Bone Induction Research Articles

Bone‐Induced Nanocomposite Coating with a “Sandwich” Structure

AbstractInfection‐induced bone defects present significant challenges in clinical bone regeneration, frequently leading to poor bone induction, recurring infections, and complications such as pain and chronic inflammation. This study introduces a novel Ti/Lignin‐Ag@PLL composite coating with a “sandwich” structure, designed to integrate pro‐adhesion, photothermal‐photodynamic antibacterial, and osteogenic properties. The Ti/Lignin‐Ag@PLL composite coating is fabricated using self‐assembly technology, in which Ag+ is reduced to silver nanoparticles (Ag‐NPs) by lignin, followed by Polylysine (PLL) grafting. Photothermal conversion efficiency is evaluated under near‐infrared (NIR) laser irradiation, while antibacterial activity is tested against E. coli and S. aureus. Biocompatibility is also assessed using vascular endothelial cells (VECs) and osteoblasts (OBs). The results indicate that the Ti/Lignin‐Ag@PLL coating demonstrates a 31% photothermal conversion efficiency and nearly 100% antibacterial efficacy against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) under NIR irradiation for 10 min. Without irradiation, the antibacterial rates are 85% and 94%, respectively, after 24 h. Additionally, the coating significantly promotes cell adhesion, proliferation, and osteogenesis, as evidenced by the upregulation of Runx2 and Collagen I. This study uniquely contributes to the development of a multifunctional composite coating that effectively combines robust antibacterial properties with enhanced osteogenic potential, offering a promising solution for bone tissue repair and infection prevention.

Incorporating Microbial Stimuli for Osteogenesis in a Rabbit Posterolateral Spinal Fusion Model.

Autologous bone grafts are commonly used to repair defects in skeletal tissue, however, due to their limited supply there is a clinical need for alternatives. Synthetic ceramics present a promising option but currently lack biological activity to stimulate bone regeneration. One potential approach to address this limitation is the incorporation of immunomodulatory agents. In this study, we investigate the application of microbial stimuli to stimulate bone formation. Three different microbial stimuli were incorporated in a biphasic calcium phosphate (BCP) ceramic: Bacille Calmette-Guérin (BCG), gamma-irradiated Staphylococcus aureus (γi-S. aureus), or Candida albicans (γi-C. Albicans). The constructs were then implanted in both a rabbit posterolateral spinal fusion (PLF) and an intramuscular implant model for 10 weeks and compared to a non-stimulated control construct. For the PLF model, the formation of a bony bridge was evaluated by manual palpation, micro-CT, and histology. While complete fusion was not observed, the BCG condition was most promising with higher manual stiffness and almost twice as much bone volume in the central fusion mass compared to the control (9±4.4% bone area vs 4.6±2.3%, respectively). Conversely, the γi-S. aureus or γi-C. albicans appeared to inhibit bone formation (1.4±1.4% and 1.2±0.6% bone area). Bone induction was not observed in any of the intramuscular implants. This study indicates that incorporating immunomodulatory agents in ceramic bone substitutes can affect bone formation, which can be positive when selected carefully. The readily available and clinically approved BCG showed promising results, which warrants further research for clinical translation.

Biosafety and osteogenic properties of a new type of absorbable magnesium-based amorphous alloy

The treatment of bone defects has always been a difficult problem in orthopedic clinical practice, and research on new materials is currently a hot topic. In this study, the biological safety and bone induction ability of a new magnesium-based amorphous alloy (Mg66Zn30Ca3Sr1) and zinc–magnesium powder were verified and compared in animal experiments. Thirty Sprague–Dawley rats were randomly divided into three groups, and a bone defect was made in the lateral condyle of the femur of the left hind limb. The blank group closed the wound after establishing the bone defect model, the control group added zinc–magnesium powder and chondroitin sulfate gel, and the experimental group added magnesium–zinc–calcium–strontium alloy and chondroitin sulfate gel with the same volume. Peripheral venous blood of rats was collected at 4, 8, and 12 weeks postoperatively, and alanine aminotransferase (ALT), aspartate transferase, creatinine, blood urea nitrogen, magnesium ion, and zinc ion levels were evaluated. The expression levels of bone morphogenetic protein 2 (BMP-2), osteoprotegerin (OPG), osteopontin (OPN), core binding factor α1 (RUNX2), and alkaline phosphatase (ALP) were detected using enzyme-linked immunosorbent assay (ELISA). After the rats were euthanized, samples were taken. X-rays and micro-computed tomography (CT) images of the bone defect were obtained, and hematoxylin and eosin and Masson staining were performed. This study shows that amorphous magnesium–zinc–calcium–strontium alloy is a biodegradable metal with good biocompatibility and bone induction and has good application prospects in treating bone defects.

Long-Term Outcomes and a Radiological Assessment of Hydroxyapatite-Tricalcium Phosphate-Coated Total Hip Arthroplasty (Trilogy/Zimmer): A Long-Term Follow-Up Study.

Background and Objectives: Favorable short- and mid-term results for hydroxyapatite (HA)-tricalcium phosphate (TCP)-coated total hip arthroplasty (THA) (Trilogy/Zimmer) have been reported in the literature; however, the long-term results beyond 15 years have not been documented. Therefore, this study evaluated the long-term postoperative results, radiological bone changes, and implant fixation of the acetabular component of HA-TCP-coated THA. Materials and Methods: This is a retrospective cohort study of 212 patients who underwent primary HA-TCP-coated THA (Trilogy/Zimmer) at our institution between 1 October 2002, and 31 March 2008; 166 who were available for follow-up at least 15 years postoperatively were included (capture rate: 78.3%). All implants were Trilogy/Zimmer. We investigated the survival rate, with aseptic loosening as the endpoint. Clinical evaluations included the presence of dislocation and a modified Harris Hip Score (mHHS) preoperatively and at the final observation. Results: The mean age at surgery and at the follow-up period were 57.7 ± 9.6 and 17.1 ± 1.5 years, respectively. The survival rate was 99.4% (165/166), with aseptic loosening as the endpoint. Dislocation was observed in 4/166 (2.4%) patients. The mHHS improved significantly from 46.1 points preoperatively to 82.2 points during the last survey (p < 0.05). The results revealed that fixation was favorable in all cases except for one case of aseptic loosening. The Trilogy implant coated with HA-TCP was highly effective in bone induction, and bone ingrowth was considered to have occurred without failure, further indicating its usefulness. The long-term results of cementless THA using an HA-TCP coating (Trilogy/Zimmer), with a mean follow-up period of 17.1 years, revealed a commendable survival rate of 99.4%, considering aseptic loosening as the endpoint. Conclusions: HA-TCP-coated THA (Trilogy/Zimmer) had good long-term results. However, further long-term observation is required in patients who have undergone this surgery, and the stem side should be evaluated and investigated, including comorbidities.

Molecular Regulation of Bone Turnover in Juvenile Idiopathic Arthritis: Animal Models, Cellular Features and TNFα.

We review the abnormal bone turnover that is the basis of idiopathic inflammatory or rheumatoid arthritis and bone loss, with emphasis on Tumor Necrosis Factor-alpha (TNFα)-related mechanisms. We review selected data on idiopathic arthritis in juvenile human disease, and discuss mouse models focusing on induction of bone resorbing cells by TNFα and Receptor Activator of Nuclear Factor kappa B Ligand (RANKL). In both humans and animal models, macrophage-derived cells in the joint, particularly in the synovium and periosteum, degrade bone and cartilage. Mouse models of rheumatoid arthritis share with human disease bone resorbing cells and strong relation to TNFα expression. In humans, differences in therapy and prognosis of arthritis vary with age, and results from early intervention for inflammatory cytokines in juvenile patients are particularly interesting. Mechanisms that contribute to inflammatory arthritis reflect, in large part, inflammatory cytokines that play minor roles in normal bone turnover. Changes in inflammatory cytokines, particularly TNFα, are many times larger, and presented in different locations, than cytokines that regulate normal bone turnover. Recent data from in vitro and mouse models include novel mechanisms described in differentiation of bone resorbing cells in inflammatory arthritis dependent on the Transient Receptor Potential Channel (TRPC) family of calcium channels. Low-molecular weight (MW) inhibitors of TRPC channels add to their potential importance. Associations with inflammatory arthritis unrelated to TNFα are briefly summarized as pointing to alternative mechanisms. We suggest that early detection and monoclonal antibodies targeting cytokines mediating disease progression deserves emphasis.

Mandibular revascularization using a humeral periosteal free flap: A technical note

The vascularized periosteal free flap transposes a non-irradiated soft tissue with neoangiogenesis, bone induction, and osteogenesis qualities. A surgical technique using a humeral periosteal free flap is described for the treatment of recurrent osteoradionecrosis of the lower jaw. The humeral periosteal free flap is a technique associated with low morbidity. The procedure described avoids sacrificing major vessels as seen in other common flap procedures. Hence, this revascularization approach is equivalent to a prevention technique that should be considered early in the development of osteoradionecrosis to avoid further damage and challenging reconstruction.

Study on the Antibacterial Activity and Bone Inductivity of Nanosilver/PLGA-Coated TI-CU Implants.

Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals. To study the antibacterial activity and bone induction ability of titanium-copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration. We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive Staphylococcus aureus (Sa) and gram-negative Escherichia coli (E. coli) bacteria. Sa was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining. Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects. NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.

A Horn Peptide-Thermoresponsive Hydrogel for Angiogenesis and Bone Regeneration.

The management of critical-sized bone defects presents a formidable clinical challenge, especially given the increasing incidence of bone diseases in the aging population. Consequently, there is an increased demand for minimally invasive bone repair materials that can effectively address this challenge, particularly in outpatient settings. In this study, the goal is to develop an injectable and biodegradable biomaterial that adheres to and fills bone-defect sites to support bone regeneration. The osteogenic and angiogenic activities of animal horn peptides are investigated by incorporating them into biologically active moieties, in combination with a novel thermosensitive hydrogel. The resulting thermosensitive hydrogel exhibited essential biological functionalities, allowing precise modulation of its physical and chemical properties. Notably, the hydrogel incorporating the horn peptide rapidly filled the bone defect site, promoting both angiogenesis and bone induction. Consequently, this approach significantly accelerates new bone regeneration. In summary, the findings of this study present a promising, minimally invasive solution for addressing critical-sized bone defects.

Performance of 3D printed porous polyetheretherketone composite scaffolds combined with nano-hydroxyapatite/carbon fiber in bone tissue engineering: a biological evaluation

Polyetheretherketone (PEEK) has been one of the most promising materials in bone tissue engineering in recent years, with characteristics such as biosafety, corrosion resistance, and wear resistance. However, the weak bioactivity of PEEK leads to its poor integration with bone tissues, restricting its application in biomedical fields. This research effectively fabricated composite porous scaffolds using a combination of PEEK, nano-hydroxyapatite (nHA), and carbon fiber (CF) by the process of fused deposition molding (FDM). The experimental study aimed to assess the impact of varying concentrations of nHA and CF on the biological performance of scaffolds. The incorporation of 10% CF has been shown to enhance the overall mechanical characteristics of composite PEEK scaffolds, including increased tensile strength and improved mechanical strength. Additionally, the addition of 20% nHA resulted in a significant increase in the surface roughness of the scaffolds. The high hydrophilicity of the PEEK composite scaffolds facilitated the in vitro inoculation of MC3T3-E1 cells. The findings of the study demonstrated that the inclusion of 20% nHA and 10% CF in the scaffolds resulted in improved cell attachment and proliferation compared to other scaffolds. This suggests that the incorporation of 20% nHA and 10% CF positively influenced the properties of the scaffolds, potentially facilitating bone regeneration. In vitro biocompatibility experiments showed that PEEK composite scaffolds have good biosafety. The investigation on osteoblast differentiation revealed that the intensity of calcium nodule staining intensified, along with an increase in the expression of osteoblast transcription factors and alkaline phosphatase activities. These findings suggest that scaffolds containing 20% nHA and 10% CF have favorable properties for bone induction. Hence, the integration of porous PEEK composite scaffolds with nHA and CF presents a promising avenue for the restoration of bone defects using materials in the field of bone tissue engineering.

A chitosan-coated PCL/nano-hydroxyapatite aerogel integrated with a nanofiber membrane for providing antibacterial activity and guiding bone regeneration.

A guided bone regeneration (GBR) membrane can act as a barrier to prevent the invasion and interference from foreign soft tissues, promoting infiltration and proliferation of osteoblasts in the bone defect area. Herein, a composite scaffold with dual functions of osteogenesis and antibacterial effects was prepared for GBR. A polycaprolactone (PCL)/nano-hydroxyapatite (n-HA) aerogel produced by electrospinning and freeze-drying techniques was fabricated as the loose layer of the scaffold, while a PCL nanofiber membrane was used as the dense layer. Chitosan (CS) solution served as a middle layer to provide mechanical support and antibacterial effects between the two layers. Morphological results showed that the loose layer had a porous structure with n-HA successfully dispersed in the aerogels, while the dense layer possessed a sufficiently dense structure. In vitro antibacterial experiments illustrated that the CS solution in the middle layer stabilized the scaffold structure and endowed the scaffold with good antibacterial properties. The cytocompatibility results indicated that both fibroblasts and osteoblasts exhibited superior cell activity on the dense and loose layers, respectively. In particular, the dense layer made of nanofibers could work as a barrier layer to inhibit the infiltration of fibroblasts into the loose layer. In vitro osteogenesis analysis suggested that the PCL/n-HA aerogel could enhance the bone induction ability of bone mesenchymal stem cells, which was confirmed by the increased expression of the alkaline phosphatase activity. The loose structure facilitated the infiltration and migration of bone mesenchymal stem cells for better osteogenesis. In summary, such a composite scaffold exhibited excellent osteogenic and antibacterial properties as well as the barrier effect, thus holding promising potential for use as GBR materials.

EFFECTS OF RECOMBINED HUMAN BONE MORPHOGENETIC PROTEIN-2 AS ALVEOLAR RIDGE PRESERVATION ON PAIN REDUCTION AND SOFT TISSUE HEALING PROCESS: A SPLIT MOUTH DESIGNED PILOT STUDY

Background: The alveolar ridge undergoes physiological bone resorption following tooth extraction. Several alveolar ridge preservation (ARP) techniques have been researched and developed in an effort to reduce this process and maintain a favorable volume and morphology of the alveolar ridge for appropriate implant placement. Bone morphogenetic proteins (BMPs) are proteins derived from a subgroup of the transforming growth factor  family that accelerates ossification by controlling essential factors of the bone induction cascade, resulting in the proliferation of osteoblasts from mesenchymal stem cells and the biosynthesis of bone matrices. One of these BMPs is recombinant human bone morphogenetic protein-2 (rhBMP-2) that has been authorized to be used for ARP. Objective: This study aims to evaluate the effect of rhBMP-2 on the healing process and the level of pain following dental extraction. Methods: In this split-mouth pilot study, 11 patients underwent extractions of a minimum of two teeth, and randomly, one of the alveolar sockets was filled with a hemostatic sponge while the other was filled with a hemostatic sponge embedded with rhBMP-2. Both sockets were sutured using the X technique. Wound healing measurements were done on days 3, 7, and 14, and each participant was requested to document his pain experience using the Numerical Rating Scale (NRS). Results: In accordance with clinical evidence, it was observed that the mean pain score was at its peak on day 0 and progressively diminished in the subsequent days. Notably, this decline was more pronounced in the rhBMP-2 group compared to the control group. Importantly, a statistically significant reduction in pain level was detected on day 3 within the rhBMP-2 group, in contrast to the control group (P-value &lt; 0.05). This indicated that the application of rhBMP-2 led to a noteworthy and meaningful alleviation of pain on the third day after treatment, surpassing the impact observed in the control group. For the wound healing changes, it uncovered statistically significant mean differences across various time intervals: day 0 and day 3, day 0 and day 7, day 0 and day 14, day 3 and day 7, and day 7 and day 14 (P-value &lt; 0.0001). These significant differences strongly suggest dynamic changes in wound closure rates over time. Furthermore, the observed differences were more pronounced in the rhBMP-2-treated group compared to the control group. This augmentation of differences indicates that the utilization of rhBMP-2 for ARP within a fresh socket site resulted in a heightened acceleration of the wound healing process. Conclusion: Our results suggest that rhBMP-2 can decrease post-operative pain after tooth extraction and accelerate the soft tissue healing process.

Bone regeneration in critical-size defects of the mandible using biomechanically adapted CAD/CAM hybrid scaffolds: An in vivo study in miniature pigs

The study aimed to analyze bone regeneration in critical-size defects using hybrid scaffolds biomechanically adapted to the specific defect and adding the growth factor rhBMP-2.For this animal study, ten minipigs underwent bilateral defects in the corpus mandibulae and were subsequently treated with novel cylindrical hybrid scaffolds. These scaffolds were designed digitally to suit the biomechanical requirements of the mandibular defect, utilizing finite element analysis. The scaffolds comprised zirconium dioxide-tricalcium phosphate (ZrO2-TCP) support struts and TCP foam ceramics. One scaffold in each animal was loaded with rhBMP-2 (100 μg/cm³), while the other served as an unloaded negative control. Fluorescent dyes were administered every 2 weeks, and computed tomography (CT) scans were conducted every 4 weeks. Euthanasia was performed after 3 months, and samples were collected for examination using micro-CT and histological evaluation of both hard and soft tissue.Intravital CT examinations revealed minor changes in radiographic density from 4 to 12 weeks postoperatively. In the group treated with rhBMP-2, radiographic density shifted from 2513 ± 128 (mean ± SD) to 2606 ± 115 Hounsfield units (HU), while the group without rhBMP-2 showed a change from 2430 ± 131 to 2601 ± 67 HU. Prior to implantation, the radiological density of samples measured 1508 ± 30 mg HA/cm³, whereas post-mortem densities were 1346 ± 71 mg HA/cm³ in the rhBMP-2 group and 1282 ± 91 mg HA/cm³ in the control group (p = 0.045), as indicated by micro-CT measurements. The histological assessment demonstrated successful ossification in all specimens. The newly formed bone area proportion was significantly greater in the rhBMP-2 group (48 ± 10%) compared with the control group without rhBMP-2 (42 ± 9%, p = 0.03). The mean area proportion of remaining TCP foam was 23 ± 8% with rhBMP-2 and 24 ± 10% without rhBMP-2.Successful bone regeneration was accomplished by implanting hybrid scaffolds into critical-size mandibular defects. Loading these scaffolds with rhBMP-2 led to enhanced bone regeneration and a uniform distribution of new bone formation within the hybrid scaffolds. Further studies are required to determine the adaptability of hybrid scaffolds for larger and potentially segmental defects in the maxillofacial region.

Metal Ion-Doped Hydroxyapatite-Based Materials for Bone Defect Restoration.

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.

Effects of Dickkopf-1 (DKK-1) on Prostate Cancer Growth and Bone Metastasis.

Osteoblastic bone metastases are commonly detected in patients with advanced prostate cancer (PCa) and are associated with an increased mortality rate. Dickkopf-1 (DKK-1) antagonizes canonical WNT/β-catenin signaling and plays a complex role in bone metastases. We explored the function of cancer cell-specific DKK-1 in PCa growth, metastasis, and cancer-bone interactions using the osteoblastic canine PCa cell line, Probasco. Probasco or Probasco + DKK-1 (cells transduced with human DKK-1) were injected into the tibia or left cardiac ventricle of athymic nude mice. Bone metastases were detected by bioluminescent imaging in vivo and evaluated by micro-computed tomography and histopathology. Cancer cell proliferation, migration, gene/protein expression, and their impact on primary murine osteoblasts and osteoclasts, were evaluated in vitro. DKK-1 increased cancer growth and stimulated cell migration independent of canonical WNT signaling. Enhanced cancer progression by DKK-1 was associated with increased cell proliferation, up-regulation of NF-kB/p65 signaling, inhibition of caspase-dependent apoptosis by down-regulation of non-canonical WNT/JNK signaling, and increased expression of epithelial-to-mesenchymal transition genes. In addition, DKK-1 attenuated the osteoblastic activity of Probasco cells, and bone metastases had decreased cancer-induced intramedullary woven bone formation. Decreased bone formation might be due to the inhibition of osteoblast differentiation and stimulation of osteoclast activity through a decrease in the OPG/RANKL ratio in the bone microenvironment. The present study indicated that the cancer-promoting role of DKK-1 in PCa bone metastases was associated with increased growth of bone metastases, reduced bone induction, and altered signaling through the canonical WNT-independent pathway. DKK-1 could be a promising therapeutic target for PCa.

Prognostic factors, outcomes, and complications for dental autotransplantation: an umbrella review.

Dental autotransplantation (DAT) is a biological way of replacing missing or compromised teeth for patients. The techniques often necessitate a multi-disciplinary approach. The prognosis and success of the procedure may be impacted by variable factors in varying degrees. Evaluating outcomes and complications of DAT, including prognostic factors using an umbrella review. Six databases were searched for all relevant systematic reviews published up to 30 June 2022. No restrictions were applied to language or publication date. Systematic reviews and meta-analyses of DAT studies. Identification, screening, eligibility, and quality assessment using the AMSTAR 2 tool were performed independently by two authors (M.C. and S.A.). Two studies (20%) scored moderate, six studies (60%) scored low, and two studies (20%) scored critically low. Data were analysed using a random effects meta-analysis, and meta-regression was performed to investigate the effect of open and closed apices on the dependent variables. The results were summarised as relative risk ratios. A total of 310 studies were eligible for inclusion, of which 20 studies were selected for full-text evaluation. Ten systematic reviews were included, 9 of which had a meta-analysis. Overall findings suggest that DAT offers favourable success and survival rates. Meta-regression results indicate that a closed apex increased the proportion of ankylosis and resorption, reduced survival but had no effect on success during the observational period. A varying degree of heterogeneity and bias was present in all systematic reviews. The samples of donor teeth included in the systematic reviews also varied morphologically. DAT is a technique-sensitive procedure requiring a multidisciplinary team, vigilant case assessment and thorough consideration of the respective prognostic factors involved. Despite methodological limitations reported across studies, DAT shows favourable success and survival rates, with a distinctive advantage of bone induction and soft tissue thickness preservation, and should, therefore, be considered as a viable treatment modality. Standardisation of clinical guidelines and practice are highly recommended. CRD42020202484.

A dual-functional strontium-decorated titanium implants that guides the immune response for osseointegration of osteoporotic rats

Due to the dynamic imbalance between osteogenesis and osteoclasis and the abnormal inflammatory microenvironment in situ, osteoporosis hampers the early osseointegration between implants and bones. To improve osseointegration with the osteoporosis, we first coated the titanium implants (Ti) with polydopamine (PDA) coating (Ti-PDA), followed by modification with strontium (Sr) to prepare the Ti-PDA-Sr implants. An osteoporotic rat model with femoral bone defect was verified to estimate the osseointegration of the implants. The Ti-PDA-Sr implants exhibited good biocompatibility with continuous release of Sr ions for up to 21 days. Ti-PDA-Sr implants promoted the osteogenesis of BMSCs and the polarization of BMMs to M2 phenotype compared to that of Ti and Ti-PDA implants, revealing the double-regulated effects in bone induction and immune regulation. According to the Micro-CT and histopathology results, Ti-PDA-Sr implants exhibited the most stable osseointegration between bone tissues and implants. According to the immunohistochemistry results, the Ti-PDA-Sr implants differentiated the BMMs to M2 phenotype, alleviating the abnormal inflammation in osteoporosis and preventing the consistent bone destruction between the implants and bone tissues. This study provides a practical and effective strategy in preparing bi-functional implants that can promote osseointegration with osteoporosis.

Nanoclay-Modified Hyaluronic Acid Microspheres for Bone Induction by Sustained rhBMP-2 Delivery.

Microspheres (MSs) are ideal candidates as biological scaffolds loading with growth factors or cells for bone tissue engineering to repair irregular alveolar bone defects by minimally invasive injection. However, the high initial burst release of growth factor and low cell attachment limit the application of microspheres. The modification of microspheres often needs expensive experiments facility or complex chemical reactions, which is difficult to achieve and may bring other problems. In this study, a sol-grade nanoclay, laponite XLS is used to modify the surface of MSs to enhance its affinity to either positively or negatively charged proteins and cells without changing the interior structure of the MSs. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is used as a representation of growth factor to check the osteoinduction ability of laponite XLS-modified MSs. By modification, the protein sustained release, cell loading, and osteoinduction ability of MSs are improved. Modified by 1% laponite XLS, the MSs can not only promote osteogenic differentiation of MC3T3-E1 cells by themselves, but also enhance the effect of the rhBMP-2 below the effective dose. Collectively, the study provides an easy and viable method to modify the biological behavior of microspheres for bone tissue regeneration.

Modified Lightbulb Non-Vascularized Bone Grafting Technique for Osteonecrosis of the Femoral Head.

Multiple techniques for non-vascularized bone grafting for the treatment of femoral head osteonecrosis have been proposed with varying degrees of success. The success of these procedures may be improved with the use of ancillary growth and differentiation factors. The trephine (Phemister) technique allows for limited decompression of the femoral head through two percutaneous tunnels, while the direct approach through the femoral head ("trapdoor" technique) may result in damage to the articular cartilage. Herein we provide our modified "lightbulb" technique to decompress the femoral head through a window at the femoral head-neck junction that provides excellent, direct access to the osteonecrotic lesion. Adjuvant, non-vascularized bone graft, comprised of bone marrow aspiration concentrate (BMAC) and open matrix bone graft (MagnetOs Flex Matrix, Kuros Bioscience, Bilthoven, Netherlands) is a unique fibrillar and flexible structure that provides bone induction and further structural support to create a favorable environment for bone formation and healing. This is a straight-forward, hip-preserving, surgical technique that may be used for symptomatic management to delay, or potentially obviate, the need for total hip arthroplasty in patients who have medium- to large-sized or early-collapse lesions of the femoral head.

A tailored hydroxyapatite/magnesium silicate 3D composite scaffold: Mechanical, degradation, and bioactivity properties

Today, hydroxyapatite (HA)-based composite scaffolds are widely studied, but there is a lack of a doping method that can simultaneously improve the mechanical strength, degradation rate, and bioactivity of HA scaffolds. In this paper, the amorphous magnesium silicate (MS) with a low melting point is selected as the doping phase of HA. The hydroxyapatite/magnesium silicate composite was fabricated using photocuring technology. In addition, at high temperatures, ionic substitution can occur between the magnesium silicate glass phase and the HA lattice. Therefore, a new phase with a pinning effect can be obtained at the grain boundary and the magnesium silicate can further improve the biocompatibility of HA scaffolds. In the sintering process, the magnesium silicate was melted to a liquid state, and then the sintering temperature of the scaffold was reduced for grain refinement. The morphological analysis shows that MS doping is an important factor for grain refinement, which has been reduced from 12 μm to 6 μm. Furthermore, the formation of new diopside and whitlockite phases with a pinning effect has been observed at the grain boundaries. Specifically, the compressive stress of the composite scaffold is increased by 59.15% compared to the pure HA scaffold. However, the soaking and cell experimental findings show that the composite scaffold has a better degradation rate, cell activity, and bone induction. Finally, this study found that a composite scaffold with improved mechanical strength, degradation performance, and biocompatibility can be obtained with the addition of magnesium silicate as the doping phase of HA with 30 wt% of.

Enhanced bone regeneration via local low-dose delivery of PTH1-34 in a composite hydrogel.

Introducing bone regeneration-promoting factors into scaffold materials to improve the bone induction property is crucial in the fields of bone tissue engineering and regenerative medicine. This study aimed to develop a Sr-HA/PTH1-34-loaded composite hydrogel system with high biocompatibility. Teriparatide (PTH1-34) capable of promoting bone regeneration was selected as the bioactive factor. Strontium-substituted hydroxyapatite (Sr-HA) was introduced into the system to absorb PTH1-34 to promote the bioactivity and delay the release cycle. PTH1-34-loaded Sr-HA was then mixed with the precursor solution of the hydrogel to prepare the composite hydrogel as bone-repairing material with good biocompatibility and high mechanical strength. The experiments showed that Sr-HA absorbed PTH1-34 and achieved the slow and effective release of PTH1-34. In vitro biological experiments showed that the Sr-HA/PTH1-34-loaded hydrogel system had high biocompatibility, allowing the good growth of cells on the surface. The measurement of alkaline phosphatase activity and osteogenesis gene expression demonstrated that this composite system could promote the differentiation of MC3T3-E1 cells into osteoblasts. In addition, the in vivo cranial bone defect repair experiment confirmed that this composite hydrogel could promote the regeneration of new bones. In summary, Sr-HA/PTH1-34 composite hydrogel is a highly promising bone repair material.