Enriched mesoporous bioactive glass scaffolds as bone substitutes in critical diaphyseal bone defects in rabbits.

In the field of orthopedic surgery, there is an increasing need for the development of bone replacement materials for the treatment of bone defects. One of the main focuses of biomaterials engineering are advanced bioceramics like mesoporous bioactive glasses (MBG´s). The present study compared the new bone formation after 12 weeks of implantation of MBG scaffolds with composition 82,5SiO2-10CaO-5P2O5-x 2.5SrO alone (MBGA), enriched with osteostatin, an osteoinductive peptide, (MBGO) or enriched with bone marrow aspirate (MBGB) in a long bone critical defect in radius bone of adult New Zealand rabbits. New bone formation from the MBG scaffold groups was compared to the gold standard defect filled with iliac crest autograft and to the unfilled defect. Radiographic follow-up was performed at 2, 6, and 12 weeks, and microCT and histologic examination were performed at 12 weeks. X-Ray study showed the highest bone formation scores in the group with the defect filled with autograft, followed by the MBGB group, in addition, the microCT study showed that bone within defect scores (BV/TV) were higher in the MBGO group. This difference could be explained by the higher density of newly formed bone in the osteostatin enriched MBG scaffold group. Therefore, MBG scaffold alone and enriched with osteostatin or bone marrow aspirate increase bone formation compared to defect unfilled, being higher in the osteostatin group. The present results showed the potential to treat critical bone defects by combining MBGs with osteogenic peptides such as osteostatin, with good prospects for translation into clinical practice. STATEMENT OF SIGNIFICANCE: Treatment of bone defects without the capacity for self-repair is a global problem in the field of Orthopedic Surgery, as evidenced by the fact that in the U.S alone it affects approximately 100,000 patients per year. The gold standard of treatment in these cases is the autograft, but its use has limitations both in the amount of graft to be obtained and in the morbidity produced in the donor site. In the field of materials engineering, there is a growing interest in the development of a bone substitute equivalent. Mesoporous bioactive glass (MBG´s) scaffolds with three-dimensional architecture have shown great potential for use as a bone substitutes. The osteostatin-enriched Sr-MBG used in this long bone defect in rabbit radius bone in vivo study showed an increase in bone formation close to autograft, which makes us think that it may be an option to consider as bone substitute.

Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute promotes bone regeneration by moderating oxidative stress in osteoporotic bone defect.

The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and ß-Tricalcium Phosphate (ß-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo. Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. STATEMENT OF SIGNIFICANCE: Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into ß-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro. Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.

Comparison of different bone substitutes in the repair of rat calvaria critical size defects: questioning the need for alveolar ridge presentation.

OBJECTIVE: This study aimed to evaluate the effectiveness of biomaterials in bone healing of critical bone defects created by piezoelectric surgery in rat calvaria. METHOD AND MATERIALS: Histomorphologic analysis was performed to assess bone regeneration and tissue response. Fifty animals were randomized into five groups with one of the following treatments: Control group (n = 10), spontaneous blood clot formation with no bone fill; BO group (Bio-Oss, Geistlich Pharma; n = 10), defects were filled with bovine medullary bone substitute; BF group (Bonefill, Bionnovation; n = 10), defects were filled with bovine cortical bone substitute; hydroxyapatite group (n = 10), defects were filled with hydroxyapatite; calcium sulfate group (n = 10), defects were filled with calcium sulfate. Five animals from each group were euthanized at 30 and 45 days. The histomorphometry calculated the percentage of the new bone formation in the bone defect. RESULTS: All data obtained were evaluated statistically considering P < .05 as statistically significant. The results demonstrated the potential of all biomaterials for enhancing bone regeneration. The findings showed no statistical differences between all the biomaterials at 30 and 45 days including the control group without bone grafting. CONCLUSION: In conclusion, the tested biomaterials presented an estimated capacity of osteoconduction, statistically nonsignificant between them. In addition, the selection of biomaterial should consider the specific clinical aspect, resorption rates, size of the particle, and desired bone healing responses. It is important to emphasize that in some cases, using no bone filler might provide comparable results with reduced cost and possible complications questioning the very frequent use of ridge presentation procedures.

Repair of a rat calvaria defect with injectable strontium (Sr)-doped polyphosphate dicalcium phosphate dehydrate (P-DCPD) ceramic bone grafts.

The trace element strontium (Sr) enhances new bone formation. However, delivering Sr, like other materials, in a sustained manner from a ceramic bone graft substitute (BGS) is difficult. We developed a novel ceramic BGS, polyphosphate dicalcium phosphate dehydrate (P-DCPD), which delivers embedded drugs in a sustained pattern. This study assessed the in vitro and in vivo performance of Sr-doped P-DCPD. In vitro P-DCPD and 10%Sr-P-DCPD were nontoxic and eluents from 10%Sr-P-DCPD significantly enhanced osteoblastic MC3T3 cell differentiation. A sustained, zero-order Sr release was observed from 10%Sr-P-DCPD for up to 70 days. When using this BGS in a rat calvaria defect model, both P-DCPD and 10% Sr-P-DCPD were found to be biocompatible and biodegradable. Histologic data from decalcified and undecalcified tissue showed that 10%Sr-P-DCPD had more extensive new bone formation compared with P-DCPD 12-weeks after surgery and the 10%Sr-P-DCPD had more organized new bone and much less fibrous tissue at the defect margins. The new bone was formed on the surface of the degraded ceramic debris within the bone defect area. P-DCPD represented a promising drug-eluting BGS for repair of critical bone defects.

Surgical suction filter-derived bone graft displays osteogenic miRNA and mRNA patterns.

PURPOSE: Recently, a surgical suction filter device was introduced which aims at generating a suction filter-derived bone grafting substitute (SF-BGS). The osteogenic capacity of this grafting material, however, is unclear. MicroRNAs (miRNAs) and osteogenic mRNAs may influence these processes. The aim of this study was therefore to investigate the quality of the SF-BGS by determining the expression of miRNAs and osteogenic mRNAs. METHODS: Samples were collected during non-union surgery. Upon exposure of the intramedullary canal, the surgical vacuum system was fitted with the suction filter device containing collagen complex and synthetic ß-TCP: (Ca3(PO4)2, granule size 5-8 mm, total volume 10 mL (Cerasorb Foam®, Curasan AG, Kleinostheim, Germany). As a control, venous blood was used as in current clinical practice. Samples were snap-frozen and mechanically disrupted. MiRNAs and mRNAs were isolated, transcribed, and pooled for qPCR analysis. Lastly, mRNA targets were determined through in silico target analyses. RESULTS: The study population consisted of seven patients with a posttraumatic long bone non-union (4♀; mean age 54 ± 16 years). From the array data, distinct differences in miRNA expression were found between the SF-BGS and control samples. Osteogenic marker genes were overall upregulated in the SF-BGS. Qiagen IPA software identified 1168 mRNA targets for 43 of the overall deregulated miRNAs. CONCLUSION: This study revealed distinctly deregulated and exclusively expressed osteogenic miRNAs in SF-BGS, as well as overall enhanced osteogenic marker gene expression, as compared to the venous blood control group. These expression profiles were not seen in control samples, indicating that the derived material displays an osteogenic profile. It may therefore be a promising tool to generate a BGS or graft extender when needed.

Effect of different HA/ß-TCP coated 3D printed bioceramic scaffolds on repairing large bone defects in rabbits.

BACKGROUND: Treatment of large segmental bone defects is still a major clinical challenge, and bone grafting is the main method. The development of novel bone graft substitutes will help solve this problem. METHODS: Porous bioceramics hydroxyapatite (HA) scaffolds coated with different ratios of HA/ß-tricalcium phosphate (ß-TCP) were prepared by 3D printing. The scaffolds were sampled and tested in large segmental bone defect rabbit models. X-ray, micro-computed tomography (CT), hematoxylin and eosin (HE) staining, Van-Gieson staining, and type I collagen staining were performed to find the best scaffolds for large segmental bone defect treatment. RESULTS: The average length, diameter, compressive strength, and porosity of the bioceramics scaffolds were 15.05 ± 0.10 mm, 4.98 ± 0.06 mm, 11.11 ± 0.77 MPa, and 54.26 ± 5.38%, respectively. Postoperative lateral radiographs suggested the scaffold group got better bone healing and stability than the blank group. Micro-CT showed new bones grew into the scaffold from the two ends of the fracture along the scaffold and finally achieved bony union. The new bone volume around the scaffolds suggested the 3:7 HA/ß-TCP-coated bioceramic scaffolds were more favorable for the healing of large segmental bone defects. The results of HE, Van-Gieson, and type I collagen staining also suggested more new bone formation in 3:7 HA/ß-TCP-coated bioceramic scaffolds. CONCLUSION: 3:7 HA/ß-TCP-coated porous bioceramics scaffolds are more conducive to the repair of large bone defects in rabbits. The results of this study can provide some reference and theoretical support in this area.

Bone regeneration after maxillary sinus floor augmentation with different ratios of autogenous bone and deproteinized bovine bone mineral an in vivo experimental study.

OBJECTIVE: Test the hypothesis of no difference in bone regeneration after maxillary sinus floor augmentation (MSFA) with different ratios of iliac or mandibular autogenous bone (AB) graft and deproteinized bovine bone mineral (DBBM). MATERIALS AND METHODS: Forty minipigs were randomly allocated to bilateral MSFA using: (A) 100% AB, (B) 75% AB and 25% DBBM, (C) 50% AB and 50% DBBM, (D) 25% AB and 75% DBBM, or (E) 100% DBBM. The animals were euthanized 12 weeks after surgery. Percentage of bone, non-mineralized tissue, and residual DBBM were estimated by histomorphometric analysis in a randomly selected region of interest and summarized as mean percentage with 95% confidence interval (CI). RESULTS: Mean percentage of bone following MSFA with iliac or mandibular AB graft was: (A) 55.5% and 64.2%, (B) 60.3% and 61.6%, (C) 54.4% and 52.1%, (D) 51.8% and 53.1%, and (E) 47.6%, respectively. There was a significant trend toward a higher percentage of bone, with a higher ratio of AB within the graft (p < .01), regardless of the origin of AB graft (iliac or mandible). CONCLUSIONS: The hypothesis was rejected since percentage of bone was significantly increased with larger proportions of AB within the graft. Consequently, AB or a mixture of AB and diminutive quantities of DBBM seem to be the preferred graft for MSFA based solely on histomorphometric assessment. However, it should be emphasized that newly formed bone and residual AB graft particles could not be distinguished by the applied histologic procedure.

Combination of leukocyte and platelet-rich fibrin and demineralized bovine bone graft enhanced bone formation and healing after maxillary sinus augmentation: a randomized clinical trial.

BACKGROUND AND OBJECTIVE: The resorption of alveolar ridge bone and maxillary sinus pneumatization are challenges to implant-supported prosthetic rehabilitation. Bone regeneration using bone substitutes and growth factors are alternatives for maxillary sinus augmentation (MSA). Therefore, we sought to evaluate the effects of the association between leukocyte and platelet-rich fibrin (L-PRF) and deproteinized bovine bone mineral (DBBM) in MSA procedures. MATERIALS AND METHODS: Thirty-six maxillary sinuses from 24 individuals were included in this randomized clinical trial. The maxillary sinuses were randomly grafted with LPRF and DBBM (test group) or grafted only with DBBM (positive control). Dental implants were installed in the test group following two periods of evaluation: after 4 (DBBM+LPRF4) and 8 (DBBM+LPFR8) months of sinus graft healing, while the control group received implants only after 8 months. Cone beam computed tomography (CBCT) was taken 1 week after surgery (T1) and before implant placement (T2). Bone samples were collected during implant placement for histomorphometric and immunohistochemical (IHC) analysis. The primary implant stability was assessed by resonance frequency analysis. RESULTS: CBCT analysis demonstrated a significant decrease in bone volume from T1 to T2 in all groups without differences among them. Histologically, the test group showed significantly increase in bone neoformation in both periods of evaluation (LPRF+DBBM4: 44.70±14.01%; LPRF+DBBM8: 46.56±12.25%) compared to the control group (32.34±9.49%). The control group showed the highest percentage of residual graft. IHC analysis showed increased staining intensity of osteocalcin (OCN), vascular endothelial growth factor (VEGF), and runt related transcription factor 2 (RUNX-2) in LPRF+DBBM4 group, and osteopontin (OPN) in the L-PRF+DBBM8. Primary implant stability was successfully achieved (above 60 in implant stability quotient) in all the evaluated groups. CONCLUSION: Combination of L-PRF and DBBM increased and accelerated new bone formation allowing early implant placement probably due to the higher protein expression of RUNX2, VEGF, OCN, and OPN. These data suggest that the use of L-PRF might be an interesting alternative to use in combination with DBBM for augment the maxillary sinuses allowing the installation of appropriate length implants in shorter period of time. CLINICAL RELEVANCE: This study showed improvement in bone neoformation and accelerated healing when associating L-PRF and DBBM for maxillary sinus augmentation procedures. TRIAL REGISTRATION: This study was registered before participant recruitment in Brazilian Registry of Clinical Trials (ReBEC - RBR-95m73t).

Hierarchically Porous Implants Orchestrating a Physiological Viscoelastic and Piezoelectric Microenvironment for Bone Regeneration.

The extracellular matrix microenvironment of bone tissue comprises several physiological cues. Thus, artificial bone substitute materials with a single cue are insufficient to meet the demands for bone defect repair. Regeneration of critical-size bone defects remains challenging in orthopedic surgery. Intrinsic viscoelastic and piezoelectric cues from collagen fibers play crucial roles in accelerating bone regeneration, but scaffolds or implants providing integrated cues have seldom been reported. In this study, it is aimed to design and prepare hierarchically porous poly(methylmethacrylate)/polyethyleneimine/poly(vinylidenefluoride) composite implants presenting a similar viscoelastic and piezoelectric microenvironment to bone tissue via anti-solvent vapor-induced phase separation. The viscoelastic and piezoelectric cues of the composite implants for human bone marrow mesenchymal stem cell line stimulate and activate Piezo1 proteins associated with mechanotransduction signaling pathways. Cortical and spongy bone exhibit excellent regeneration and integration in models of critical-size bone defects on the knee joint and femur in vivo. This study demonstrates that implants with integrated physiological cues are promising artificial bone substitute materials for regenerating critical-size bone defects.

Bone Regeneration in Maxillary Sinus Augmentation Using Advanced Platelet-Rich Fibrin (A-PRF) and Plasma Rich in Growth Factors (PRGF): A Pilot Randomized Controlled Trial

The purpose of this pilot randomized controlled trial was to analyze and compare the effects of advanced platelet-rich fibrin (A-PRF) and plasma rich in growth factors (PRGF) combined with deproteinized bovine bone mineral (DBBM) on bone regeneration outcomes in maxillary sinus augmentation (MSA) procedures. A total of 15 patients in need of MSA were consecutively recruited. Maxillary sinuses were grafted with DBBM alone (control group), DBBM mixed with A-PRF (PRF group), or DBBM mixed with PRGF (PRGF group). After a 6-month healing period, bone core biopsy samples were collected prior to implant placement for histologic and histomorphometric analyses. The mean percentage of mineralized tissue (MT) was 20.33 ± 11.50 in the control group, 32.20 ± 7.29 for the PRF group, and 34.80 ± 6.83 for the PRGF group, with no statistically significant differences across the three groups (P > .05). The mean percentage of remaining bone grafting material (RBGM) was 24.00 ± 7.94 for the control group, 26.00 ± 7.78 for the PRF group, and 15.80 ± 8.23 for the PRGF group, with no statistically significant differences across the three groups (P > .05). Finally, the mean percentage of nonmineralized tissue (NMT) was 55.66 ± 7.77 for the control group, 41.40 ± 8.32 for the PRF group, and 49.60 ± 5.68 for the PRGF group, with no statistically signifcant differences across the three groups (P > .05). These findings suggest that the addition of A-PRF and PRGF to DBBM does not enhance new bone formation outcomes in maxillary sinus augmentation procedures. Neither of the two platelet concentrates were superior to the other in any of the variables assessed.

Epigallocatechin-3-gallate improves the biocompatibility of bone substitutes in dental pulp stem cells.

BACKGROUND: The Biocompatibility between osteoprogenitor cells and bone substitutes is necessary for cell differentiation and osteogenesis. The aim of this study was to assess the in vitro effect of bovine (Geistlich BioOss®), porcine (OsteoBiol Gen-Os®) and beta-tricalcium phosphate (Cerasorb M®) bone substitutes, and their combination with polyphenol epigallocatechin-3-gallate (EGCG), upon cultured dental pulp stem cells (DPSCs). METHODS: The DPSCs were isolated from third molars extracted from healthy individuals and seeded with 5 mg/ml of Bio-Oss® (BO), Gen-Os® (GO) and Cerasorb® (CE) in combination with EGCG 1 µM. The effects were evaluated based on cell viability / cytotoxicity assay (MTT, cell viability staining test), cell migration, scanning electron microscopy (SEM), and alkaline phosphatase (ALP) activity. RESULTS: BO and CE produced negative effects upon cell viability and migration, and GO and CE resulted in deficient cell adhesion. On the other hand, all the biomaterials exerted no negative effects upon ALP activity. Interestingly, the addition of EGCG reverted the cytotoxic effect and the loss of migration capacity in the BO and CE groups, and improved cell adhesion in the GO and CE groups. Furthermore, EGCG promoted an overall increased in ALP activity. CONCLUSION: The addition of EGCG to the tested biomaterials BO, GO and CE reverts their negative impact on DPSCs, and improves their biocompatibility with cultured DPSCs. The use of EGCG, thus, appears to be a promising strategy for restoring and enhancing the osteoconductive properties of BO, GO and CE in bone regeneration treatments.

Preparation, physicochemical characterization, and in vitro and in vivo osteogenic evaluation of a bioresorbable, moldable, hydroxyapatite/poly(caprolactone-co-lactide) bone substitute.

Use of bioresorbable artificial bone substitutes is anticipated for bone augmentation in dental implant surgery because they are relatively economical and uniform in quality compared to heterogeneous bone. In this study, a new shapable, rubbery, bioresorbable bone substitute was developed. The material was prepared by ultrasonically dispersing hydroxyapatite (HA) particles throughout a poly (caprolactone-co-lactide) (PCLLA) rubbery matrix. Physiochemical properties of the bone substitute including its composition, deformability, anti-collapse ability, degradation behavior, and in vitro and in vivo osteogenic ability were evaluated. Results revealed that HA/PCLLA, which consists of homogeneously dispersed HA particles and a rubbery matrix composed of PCLLA, possesses a deformable capacity. The result of the mass retention rate of the material indicated an excellent durability in an aqueous environment. Further, the effects of HA/PCLLA on cell functions and bone-regenerated performance were evaluated in vitro and in vivo. The results showed that HA/PCLLA had enhanced proliferative capacity, and ability to undergo osteogenic differentiation and mineralization in vitro. It was also found that HA/PCLLA had an appropriate degradation rate to induce consecutive new bone formation without collapse at the early stage in vivo, as well as the ability to maintain the contour of the bone-grafting area, which is comparable to the deproteinized bovine bone mineral. These results indicated that HA/PCLLA is a promising bioresorbable bone substitute with properties that meet clinical requirements, including deformability, resistance to collapse in an aqueous environment, appropriate early-stage degradation rate, biocompatibility, osteogenic bioactivity and the capacity to regenerate bone tissue with favorable contour.

Standard in vitro evaluations of engineered bone substitutes are not sufficient to predict in vivo preclinical model outcomes.

Understanding the optimal conditions required for bone healing can have a substantial impact to target the problem of non-unions and large bone defects. The combination of bioactive factors, regenerative progenitor cells and biomaterials to form a tissue engineered (TE) complex is a promising solution but translation to the clinic has been slow. We hypothesized the typical material testing algorithm used is insufficient and leads to materials being mischaracterized as promising. In the first part of this study, human bone marrow - derived mesenchymal stromal cells (hBM-MSCs) were embedded in three commonly used biomaterials (hyaluronic acid methacrylate, gelatin methacrylate and fibrin) and combined with relevant bioactive osteogenesis factors (dexamethasone microparticles and polyphosphate nanoparticles) to form a TE construct that underwent in vitro osteogenic differentiation for 28 days. Gene expression of relevant transcription factors and osteogenic markers, and von Kossa staining were performed. In the second and third part of this study, the same combination of TE constructs were implanted subcutaneously (cell containing) in T cell-deficient athymic Crl:NIH-Foxn1rnu rats for 8 weeks or cell free in an immunocompetent New Zealand white rabbit calvarial model for 6 weeks, respectively. Osteogenic performance was investigated via MicroCT imaging and histology staining. The in vitro study showed enhanced upregulation of relevant genes and significant mineral deposition within the three biomaterials, generally considered as a positive result. Subcutaneous implantation indicates none to minor ectopic bone formation. No enhanced calvarial bone healing was detected in implanted biomaterials compared to the empty defect. The reasons for the poor correlation of in vitro and in vivo outcomes are unclear and needs further investigation. This study highlights the discrepancy between in vitro and in vivo outcomes, demonstrating that in vitro data should be interpreted with extreme caution. In vitro models with higher complexity are necessary to increase value for translational studies. STATEMENT OF SIGNIFICANCE: Preclinical testing of newly developed biomaterials is a crucial element of the development cycle. Despite this, there is still significant discrepancy between in vitro and in vivo test results. Within this study we investigate multiple combinations of materials and osteogenic stimulants and demonstrate a poor correlation between the in vitro and in vivo data. We propose rationale for why this may be the case and suggest a modified testing algorithm.

An assessment of physical properties and the viability of osteoblast-like cells of cefazolin-impregnated calcium sulfate bone-void filler.

Calcium sulfate, an injectable and biodegradable bone-void filler, is widely used in orthopedic surgery. Based on clinical experience, bone-defect substitutes can also serve as vehicles for the delivery of drugs, for example, antibiotics, to prevent or to treat infections such as osteomyelitis. However, antibiotic additions change the characteristics of calcium sulfate cement. Moreover, high-dose antibiotics may also be toxic to bony tissues. Accordingly, cefazolin at varying weight ratios was added to calcium sulfate samples and characterized in vitro. The results revealed that cefazolin changed the hydration reaction and prolonged the initial setting times of calcium sulfate bone cement. For the crystalline structure identification, X-ray diffractometer revealed that cefazolin additive resulted in the decrease of peak intensity corresponding to calcium sulfate dihydrate which implying incomplete phase conversion of calcium sulfate hemihydrate. In addition, scanning electron microscope inspection exhibited cefazolin changed the morphology and size of the crystals greatly. A relatively higher amount of cefazolin additive caused a faster degradation and a lower compressive strength of calcium sulfate compared with those of uploaded samples. Furthermore, the extract of cefazolin-impregnated calcium sulfate impaired cell viability, and caused the death of osteoblast-like cells. The results of this study revealed that the cefazolin additives prolonged setting time, impaired mechanical strength, accelerated degradation, and caused cytotoxicity of the calcium sulfate bone-void filler. The aforementioned concerns should be considered during intra-operative applications.

Screening of Hydroxyapatite Biomaterials for Alveolar Augmentation Using a Rat Calvaria Critical-Size Defect Model: Bone Formation/Maturation and Biomaterials Resolution.

BACKGROUND: Natural (bovine-/equine-/porcine-derived) or synthetic hydroxyapatite (HA) biomaterials appear to be the preferred technologies among clinicians for bone augmentation procedures in preparation for implant dentistry. The aim of this study was to screen candidate HA biomaterials intended for alveolar ridge augmentation relative to their potential to support local bone formation/maturation and to assess biomaterial resorption using a routine critical-size rat calvaria defect model. METHODS: Eighty adult male Sprague Dawley outbred rats obtained from a approved-breeder, randomized into groups of ten, were used. The calvaria defects (ø8 mm) either received sham surgery (empty control), Bio-Oss (bovine HA/reference control), or candidate biomaterials including bovine HA (Cerabone, DirectOss, 403Z013), and bovine (403Z014) or synthetic HA/ß-TCP (Reprobone, Ceraball) constructs. An 8 wk healing interval was used to capture the biomaterials' resolution. RESULTS: All biomaterials displayed biocompatibility. Strict HA biomaterials showed limited, if any, signs of biodegradation/resorption, with the biomaterial area fraction ranging from 22% to 42%. Synthetic HA/ß-TCP constructs showed limited evidence of biodegradation/erosion (biomaterial area fraction ≈30%). Mean linear defect closure in the sham-surgery control approximated 40%. Mean linear defect closure for the Bio-Oss reference control approximated 18% compared with 15-35% for the candidate biomaterials without significant differences between the controls and candidate biomaterials. CONCLUSIONS: None of the candidate HA biomaterials supported local bone formation/maturation beyond the native regenerative potential of this rodent model, pointing to their limitations for regenerative procedures. Biocompatibility and biomaterial dimensional stability could suggest their potential utility as long-term defect fillers.

Addition of Synthetic Biomaterials to Deproteinized Bovine Bone Mineral (DBBM) for Bone Augmentation-A Preclinical In Vivo Study.

(1) Aim: To investigate the effect of synthetic bone substitutes, α-tricalcium phosphate (α-TCP) or bi-layered biphasic calcium-phosphate (BBCP) combined with deproteinized bovine bone mineral (DBBM), on bone formation. (2) Methods: Thirty critical size defects were randomly treated with the following five different treatment modalities: (1) negative control (NC, empty), (2) DBBM, (3) α-TCP + DBBM (1:1), (4) BBCP 3%HA/97%α-TCP + DBBM (1:1), and (5) BBCP 6%HA/94%α-TCP + DBBM (1:1). The samples, at four weeks post-surgery, were investigated by micro-CT and histological analysis. (3) Results: A similar level of new bone formation was demonstrated in the DBBM with α-TCP bone substitute groups when compared to the negative control by histomorphometry. DBBM alone showed significantly lower new bone area than the negative control (p = 0.0252). In contrast to DBBM, the micro-CT analysis revealed resorption of the α-TCP + DBBM, BBCP 3%HA/97%α-TCP + DBBM and BBCP 6%HA/94%α-TCP + DBBM, as evidenced by a decrease of material density (p = 0.0083, p = 0.0050 and p = 0.0191, respectively), without changing their volume. (4) Conclusions: New bone formation was evident in all defects augmented with biomaterials, proving the osteoconductive properties of the tested material combinations. There was little impact of the HA coating degree on α-TCP in bone augmentation potential and material resorption for four weeks when mixed with DBBM.

Biological Impact of Alloplastic Bone Graft vs Bovine Xenograft and Allograft Materials in Bone Healing: An Experimental Study.

AIM: This study aims to compare the performance of beta-tricalcium phosphate with calcium sulfate (ß-TCP/CS) vs a bovine xenograft, freeze-dried mineralized allograft, and spontaneous healing in surgically prepared bone defects in rabbit tibia. MATERIALS AND METHODS: The grafting materials were implanted in three out of four standardized monocortical bony defects, 3-mm diameter and 3-mm deep, in rabbit tibia while one defect was left empty for spontaneous healing as a control group. Twelve rabbits were euthanized at 2 and 6 weeks after surgery. The bone tissue specimens were histologically evaluated using hematoxylin and eosin, Masson's trichrome and osteoprotegrin (OPG) immunohistochemical staining. Results were quantitatively evaluated. RESULTS: An enhancement of bone healing was noticed in the defects grafted with ß-TCP/CS compared with all other groups at 2 and 6 weeks after surgery as it showed significant increase in OPG expression and a significant decrease in the amount of collagen at 6 weeks after surgery. The residual grafted particles were the least with ß-TCP/CS at 6 weeks after surgery. CONCLUSION: The ß-TCP/CS grafting material is a promising bioactive alloplastic bone substitute as it proved to be biocompatible, osteoconductive, and bioresorbable bone substitute. CLINICAL SIGNIFICANCE: The ß-TCP/CS grafting material can be used for guided bone regeneration resulting in pronounced high-quality bone which aids in oral and maxillofacial reconstruction.

Microporous surface containing flower-like molybdenum disulfide submicro-spheres of sulfonated polyimide with antibacterial effect and promoting bone regeneration and osteointegration.

Implanted materials with both osteogenic and antibacterial functions are promising for facilitating osteointegration and preventing infection for orthopedic applications. In this work, we synthesized flower-like molybdenum disulfide (fMD) submicro-spheres containing nanosheets, which were incorporated onto the microporous surface of polyimide (PI) via concentrated sulfuric acid, suspending fMD contents of 5 wt% (SPM1) and 10 wt% (SPM2). Compared with sulfonated polyimide (SPM0), both SPM1 and SPM2 with microporous surfaces containing fMD exhibited nano-submicro-microporous surfaces, which improved the surface roughness, wettability, and surface energy. Due to there being more fMD submicro-spheres on the microporous surface, SPM2 revealed a better antibacterial effect than SPM1. In addition, compared with SPM1 and SPM0, SPM2 with more fMD significantly promoted rat bone marrow-derived stromal cell response in vitro. Moreover, SPM2 remarkably enhanced new bone formation and osteointegration in vivo. In summary, the combination of fMD with the microporous surface of SPM2 resulted in a nano-submicro-microporous surface with optimized surface performance, which possessed not only osteogenic bioactivity but also an antibacterial effect. As a bone implant, SPM2 with osteogenic and antibacterial functions may have enormous potential as a bone tissue substitute.

[Augmentation in surgical sepsis : Chances and limitations in the treatment of osteitis with calcium hydroxyapatite containing antibiotics]. / Augmentation in der septischen Chirurgie : Chancen und Limitationen in der Behandlung der Osteitis mit antibiotikahaltigem Kalziumhydroxylapatit.

BACKGROUND: The surgical treatment of osteitis or fracture-related infections (FRI) is often associated with large bone defects. The treatment of these defects remains a major challenge in trauma surgery. Within the concept of tissue engineering, the development of various hybrid bone graft substitutes, such as calcium hydroxyapatite with added antibiotics, is continuously progressing. OBJECTIVE: Chances and limitations in the treatment of osteitis with calcium hydroxyapatite containing antibiotics. MATERIAL AND METHODS: Overview of the results of a 2-stage (infection) pseudarthrosis model on rat femurs treated with Cerament® G (Bonesupport, Lund, Schweden). Evaluation of the clinical experiences based on three case examples of osteitis treated with calcium hydroxyapatite containing antibiotics (Cerament® G or Cerament® V). RESULTS: After establishment of a 2­stage pseudarthrosis model on the rat femur, the osteoconductive and osteoinductive potential of calcium hydroxyapatite containing antibiotics could be confirmed. In the clinical application, the use of Cerament® G seems to lead to a more favorable outcome in small cavitary defects. The recurrence rates are higher than previously described, especially for larger segmental defects. CONCLUSION: Taking the clinical and experimental results into consideration, a stricter evaluation of the indications for the use of Cerament® G is necessary to achieve the best possible outcome for patients.

Comparison of periodontal wound healing/regeneration by recombinant human fibroblast growth factor-2 combined with ß-tricalcium phosphate, carbonate apatite, or deproteinized bovine bone mineral in a canine one-wall intra-bony defect model.

AIM: To evaluate periodontal wound healing/regeneration of one-wall intra-bony defects treated with recombinant human fibroblast growth factor-2 (rhFGF-2) and beta-tricalcium phosphate (ß-TCP), carbonate apatite (CO3 Ap), or deproteinized bovine bone mineral (DBBM) in dogs. MATERIALS AND METHODS: The stability of rhFGF-2 adsorbed onto the bone substitutes was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). One-wall intra-bony defects (5 × 5 × 5 mm) created in five adult male beagle dogs were treated with rhFGF-2 alone (rhFGF-2), rhFGF-2 with ß-TCP (rhFGF-2/ß-TCP), rhFGF-2 with CO3 Ap (rhFGF-2/CO3 Ap), or rhFGF-2 with DBBM (rhFGF-2/DBBM). Histological outcomes (e.g., linear length of new cementum adjacent to the newly formed bone with inserting collagen fibres [NA] as the primary outcome) were evaluated at 10 weeks post surgery. RESULTS: Significantly higher amount of rhFGF-2 was adsorbed onto CO3 Ap compared with ß-TCP. Among the treatment groups, the rhFGF-2/DBBM group showed the highest amount of periodontal tissue regeneration. The rhFGF-2/DBBM group showed significantly greater formation of NA (3.22 ± 0.40 mm) compared with rhFGF-2 (1.17 ± 1.00 mm, p < .01) group. Additionally, new bone area in the rhFGF-2/DBBM group (9.78 ± 2.30 mm2 ) was significantly higher than that in the rhFGF-2 (5.08 ± 1.26 mm2 , p < .01), rhFGF-2/ß-TCP (5.91 ± 1.27 mm2 , p < .05), and rhFGF-2/CO3 Ap (6.51 ± 1.49 mm2 , p < .05) groups. Slight ankylosis was found in the rhFGF-2/ß-TCP (1/9 sites), rhFGF-2/CO3 Ap (3/10 sites), and rhFGF-2/DBBM (1/9 sites) groups. CONCLUSIONS: Within their limitations, the present data indicate that DBBM seems to be a suitable carrier for rhFGF-2 and that rhFGF-2/DBBM treatment promotes favourable periodontal regeneration compared with rhFGF-2, rhFGF-2/ß-TCP, and rhFGF-2/CO3 Ap treatments in one-wall intra-bony defects.