-immortalized mesenchymal stromal cells (hTERT-MSC), incubated for 14 days, and thereafter evaluated for proliferation and osteogenic differentiation. In vivo, CHS, MCM and CBA scaffolds were implanted into 5 mm critical-size femoral bone defects in rats. After 12 weeks, the volume of newly formed bone was determined by microcomputed tomography (µCT), while the degree of defect healing, as well as vascularization and the number of osteoblasts and osteoclasts, was evaluated histologically. In vitro, CHS scaffolds showed significantly higher osteogenic properties, whereas treatment with CHS, in vivo, led to a lower grade of bone-healing compared to CBA and MCM. While chitosan offers a completely new field of scaffold production by fibers, these scaffolds will have to be improved in the future, regarding mechanical stability and osteoconductivity. [ABSTRACT FROM AUTHOR]

Bone defects of orthopedic trauma remain a challenge in clinical practice. Regarding bone void fillers, besides the well-known osteoconductivity of most bone substitutes, osteoinductivity has also been gaining attention in recent years. It is known that stromal cell-derived factor-1 (SDF-1) can recruit mesenchymal stem cells (MSCs) in certain circumstances, which may also play an important role in bone regeneration. In this study, we fabricated a gelatin/hyaluronate (Gel/HA) copolymer mixed with hydroxyapatite (HAP) and SDF-1 to try and enhance bone regeneration in a bone defect model. After material characterization, these Gel/HA–HAP and Gel/HA–HAP–SDF-1 composites were tested for their biocompatibility and ability to recruit MSCs in vitro. A femoral condyle bone defect model of rats was used for in vivo studies. For the assessment of bone healing, micro-CT analysis, second harmonic generation (SHG) imaging, and histology studies were performed. As a result, the Gel/HA–HAP composites showed no systemic toxicity to rats. Gel/HA–HAP composite groups both showed better bone generation compared with the control group in an animal study, and the composite with the SDF-1 group even showed a trend of faster bone growth compared with the composite without SDF-1 group. In conclusion, in the management of traumatic bone defects, Gel/HA–HAP–SDF-1 composites can be a feasible material for use as bone void fillers. [ABSTRACT FROM AUTHOR]

Platelet-rich fibrin (PRF) is a natural fibrin meshwork material with multiple functions that are suitable for tissue engineering applications. PRF provides a suitable scaffold for critical-size bone defect treatment due to its platelet cytokines and rich growth factors. However, the structure of PRF not only promotes cell attachment but also, due to its density, provides a pool for cell migration into the PRF to facilitate regeneration. In our study, we used repeated freeze drying to enlarge the pores of PRF to engineer large-pore PRF (LPPRF), a type of PRF that has expanded pores for cell migration. Moreover, a biodegradable Mg ring was used to provide stability to bone defects and the release of Mg ions during degradation may enhance osteoconduction and osteoinduction. Our results revealed that cell migration was more extensive when LPPRF was used rather than when PRF was used and that LPPRF retained the growth factors present in PRF. Moreover, the Mg ions released from the Mg ring during degradation significantly enhanced the calcium deposition of MC3T3-E1 preosteoblasts. In the present study, a bone substitute comprising LPPRF combined with a Mg ring was demonstrated to have much potential for critical-size bone defect repair. [ABSTRACT FROM AUTHOR]

In clinical practice, bone defects still remain a challenge. In recent years, apart from the osteoconductivity that most bone void fillers already provide, osteoinductivity has also been emphasized to promote bone healing. Stromal-cell-derived factor-1 (SDF-1) has been shown to have the ability to recruit mesenchymal stem cells (MSCs), which play an important role in the bone regeneration process. In this study, we developed a gelatin–hyaluronate (Gel-HA) copolymer mixed with calcium sulfate (CS), hydroxyapatite (HAP), and SDF-1 in order to enhance bone regeneration in a bone defect model. The composites were tested in vitro for biocompatibility and their ability to recruit MSCs after material characterization. For the in vivo test, a rat femoral condyle bone defect model was used. Micro computed tomography (Micro-CT), two-photon excitation microscopy, and histology analysis were performed to assess bone regeneration. As expected, enhanced bone regeneration was well observed in the group filled with Gel-HA/CS/HAP/SDF-1 composites compared with the control group in our animal model. Furthermore, detailed blood analysis of rats showed no obvious systemic toxicity or side effects after material implantation. In conclusion, the Gel-HA/CS/HAP/SDF-1 composite may be a safe and applicable material to enhance bone regeneration in bone defects. [ABSTRACT FROM AUTHOR]