Bone Regenerative Effect Research Articles

Injectable biodegradable gelatin-methacrylate/β‐tricalcium phosphate composite for the repair of bone defects

Maintaining appropriate mechanical strength and tissue volume is important to provide for sufficient alveolar bone growth. Recently, synthetic bone graft materials (BGM) including hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) have been widely studied for alveolar bone regeneration. Here, we applied gelatin-methacrylate (GelMA) hydrogel into the β-TCP to produce a GelMA/β-TCP composite (GelMA-B). This reinforced the mechanical strength and regulated the absorption period of β-TCP. To characterize the physical properties of the formed composite, GelMA-B was tested using a mechanical tester and a rheometer. It was then analyzed for biocompatibility and osteogenic differentiation using human adipose-derived stem cells. Further, the bone regeneration effects of GelMA-B were confirmed by an animal study. The cell viability analysis and qPCR results revealed that GelMA-B showed high cell viability and relatively high bone differentiation ability. In a rheological analysis, GelMA-B showed higher mechanical strength than β-TCP and GelMA alone. These features were confirmed in the animal study as GelMA-B maintained its volume and shape during regrowth, which can be favorable for alveolar bone regeneration. In addition to the regenerative effect, GelMA-B composite has an advantage for clinical use as the material enables structural molding for customized application.

Combination of polyetherketoneketone scaffold and human mesenchymal stem cells from temporomandibular joint synovial fluid enhances bone regeneration

Therapies using human mesenchymal stem cells (MSCs) combined with three-dimensional (3D) printed scaffolds are a promising strategy for bone grafting. But the harvest of MSCs still remains invasive for patients. Human synovial fluid MSCs (hSF-MSCs), which can be obtained by a minimally invasive needle-aspiration procedure, have been used for cartilage repair. However, little is known of hSF-MSCs in bone regeneration. Polyetherketoneketone (PEKK) is an attractive bone scaffold due to its mechanical properties comparable to bone. In this study, 3D-printed PEKK scaffolds were fabricated using laser sintering technique. hSF-MSCs were characterized and cultured on PEKK to evaluate their cell attachment, proliferation, and osteogenic potential. Rabbit calvarial critical-sized bone defects were created to test the bone regenerative effect of PEKK with hSF-MSCs. In vitro results showed that hSF-MSCs attached, proliferated, and were osteogenic on PEKK. In vivo results indicated that PEKK seeded with hSF-MSCs regenerated twice the amount of newly formed bone when compared to PEKK seeded with osteogenically-induced hSF-MSCs or PEKK scaffolds alone. These results suggested that there was no need to induce hSF-MSCs into osteoblasts prior to their transplantations in vivo. In conclusion, the combined use of PEKK and hSF-MSCs was effective in regenerating critical-sized bone defects.

A study of bone regeneration effect according to the two different graft bone materials in the cranial defects of rabbits

A study of bone regeneration effect according to the two different graft bone materials in the cranial defects of rabbits

Comparative evaluation of the osteogenic capacity of human mesenchymal stem cells from bone marrow and umbilical cord tissue.

Mesenchymal stem cells (MSCs) have been extensively investigated in the field of regenerative medicine. Human bone MSCs (BMSCs) have become a common type of seed cell for bone tissue engineering. However, the viability and cell number of BMSCs are negatively correlated with donor age, and as the extraction process is painful, this method has not been widely used. As human umbilical cord MSCs (UCMSCs) may be harvested inexpensively and inexhaustibly, the present study evaluated and compared the regenerative potential of UCMSCs and BMSCs to determine whether UCMSCs may be used as a novel cell type for bone regeneration. In the present study, the proliferation and osteogenic capacity of BMSCs and UCMSCs was compared in vitro. BMSCs and UCMSCs were respectively combined with biofunctionalized macroporous calcium phosphate cement, and their bone regenerative potentials were determined by investigating their capacity for ectopic bone formation in a nude mouse model as well as their efficacy in a rat model of tibia bone defect. The extent of bone regeneration was examined by X-ray, histological and immunohistochemical analyses. The results revealed that UCMSCs exhibited a good osteogenic differentiation potential, similarly to that of BMSCs, and that UCMSCs were able to contribute to the regeneration of bone and blood vessels. Furthermore, no significant differences were identified between BMSCs and UCMSCs in terms of their bone regenerative effect.

Patient-Specific Titanium-Reinforced Calcium Phosphate Implant for the Repair and Healing of Complex Cranial Defects

The reconstruction of complex cranial defects is challenging and is associated with a high complication rate. The development of a patient-specific, titanium-reinforced, calcium phosphate-based (CaP-Ti) implant with bone regenerative properties has previously been described in 2 case studies with the hypothesis that the implant may improve clinical outcome. To identify whether the introduction of CaP-Ti implant has the potential to improve clinical outcome. A retrospective review of all patients having undergone CaP-Ti cranioplasty was conducted. Comprehensive clinical data were collected from the hospital computer database and patient records. Bone formation and osseointegration were analyzed in a single retrieval specimen. Fifty patients, with 52 cranial defects, met the inclusion criteria. The patient cohort displayed a previous failure rate of 64% (32/50) with autologous bone, alloplastic materials, or both. At a median follow-up time of 25 months, the explantation rate due to either early postoperative infection or persistent wound dehiscence was 1.9% (1/53) or 3.8% (2/53), respectively. Surgical intervention with local wound revision was required in 2 patients without the need of implant removal. One patient had a brain tumor recurrence, and the implant was explanted 31 months after implantation. Histologic examination showed that the entire implant was partly yet evenly transformed into vascularized compact bone. In the present study the CaP-Ti implant appears to have improved the clinical outcomes in a cohort of patients with a high rate of previous cranioplasty failures. The bone regenerative effect may in particular have an impact on the long-term success rate of the implant.

Modulatory effect of simultaneously released magnesium, strontium, and silicon ions on injectable silk hydrogels for bone regeneration

Injectable silk hydrogels are ideal carriers of therapeutic agents due to their biocompatibility and low immunogenicity. Injectable silk hydrogels for bone regeneration have been previously developed but often utilize expensive biologics. In this study, we have developed an injectable silk composite incorporated with a triphasic ceramic called MSM-10 (54 Mg2SiO4, 36 Si3Sr5 and 10 MgO (wt%)) capable of simultaneously releasing magnesium, silicon, and strontium ions into its environment. These ions have been previously reported to possess therapeutic effects for bone regeneration. MSM-10 particles were incorporated into the silk hydrogels at various weight percentages [0.1 (SMH-0.1), 0.6 (SMH-0.6), 1 (SMH-1) and 2 (SMH-2)]. The effects of the released ions on the physicochemical and biological properties of the silk hydrogel were comprehensively evaluated. Increased MSM-10 loading was found to hinder the gelation kinetics of the silk hydrogel through the reduction of beta-sheet phase formation, which in turn affected the required sonication time for gelation, compressive strength, force of injection, microstructure and in vitro degradation rate. Primary human osteoblasts seeded on SMH-0.6 demonstrated increased proliferation and early alkaline phosphatase activity, as well as enhanced osteogenic gene expression compared to pure silk hydrogel and SMH-0.1. In vivo results in subcutaneous mouse models showed both decreased fibrous capsule formation and increased number of new blood vessels around the injected SMH-0.1 and SMH-0.6 implants compared to pure silk hydrogels. The results in this study indicate that the ions released from MSM-10 is able to influence the physicochemical and biological properties of silk hydrogels, and SMH-0.6 in particular shows promising properties for bone regeneration.

Preparation of Calcium Phosphate Glasses Containing Nb<sub>2</sub>O<sub>5</sub> and TiO<sub>2</sub>

60CaO-30P2O5-(10 ̶ x)Nb2O5-xTiO2 (x = 0 ~ 10, mol%) glasses were prepared in order to obtain biomaterials with high chemical durability and therapeutic ions releasability. Dissolution test of these glasses using Tris buffer solution showed the controlled release of niobate ions from Nb2O5-containing glasses and the formation of calcium titanate in some of them. These behavior might induce positive effects for bone regeneration.

The use of hydroxyapatite bone substitute grafting for alveolar ridge preservation, sinus augmentation, and periodontal bone defect: A systematic review

ObjectivesWe determined and structurally analyzed the reported effect of hydroxyapatite (HA) bone substitute on alveolar bone regeneration. To the best of our knowledge, no systematic reviews have previously reported the bone regenerative effect of the HA bone substitute. Materials and methodsA literature search was performed for articles published up to August 2015 using MEDLINE with the search terms “hydroxyapatite,” “bone regeneration,” and “alveolar bone” as well as their known synonyms. The inclusion criteria were set up for human trials with at least five patients. The literature search, eligible article selection, and data extraction were independently performed by two readers, and their agreement was reported by κ value. ResultsOf the 504 studies found using the MEDLINE literature search, 241 were included for further steps (inter-reader agreement, κ = 0.968). Abstract screening yielded 74 studies (κ = 0.910), with 42 completely fulfilling the inclusion criteria (κ = 0.864). In a final step, 42 studies were further analyzed, with 17 and 25 studies with and without statistical analysis, respectively. The 17 studies reporting similar outcome measures were compared using the calculated 95% confidence intervals. The effect of HA on ridge preservation could not be evaluated. ConclusionsThe use of the HA bone substitute interfered with the normal healing process, with significant differences found for sinus augmentation but not for periodontal bone defects. Thus, a bone substitute with optimal bone regenerative properties for alveolar ridge or socket preservation, sinus augmentation, and periodontal bony defect should be developed.

Solidification Analysis of Mg–4Zn–xSr System to Study Phase Transformations in Mg-Rich Corner

Mg–Zn–Sr alloys are suitable for biodegradable orthopaedic implants due to excellent biocompatibility and bone regeneration effect of Sr. For Sr additions exceeding 0.2 wt%, ternary phases are observed in the microstructure contrary to binary MgxZny and Mg17Sr2 intermetallics predicted by the existing phase diagrams and corrosion and mechanical properties reduce drastically. Thermal analysis employed for Mg–4Zn–xSr alloys (0 ≤ x≤2) recorded two peaks, hitherto unreported, at temperatures of ~ 514 and 409 °C with 2 wt%, and ~ 549 and 428 °C with 1 wt% of Sr added to Mg–4Zn alloy. In conjunction with SEM–EDAX and XRD analysis, one of these phases is identified as Mg11Zn4Sr3, with second one an unknown intermetallic (IM2). Formation of Mg17Sr2 phase is suppressed in the presence of Zn, and the ternary phase is favoured beyond the solid solubility of Sr in Mg. Solidification pathway of L → α-Mg + Mg11Zn4Sr3 + unknown intermetallic (IM2) has been proposed for the ternary compositions with Sr > 0.2 wt% investigated in the current study.

Preparation of Calcium Phosphate Coated Simvastatin-Loaded PLGA Microspheres Dispersed Alginate Hydrogel Beads as a Controlled Drug Delivery Carrier

Simvastatin (SIM) is widely used as a cholesterol-lowering drug known to affect bone formation in vivo and its sustainable administration into localized area is of particular interest. We reported previously that sustained SIM release from poly (lactic-co-glycolide) (PLGA) microspheres could maintain relatively low concentration in the bone defect area, resulting in the improved bone regeneration effect. The aim of this study was to determine the release characteristics of SIM from calcium phosphate coated SIM-loaded PLGA Microspheres (CSPMs) dispersed into an alginate hydrogel bead (with different drug release profiles), since we speculated that further sustainable SIM release would be more effective related to stimulate the formulation of BMP-2, resulting in the promoted bone regeneration.

Egyptian propolis compared to nanohydroxyapatite graft in the treatment of Class II furcation defects in dogs.

Complementary and alternative medicine approaches are gaining ground in everyday practice. Propolis is a bee product that has been suggested to have bone regenerative effects. This study was conducted to compare the effectiveness of Egyptian propolis with nanohydroxyapatite graft on furcation defect regeneration in mongrel dogs. A split mouth design was utilized in six clinically healthy mongrel dogs. A total of 24 Class II furcation defects were surgically created in mandibular third and fourth premolars. The defects on the right side were filled with nanohydroxyapatite graft and covered with collagen membrane, while on the left side the defects were filled with propolis and also covered with collagen membrane. The dogs were sacrificed after 1 and 3 months. Segments containing the defects were prepared for histological evaluation. The histological evaluation after one month revealed newly formed bone in both treatment groups. However, after 3 months, the bone trabeculae appeared thinner in the collagen/nanohydroxyapatite group than in the collagen/propolis group. The histomorphometric evaluation showed a significant increase in bone height as well as bone surface area for the collagen/propolis group compared to collagen/nanohydroxyapatite group. Both Egyptian propolis and nanohydroxyapatite graft material showed favorable periodontal regenerative effect. Propolis showed increased cellular proliferative ability that could be beneficial in reducing the healing period needed after periodontal therapy.

Dopamine-functionalized sulphated hyaluronic acid as a titanium implant coating enhances biofilm prevention and promotes osseointegration

A series of new hyaluronan derivatives was synthesized and tested as an antibiotic release system by antibacterial and osseointegration assays. Specifically, partially sulphated hyaluronic acid (sHA) was functionalized with dopamine (DA). The DA moiety guarantees good performance as a binding agent for coating a titanium alloy surface; furthermore, the negatively charged sHA has bone regenerative effects and a high binding affinity for positively charged antibiotics. A sHA scaffold with a defined degree of sulphation (DS =2) was selected as a good compromise between a high negative charge density and poor heparin-like anticoagulant activity, while the degree of DA derivatization (17.1%mol) was chosen based on the absence of cytotoxic activity and the promotion of osteoblast proliferation. The titanium alloy coating was investigated indirectly using a fluorescent probe and directly by environmental scanning electron microscope (ESEM) analysis. Long-duration antibiotic release was demonstrated in vitro, and antibacterial efficacy against a Staphylococcus aureus culture was shown.

Low power laser irradiation and human adipose-derived stem cell treatments promote bone regeneration of critical-sized calvarial defects in rats

The treatments of large bone defects are often accompanied by various limitations and complications. Stem cell therapy and physical treatments have both been shown to be beneficial in accelerating bone healing. However, the efficacy of combined treatment with stem cells and physical stimuli on large bone defects remains uncertain. The aim of this study was to evaluate the bone regeneration effects of low power laser irradiation (LPLI) and human ADSC treatments during fracture repair using a comparative rat calvarial defect model. The viability of human ADSCs was cultured on a porous PLGA scaffold using an MTS assay. The critical-sized (7 mm) calvarial bone defect Sprague–Dawley (SD) rats were divided into 4 groups: a control group, an LPLI group, an ADSC group, and an ADSC + LPLI group. Bone formation was evaluated using micro-CT at 4, 8, 12, and 16 weeks after surgery. New bone formation areas and osteogenic factor expression levels were then examined by histomorphological analysis and immunohistochemical staining. PLGA had no cytotoxic effect on human ADSCs. Micro-CT analyses showed that both the LPLI and ADSC groups improved calvarial bone defect healing compared to the control group. In addition, the ADSC + LPLI group showed significantly increased bone volume at 16 weeks after surgery. The area of new bone formation ranked as follows: control group < LPLI group < ADSC group < ADSC + LPLI group. There were significant differences between the groups. The ADSC and ADSC + LPLI groups showed strong signals of vWF expression in week 16. ADSC and LPLI treatments improve fracture repair in critical-sized calvarial defects in rats. Importantly, the combined treatment of ADSCs and further enhances the bone healing process.

The Bone Regenerative Effects of the Biofield Energy Treated Vitamin D3 in Human Bone Osteosarcoma Cells (MG-63)

The Bone Regenerative Effects of the Biofield Energy Treated Vitamin D3 in Human Bone Osteosarcoma Cells (MG-63)

The Bone Regenerative Effects of the Biofield Energy Treated Vitamin D3 in Human Bone Osteosarcoma Cells (MG-63)

The Bone Regenerative Effects of the Biofield Energy Treated Vitamin D3 in Human Bone Osteosarcoma Cells (MG-63)

The Bone Regenerative Effects of the Biofield Energy Treated Vitamin D3 in Human Bone Osteosarcoma Cells (MG-63)

1. Abstract <span style=font-size:10.0pt; font-family: times= new= roman,serif=>The current research work was presented to evaluate impact of Biofield Energy Treated vitamin D3 and DMEM on bone health in <span style=font-size:10.0pt;font-family: times= new= roman,serif;mso-fareast-language:en-in=>human bone osteosarcoma cells (MG-63). The Test Items (TI), were distributed into two parts. One part of each sample was received Consciousness Energy Healing Treatment by James Jeffery Peoples and labeled as Biofield Energy Treated (BT) samples, while other parts of each sample were denoted as Untreated Test Items (UT). Test samples were found as safe in tested concentrations by MTT assay. ALP was significantly increased by 54.43% and 111.24% at 10 and 100 µg/mL, respectively in BT-DMEM + UT-TI than UT-DMEM + UT-TI. Moreover, ALP was significantly elevated by 128.14%, 77.84%, and 62.28% in UT-DMEM + BT-TI, BT-DMEM + UT-TI, and BT-DMEM + BT-TI, respectively at 1 µg/mL compared to untreated. Collagen was significantly increased by 286.67% and 340% in BT-DMEM + UT-TI and BT-DMEM + BT-TI, respectively at 0.1 µ g/mL, while increased by 134.08% in UT-DMEM + BT-TI at 10 µ g/mL than untreated. Besides, <span style=font-size:10.0pt; font-family: times= new= roman,serif=>percent of bone mineralization was remarkably increased by 140.94%, 113.72%, and 129.87% at 1 µg/mL in <span style=font-size:10.0pt; font-family: times= new= roman,serif;mso-fareast-language:en-in=>UT-DMEM + BT-TI, BT-DMEM + UT-TI, and BT-DMEM + BT-TI, respectively, while increased by 187.91% in BT-DMEM + UT-TI at 0.1 µ <span style=font-size:10.0pt; font-family: times= new= roman,serif=>g/mL <span style=font-size:10.0pt; font-family: times= new= roman,serif;mso-fareast-language:en-in=>than untreated. Altogether, Biofield Treated vitamin D3 was significantly improved the bone growth and it could be able to fight against various bone-related disorders (osteoporosis, osteogenesis imperfecta, Paget’s disease, rickets, osteomalacia), autoimmune and inflammatory diseases, stress management, and anti-aging by improving overall health. 2. Keywords: Biofield Energy Treatment; <span style=font-size:10.0pt; font-family: times= new= roman,serif=>Bone Health; Osteosarcoma cells; <span style=font-size:10.0pt;font-family: times= new= roman,serif=>Osteoporosis; The Trivedi Effect®

Low power laser irradiation and human adipose-derived stem cell treatments promote bone regeneration in critical-sized calvarial defects in rats.

Both stem cell therapy and physical treatments have been shown to be beneficial in accelerating bone healing. However, the efficacy of combined treatment with stem cells and physical stimuli for large bone defects remains uncertain. The aim of this study was to evaluate the bone regeneration effects of low-power laser irradiation (LPLI) and human adipose-derived stem cell (ADSC) treatments during fracture repair using a comparative rat calvarial defect model. We evaluated the viability of human ADSCs, which were cultured on a porous PLGA scaffold using an MTS assay. The critical-sized calvarial bone defect rats were divided into 4 groups: control group, LPLI group, ADSC group, and ADSC+LPLI group. Bone formation was evaluated using micro-CT. New bone formation areas and osteogenic factor expression levels were then examined by histomorphological analysis and immunohistochemical staining. Our data showed that PLGA had no cytotoxic effect on human ADSCs. Micro-CT analyses revealed that both the LPLI and ADSC groups showed improved calvarial bone defect healing compared to the control group. In addition, the ADSC+LPLI group showed significantly increased bone volume at 16 weeks after surgery. The area of new bone formation ranked as follows: control group < LPLI group < ADSC group < ADSC+LPLI group. There were significant differences between the groups. In addition, both ADSC and ADSC+LPLI groups showed strong signals of vWF expression. ADSC and LPLI treatments improved fracture repair in critical-sized calvarial defects in rats. Importantly, the combined treatment of ADSCs and LPLI further enhances the bone healing process.

Low-melt bioactive glass-reinforced 3D printing akermanite porous cages with highly improved mechanical properties for lumbar spinal fusion.

Although great strides have been made in medical technology, low back/neck pain and intervertebral disc degeneration initiated from disc degenerative disease remains a clinical challenge. Within the field of regenerative medicine therapy, we have sought to improve the biomechanical transformation of spinal fusion procedures conducted using biodegradable porous implants. Specifically, we have focused on developing mechanically strong bioceramic cages for spinal fusion and functional recovery. Herein, we fabricated the akermanite (AKE) ceramic-based porous cages using low-melting bioactive glass (BG) and 3D printing technology. The osteogenic cell adhesion on the cages was evaluated in vitro, and the spinal fusion was tested in the intervertebral disc trauma model. The results indicated that incorporation of 15% or 30% BG into AKE (i.e., AKE/BG15 and AKE/BG30) could enhance the compressive strength of bioceramic cages by 2- or 5-fold higher than the pure AKE cages (AKE/BG0). In comparison with porous β-tricalcium phosphate cages, the surface of AKE/BG15 and AKE/BG30 cages greatly promoted the growth and alkaline phosphatase expression of osteogenic cells. Histological and biomechanical analysis showed that the AKE/BG15 and AKE/BG30 readily stimulated the new bone tissue growth and improved the spinal biomechanics recovery. In the AKE/BG15 and AKE/BG30 cage groups, 4-6 of the rabbits demonstrated a successful fusion. In contrast, only 0-1 of the initial seeded AKE/BG0 and tricalcium phosphate cages resulted in fusion at 12weeks post-operatively. In summary, the akermanite-based cages showed an increased bone regenerative effect within an intervertebral disc trauma model, and thus, provided a promising candidate for improving spinal fusion surgery.

Microenvironment construction of strontium-calcium-based biomaterials for bone tissue regeneration: the equilibrium effect of calcium to strontium.

Strontium-doped calcium phosphate-based biomaterials have gained increased recognition due to their beneficial effects on bone formation. However, the underlying mechanism is still not clear. In this study, we detected the calcification effects of strontium-based materials on osteoblasts in vitro and bone formation in vivo. The results showed that strontium may inhibit bone cell function in osteoblasts under a standard calcium concentration (1.8 mM) by both reducing alkaline phosphatase activity and inhibiting absorption of osteopontin and osteocalcin. In contrast, a high calcium concentration (9 mM) enhances the bone regeneration effect of strontium-based materials. Cultured osteoblasts underwent increased proliferation, calcification and alkaline phosphatase activity upon increasing calcium concentrations. An experimental animal model was utilized to simulate a high calcium concentration microenvironment in bone tissue and low calcium concentration in the subcutaneous part and the in vivo results are similar to the in vitro results. These findings suggest that strontium only promoted an anabolic effect on osteoblasts to enhance osteogenesis in a calcium rich microenvironment. Strontium would inhibit bone regeneration under a low dose of calcium in vivo. Therefore, strontium seems to be a potentially effective therapeutic option for bone regeneration in combination with a high concentration environment of calcium ions. These results would provide an in-depth knowledge of an ion-based bone tissue substitute for bone regeneration.

HISTOMORPHOMETRIC ANALYSIS OF BONE REGENERATION AFTER USE OF PROPOLIS VERSUS NANOBONE GRAFT MATERIALS FOR THE MANAGEMENT OF CLASS II FURCATION DEFECTS IN DOGS

INTRODUCTION: Nanotechnology has been greatly utilized for bone regeneration strategies. It helps overcome some of the current limitations associated with bone regeneration methods Propolis is a natural substance made by the honeybee, it has effective antioxidant, antimicrobial, and anti-inflammatory effects. Moreover, it has multiple biological effects including improvement of wound healing and bone regeneration. OBJECTIVES: comparison of the effectiveness of NanoBone graft and propolis material on the inter-radicular bone regeneration in Mongrel dogs. MATERIALS AND METHODS: A split mouth design was carried out using the third and fourth mandibular premolars of 3 healthy mongrel dogs. A total of 12 grade II furcation defects were surgically created. The defects in the right side were treated with NanoBone graft and then a collagen membrane was used to cover the defects. In the left side the defects were treated with propolis and then covered with collagen membrane. The dogs were sacrificed after 4 weeks. Segments of the jaw bone containing the defects were then dissected out and prepared for histological evaluation. RESULTS: Both percentage of bone fill and percentage of bone surface area in defects treated with propolis powder were higher than those in NanoBone-filled defects. CONCLUSIONS: Both propolis and NanoBone graft materials have bone regenerative effects with higher ability of propolis to regenerate bone. KEYWORDS: Regeneration, Furcation, NanoBone, Bone graft, Propolis, Antioxidant.