Efficacy Of Bone Regeneration Research Articles

Mechanical properties and effect on osteodifferentiation of induced pluripotent stem cells of chitosan/whisker/calcium phosphate cement composite biomaterial

To investigate the mechanical properties of the novel compound calcium phosphate cement (CPC) biological material as well as the biological activity and osteogenesis effects of induced pluripotent stem cells (iPS) seeding on scaffold and compare their bone regeneration efficacy in cranial defects in rats. Ac- cording to the different scaffold materials, the experiment was divided into 4 groups: pure CPC scaffold group (group A), CPC∶10% wt chitosan as 2∶1 ratio mixed scaffold group (group B), CPC∶10% wt chitosan∶whisker as 2∶1∶1 ratio mixed scaffold group (group C), and CPC∶10% wt chitosan∶whisker as 2∶1∶2 ratio mixed scaffold group (group D). Mechanical properties (bending strength, work-of-fracture, hardness, and modulus of elasticity) of each scaffold were detected. The scaffolds were cultured with fifth generation iPS-mesenchymal stem cells (MSCs), and the absorbance ( A) values of each group were detected at 1, 3, 7, and 14 days by cell counting kit 8 (CCK-8) method; the alkaline phosphatase (ALP) activity, Live/Dead fluorescence staining and quantitative detection, ALP, Runx2, collagen typeⅠ, osteocalcin (OC), and bone morphogenetic protein 2 (BMP-2) gene expressions by RT-PCR were detected at 1, 7, and 14 days; and the alizarin red staining were detected at 1, 7, 14, and 21 days. Twenty-four 3-month-old male Sprague Dawley rats were used to establish the 8 mm-long skull bone defect model, and were randomly divided into 4 groups ( n=6); 4 kinds of scaffold materials were implanted respectively. After 8 weeks, HE staining was used to observe the repair of bone defects and to detect the percentage of new bone volume and the density of neovascularization. The bending strength, work-of-fracture, hardness, and modulus of elasticity in groups B, C, and D were significantly higher than those in group A, and in groups C, D than in group B, and in group D than in group C ( P<0.05). CCK-8 assay showed that cell activity gradually increased with the increase of culture time, the A values in groups B, C, and D at 3, 7, 14 days were signifiantly higher than those in group A, and in groups C, D than in group B ( P<0.05), but no significant difference was found between groups C and D ( P>0.05). Live/Dead fluorescence staining showed that the proportion of living cells in groups B, C, and D at 7 and 14 days was significantly higher than that in group A ( P<0.05), and in groups C, D at 7 days than in group B ( P<0.05); but no significant difference was found between groups C and D ( P>0.05). RT-PCR showed that the relative expressions of genes in groups B, C, and D at 7 and 14 days were significantly higher than those in group A, and in groups C, D than in group B ( P<0.05); but no significant difference was found between groups C and D ( P>0.05). Alizarin red staining showed that the red calcium deposition on the surface of scaffolds gradually deepened and thickened with the prolongation of culture time; the A values in groups B, C, and D at 14 and 21 days were significantly higher than those in group A ( P<0.05), and in groups C and D than in group B ( P<0.05), but no significant difference was found between groups C and D ( P>0.05). In vivo repair experiments in animals showed that the new bone in each group was mainly filled with the space of scaffold material. Osteoblasts and neovascularization were surrounded by new bone tissue in the matrix, and osteoblasts were arranged on the new bone boundary. The new bone in groups B, C, and D increased significantly when compared with group A, and the new bone in groups C and D was significantly higher than that in group B. The percentage of new bone volume and the density of neovascularization in groups B, C, and D were significantly higher than those in group A, and in groups C and D than in group B ( P<0.05); but no significant difference was found between groups C and D ( P>0.05). The mechanical properties of the new reinforced composite scaffold made from composite chitosan, whisker, and CPC are obviously better than that of pure CPC scaffold material, which can meet the mechanical properties of cortical bone and cancellous bone. iPS-MSCs is attaching and proliferating on the new reinforced composite scaffold material, and the repair effect of bone tissue is good. It can meet the biological and osteogenic activity requirements of the implant materials in the bone defect repair.

Design and development of novel hyaluronate-modified nanoparticles for combo-delivery of curcumin and alendronate: fabrication, characterization, and cellular and molecular evidences of enhanced bone regeneration

Osteoporosis is a medical condition of fragile bones with an increased susceptibility to fracture. Despite having availability of a wide range of pharmacological agents, prevalence of osteoporosis is continuously escalating. Owing to excellent biomedical achievements of nanomedicines in the last few decades, we aimed combo-delivery of bone anti-resorptive agent, alendronate (ALN), and bone density enhancing drug, curcumin (CUR) in the form of polymeric nanoparticles. To further optimize the therapeutic efficacy, the prepared ALN/CUR nanoparticles (NPs) were decorated with hyaluronic acid (HA) which is a well-documented biomacromolecule having exceptional bone regenerating potential. The optimized nanoformulation was then evaluated for bone regeneration efficacy by assessing time-mannered modulation in the proliferation, differentiation, and mineralization of MC3T3-E1 cells, a pre-osteoblastic model. Moreover, the time-mannered expression of various bone-forming protein biomarkers such as bone morphogenetic protein, runt related transcription factor 2, and osteocalcin were assessed in the cell lysates. Results revealed that HA-ALN/CUR NPs provoke remarkable increase in the proliferation, differentiation, and mineralization in the ECM of MC3T3-E1 cells which ultimately leads to enhanced bone formation. This new strategy of employing simultaneous delivery of anti-resorptive and bone forming agents would open new horizons for scientists as an efficient alternative pharmacotherapy for the management of osteoporosis.

Efficacy of Bone Regeneration using Micro-graft Suspension of Palatal Mucosa in Rats

Efficacy of Bone Regeneration using Micro-graft Suspension of Palatal Mucosa in Rats

Promotion of bone regeneration on titanium implants through a chemical treatment process using calcium phosphate slurry: Microscopic analysis, cellular response, and animal experiment.

The present study provides scientific evidence that a new chemical treatment process using calcium phosphate slurry promotes bone regeneration on titanium (Ti) implants. The material's surface modified by the treatment was analyzed using microscopic observation and the bone regeneration efficacy was evaluated both in vitro and in vivo. Formation of a thin hydroxyapatite layer with a thickness of about 50 nm and an increase of surface roughness were confirmed by microscopic observations. Histological evaluation of rat femora implanted with the specimens showed that the areas of the specimens directly attached to bone tissue were significantly more extensive than those implanted with control Ti at 2 and 8 weeks. Likewise, on the treated Ti, ALP activity, osteopontin, osteocalcin, and calcium contents of rat bone marrow stromal cells were significantly higher than on the control Ti. Furthermore, reverse transcription polymerase chain reaction showed greater expression of messenger ribonucleic acid encoding Cbfa1 and collagen type1 on the treated Ti at 2 weeks. Based on these results, we concluded that the new process was effective to enhance the osteoconductivity of Ti. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2716-2724, 2018.

Stem cell-based bone regeneration in diseased microenvironments: Challenges and solutions

Restoration of extensive bone loss and defects remain as an unfulfilled challenge in modern medicine. Given the critical contributions to bone homeostasis and diseases, mesenchymal stem cells (MSCs) have shown great promise to jumpstart and facilitate bone healing, with immense regenerative potential in both pharmacology-based endogenous MSC rescue/mobilization in skeletal diseases and emerging application of MSC transplantation in bone tissue engineering and cytotherapy. However, efficacy of MSC-based bone regeneration was not always achieved; particularly, fulfillment of MSC-mediated bone healing in diseased microenvironments of host comorbidities remains as a major challenge. Indeed, impacts of diseased microenvironments on MSC function rely not only on the dynamic regulation of resident MSCs by surrounding niche to convoy pathological signals of bone, but also on the profound interplay between transplanted MSCs and recipient components that mediates and modulates therapeutic effects on skeletal conditions. Accordingly, novel solutions have recently been developed, including improving resistance of MSCs to diseased microenvironments, recreating beneficial microenvironments to guarantee MSC-based regeneration, and usage of subcellular vesicles of MSCs in cell-free therapies. In this review, we summarize state-of-the-art knowledge regarding applications and challenges of MSC-mediated bone healing, further offering principles and effective strategies to optimize MSC-based bone regeneration in aging and diseases.

Composite Scaffolds of Mineralized Natural Extracellular Matrix on True Bone Ceramic Induce Bone Regeneration Through Smad1/5/8 and ERK1/2 Pathways.

A stem cell-derived mineralized extracellular matrix (ECM) may be a good strategy to endow scaffolds with a bone microenvironment, thus inducing bone regeneration. However, it also faces some challenges, such as limited number of cells, additional wound for autologous cell isolation, and time consumption of cell expansion. In this study, we designed a novel tissue-derived ECM scaffold fabricated by depositing porcine small intestinal submucosa (SIS) ECM on true bone ceramic (TBC), which was followed by mineralization treatment (mSIS/TBC). In vitro, compared with pure TBC, mSIS/TBC promoted cell proliferation, cell viability, and osteoblastic differentiation of the newly seeded rat bone marrow mesenchymal stem cells (BMSCs), and upregulation of the messenger RNA (mRNA) level of osteogenesis-related genes. Western blot assay revealed that mSIS/TBC enhanced osteoblastic differentiation through activation of phosphorylated Smad1/5/8 and phosphorylated extracellular signal-regulated kinase (ERK), as an underlying mechanism. In vivo, in a rat cranial critical size defect model, mSIS/TBC scaffolds induced greater bone formation than pure TBC scaffolds. Meanwhile, a comparative study on the capacity of bone regeneration was also carried out between mSIS/TBC and BMSC-derived ECM deposited on TBC scaffold in vivo and in vitro. The results demonstrated that mSIS/TBC scaffolds acquired a comparable bone regeneration efficacy to that of BMSC-derived ECM deposited on TBC scaffolds. Collectively, our results demonstrated that mSIS/TBC enhanced bone regeneration by supporting cell proliferation and cell viability, and by activating Smad1/5/8 and ERK1/2 signal pathways of BMSC in vitro and in vivo; thus, mSIS/TBC is an excellent alternative to stem cell-derived ECM scaffold for bone regeneration.

Dehydrothermally Cross-Linked Collagen Membrane with a Bone Graft Improves Bone Regeneration in a Rat Calvarial Defect Model.

In this study, the bone regeneration efficacy of dehydrothermally (DHT) cross-linked collagen membrane with or without a bone graft (BG) material was evaluated in a critical-sized rat model. An 8-mm-diameter defect was created in the calvaria of 40 rats, which were randomized into four groups: (1) control; (2) DHT; (3) BG; and, (4) DHT + BG. Evaluations were made at 2 and 8 weeks after surgery using micro-computed tomographic (micro-CT), histological, and histomorphometric analyses. Micro-CT analysis showed an increase in the new bone volume (NBV) of the BG and DHT + BG groups at 2 weeks after surgery, representing a significant difference (p < 0.05). At 8 weeks after surgery, the NBV increased in all four groups. However, larger NBVs were observed in the BG and DHT + BG groups, and a significant difference was no longer observed between the two groups. Histologic analysis demonstrated that the graft materials sustained the center of the defect in the BG and DHT + BG groups, which was shown in histomorphometric analysis as well. These results suggest that DHT membrane is a safe biomaterial with adequate tissue integration, and has a positive effect on new bone formation. Moreover, the best effects were achieved when DHT was used in conjunction with BG materials.

Enhanced bone formation in the vicinity of porous β-TCP scaffolds exhibiting slow release of collagen-derived tripeptides.

It has been experimentally proven that orally ingested collagen-derived tripeptides (Ctp) are quickly absorbed in the body and effectively promote the regeneration of connective tissues including bone and skin. Ctp are capable to activate osteoblasts and fibroblasts, which eventually promotes tissue regeneration. Based on these findings, a hypothesis was formulated in this study that direct delivery of Ctp to bone defect would also facilitate tissue regeneration as well as oral administration. To test the hypothesis, we prepared a bone augmentation material with the ability to slowly release Ctp, and investigated its in vivo bone regeneration efficacy. The implant material was porous β-tricalcium phosphate (β-TCP) scaffold which was coated with a co-precipitated layer of bone-like hydroxyapatite and Ctp. The β-TCP was impregnated with approximately 0.8%(w/w) Ctp. Then, the Ctp-modified β-TCP was implanted into bone defects of Wistar rats to evaluate in vivo efficacy of Ctp directly delivered from the material to the bone defects. The control was pristine porous β-TCP. In vitro tests showed that Ctp were steadily released from the co-precipitated layer for approximately two weeks. The Ctp-modified scaffolds significantly promoted new bone formation in vivo in their vicinity as compared with pristine β-TCP scaffolds; 6 weeks after the implantation, Ctp-modified scaffolds promoted twice as much bone formation as the control implants. Consequently, we achieved the slow and steady release of Ctp, and found that direct delivery of Ctp from implant materials was effective for bone regeneration as well as oral administration. A β-TCP scaffold capable of slowly releasing bone-enhancing substances significantly promoted bone formation.

骨髄由来間葉系幹細胞を用いて合成ポリペプチドPoly(Pro-Hyp-Gly)スポンジを足場とした骨再生の有効性(大阪歯科大学大学院歯学研究科博士(歯学)学位論文内容要旨および論文審査結果要旨の公表)

骨髄由来間葉系幹細胞を用いて合成ポリペプチドPoly(Pro-Hyp-Gly)スポンジを足場とした骨再生の有効性(大阪歯科大学大学院歯学研究科博士(歯学)学位論文内容要旨および論文審査結果要旨の公表)

Priming Adipose Stem Cells with Tumor Necrosis Factor-Alpha Preconditioning Potentiates Their Exosome Efficacy for Bone Regeneration.

Mesenchymal stem cells (MSCs) have been widely used for tissue repair and regeneration. However, the inherent drawbacks, including limited cell survival after cell transplantation, have hindered direct MSC transplantation for tissue repair and regeneration. The aim of this study was to investigate if exosomes isolated from MSCs can promote the proliferation and differentiation of human primary osteoblastic cells (HOBs) and be potentially used for bone tissue regeneration. We showed that adipose tissue-derived MSC (ASC)-derived exosomes (ASC-EXO) were able to promote the proliferation and osteogenic differentiation in HOBs; and the trophic effects of ASC-EXO on HOBs were further harnessed when ASCs were preconditioned with tumor necrosis factor-alpha (TNF-α) for 3 days, which mimics the acute inflammatory phase upon bone injury. In addition, we showed that Wnt-3a content was elevated in ASC-EXO when ASCs were preconditioned by TNF-α, and inhibiting Wnt signaling decreased the osteogenic gene expression levels in HOBs which were cultured in TNF-α preconditioned ASCs conditioned medium. In conclusion, it was demonstrated that ASC-EXO, especially primed by TNF-α preconditioning on ASCs, offer a promising approach to replace direct stem cell transplantation for bone repair and regeneration.

“Evaluation of wound healing and bone regeneration using autologous platelet-rich plasma and platelet-rich fibrin postextractions”: A comparative study

Introduction: It has already been established in the past that platelets play a major role in wound healing. Platelet- rich plasma (PRP) and Platelet- rich fibrin (PRF) are autologous concentrates of platelets in a relatively small volume of plasma and they enable delivery of growth factors in increased amounts to surgical sites to promote wound healing. Aims and Objectives: This study focuses on comparing the two platelet concentrates – platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) as graft materials in extraction sockets and their efficacy in wound healing and bone regeneration. Materials and Methods: Sixty patients requiring extraction of unilateral third molars were considered. Computer-generated random allocation of subjects was done. Group A: PRP was used as the graft material in the third molar extraction socket Group B: PRF was used as the graft material in the third molar extraction socket Group C: No material was used as graft in the third molar extraction socket. Soft tissue healing and bone healing were assessed in the postoperative follow up visits. Results: We observed that Group B showed significantly improved soft tissue healing and a faster bone healing as compared to Group A. Both Group A and Group B showed significantly better healing in terms of soft tissue and bone as compared to Group C. Conclusion: PRF shows better results in terms of soft tissue and bone healing as compared to PRP. The method of procuring PRF is easy as compared to that of procuring PRP.

Efficacy of bone regeneration using collagen microspheres as scaffold

Efficacy of bone regeneration using collagen microspheres as scaffold

Is Heparin Effective for the Controlled Delivery of High-Dose Bone Morphogenetic Protein-2?

Sustained release of bone morphogenetic protein (BMP)-2 by heparin-contained biomaterials is advantageous for bone tissue regeneration using low-dose BMP-2. However, its effect with high-dose BMP-2 is still unclear and should be clarified considering the clinical use of a high dose of BMP-2 in spine and oral surgery. This study aimed to evaluate the efficacy of a heparin-conjugated collagen sponge (HCS) with high-dose BMP-2 delivery by investigating in vivo initial osteogenic regulation and bone healing over 12 weeks in comparison with that of an absorbable collagen sponge (ACS). The in vitro BMP-2 release profile in the HCS exhibited a lower burst followed by a sustained release of BMP-2, whereas that of the ACS showed an initial burst phase only. As a result of a lower burst, the HCS-BMP group showed higher expression of bone-forming/resorbing markers and enhanced activation of osteoclasts than the ACS-BMP group within the scaffold of defect after 7 days, which is presumed to be because of retention of relatively higher amounts of BMP-2. However, the surrounding calvariae were less resorbed in the HCS-BMP group, compared with the aggressive resorptive response in the ACS-BMP group. Microcomputed tomography and histology revealed that HCS-BMP guided more effective bone regeneration of central defect over time inducing minor ossification at the defect exterior, whereas ACS-BMP exhibited excessive ossification at the defect exterior. These results showed that HCS-mediated BMP-2 delivery at a high dose has advantages over ACS, including less early resorption of surrounding bone tissue and higher efficacy in compact bone regeneration over a longer period, highlighting a clinical feasibility of this technology.

‘Pre-prosthetic use of poly(lactic-co-glycolic acid) membranes treated with oxygen plasma and TiO2 nanocomposite particles for guided bone regeneration processes’

ObjectivesGuided bone regeneration (GBR) processes are frequently necessary to achieve appropriate substrates before the restoration of edentulous areas. This study aimed to evaluate the bone regeneration reliability of a new poly-lactic-co-glycolic acid (PLGA) membrane after treatment with oxygen plasma (PO2) and titanium dioxide (TiO2) composite nanoparticles. MethodsCircumferential bone defects (diameter: 10mm; depth: 3mm) were created on the parietal bones of eight experimentation rabbits and were randomly covered with control membranes (Group 1: PLGA) or experimental membranes (Group 2: PLGA/PO2/TiO2). The animals were euthanized two months afterwards, and a morphologic study was then performed under microscope using ROI (region of interest) colour analysis. Percentage of new bone formation, length of mineralised bone formed in the grown defects, concentration of osteoclasts, and intensity of osteosynthetic activity were assessed. Comparisons among the groups and with the original bone tissue were made using the Kruskal–Wallis test. The level of significance was set in advance at a=0.05. ResultsThe experimental group recorded higher values for new bone formation, mineralised bone length, and osteoclast concentration; this group also registered the highest osteosynthetic activity. Bone layers in advanced formation stages and low proportions of immature tissue were observed in the study group. ConclusionsThe functionalised membranes showed the best efficacy for bone regeneration. Clinical significanceThe addition of TiO2 nanoparticles onto PLGA/PO2 membranes for GBR processes may be a promising technique to restore bone dimensions and anatomic contours as a prerequisite to well-supported and natural-appearing prosthetic rehabilitations.

In Vitro Osteogenic Potential of Green Fluorescent Protein Labelled Human Embryonic Stem Cell-Derived Osteoprogenitors.

Cellular therapy using stem cells in bone regeneration has gained increasing interest. Various studies suggest the clinical utility of osteoprogenitors-like mesenchymal stem cells in bone regeneration. However, limited availability of mesenchymal stem cells and conflicting evidence on their therapeutic efficacy limit their clinical application. Human embryonic stem cells (hESCs) are potentially an unlimited source of healthy and functional osteoprogenitors (OPs) that could be utilized for bone regenerative applications. However, limited ability to track hESC-derived progenies in vivo greatly hinders translational studies. Hence, in this study, we aimed to establish hESC-derived OPs (hESC-OPs) expressing green fluorescent protein (GFP) and to investigate their osteogenic differentiation potential in vitro. We fluorescently labelled H9-hESCs using a plasmid vector encoding GFP. The GFP-expressing hESCs were differentiated into hESC-OPs. The hESC-OPsGFP+ stably expressed high levels of GFP, CD73, CD90, and CD105. They possessed osteogenic differentiation potential in vitro as demonstrated by increased expression of COL1A1, RUNX2, OSTERIX, and OPG transcripts and mineralized nodules positive for Alizarin Red and immunocytochemical expression of osteocalcin, alkaline phosphatase, and collagen-I. In conclusion, we have demonstrated that fluorescently labelled hESC-OPs can maintain their GFP expression for the long term and their potential for osteogenic differentiation in vitro. In future, these fluorescently labelled hESC-OPs could be used for noninvasive assessment of bone regeneration, safety, and therapeutic efficacy.

Periodic Nanoneedle and Buffer Zones Constructed on a Titanium Surface Promote Osteogenic Differentiation and Bone Calcification In Vivo.

Rapid and effective bone mineralization at the bone/implant interface is required for successful orthopedic and dental implants. In this study, two periodic microscale functionalized zones on titanium (MZT) are created, namely, nanoneedle zones and buffer zones. The aim of this design is to provide spatially regulated topographical cues on titanium to enhance the efficacy of bone regeneration. This goal is achieved using a versatile and effective technique in which nanoneedle structures are hydrothermally constructed on the surface of titanium sheets, after which selective laser irradiation is used to construct buffer zones. The zonal structures of the MZT overcome the suppressive effect of the nanoneedle film on osteoblasts. Additionally, the MZT exhibits zone-selective apatite deposition and protein adsorption. The accelerated in vitro osteoblast differentiation and nodule deposition on the MZT are confirmed. Elemental analysis of the bone nodules formed by the osteoblasts growing on the titanium and MZT demonstrates they have different compositions. Histological and scanning electron microscope analysis of the bone formation on in vivo implants shows that this process is also enhanced by the MZT implant. The concept of constructing functionalized zones on titanium implant could facilitate future research on improving the design of orthopedic and dental implant surfaces.

BMPs in bone regeneration: Less is more effective, a paradigm-shift

Worldwide, the clinical application of BMP2 (bone morphogenetic protein 2) has helped an increasing number of patients achieve bone regeneration in a clinical area lacking simple solutions for difficult bone healing situations. In this review, the historical aspects and current critical clinical issues are summarized and positioned against new research findings on efficacy and function of BMP2. Knowledge concerning how the dose of this growth factor as well as its interaction with mechanical loading influences the efficacy of bone regeneration, might open possible future strategies in cases where bony bridging is unachievable so far. In conclusion, it is apparent that there is a substantial need for continued basic research to unravel the details of its function and the underlying signaling pathways involved, to make BMP2 even more relevant and safe in daily clinical use, even though this growth factor has been known for more than 125 years.

In situ hybridization of carbon nanotubes with bacterial cellulose for three-dimensional hybrid bioscaffolds

Carbon nanotubes (CNTs) have shown great potential in biomedical fields. However, in vivo applications of CNTs for regenerative medicine have been hampered by difficulties associated with the fabrication of three-dimensional (3D) scaffolds of CNTs due to CNTs' nano-scale nature. In this study, we devised a new method for biosynthesis of CNT-based 3D scaffold by in situ hybridizing CNTs with bacterial cellulose (BC), which has a structure ideal for tissue-engineering scaffolds. This was achieved simply by culturing Gluconacetobacter xylinus, BC-synthesizing bacteria, in medium containing CNTs. However, pristine CNTs aggregated in medium, which hampers homogeneous hybridization of CNTs with BC scaffolds, and the binding energy between hydrophobic pristine CNTs and hydrophilic BC was too small for the hybridization to occur. To overcome these problems, an amphiphilic comb-like polymer (APCLP) was adsorbed on CNTs. Unlike CNT-coated BC scaffolds (CNT-BC-Imm) formed by immersing 3D BC scaffolds in CNT solution, the APCLP-adsorbed CNT-BC hybrid scaffold (CNT-BC-Syn) showed homogeneously distributed CNTs throughout the 3D microporous structure of BC. Importantly, in contrast to CNT-BC-Imm scaffolds, CNT-BC-Syn scaffolds showed excellent osteoconductivity and osteoinductivity that led to high bone regeneration efficacy. This strategy may open a new avenue for development of 3D biofunctional scaffolds for regenerative medicine.

A high concentration of recombinant human bone morphogenetic protein‐2 induces low‐efficacy bone regeneration in sinus augmentation: a histomorphometric analysis in rabbits

The aim of the study was to elucidate the efficacy of bone regeneration at the early stage of healing in rabbit sinuses grafted with a biphasic calcium phosphate (BCP) carrier soaked in a high concentration of recombinant human bone morphogenetic protein-2 (rhBMP-2). Both maxillary sinuses of eight male rabbits were used. The sinus on one side (assigned randomly) was grafted with BCP loaded with rhBMP-2 (1.5mg/ml; test group) using a soaking method, while the other was grafted with saline-soaked BCP (control group). After a 2-week healing period, the sinuses were analyzed by micro-computed tomography and histomorphometry. The total augmented area and soft tissue space were significantly larger in the test group than in the control group, whereas the opposite was true for the area of residual material and newly formed bone. Most of the new bone in the test group was localized to the Schneiderian membrane (SM), while very little bone formation was observed in the window and center regions of the sinus. New bone was distributed evenly in the control group sinuses. Within the limitations of this study, it appeared that application of a high concentration of rhBMP-2 soaked onto a BCP carrier inhibited bone regeneration from the pristine bone and increased soft tissue swelling and inflammatory response at the early healing stage of sinus augmentation, although osteoinductive potential was found along the SM.

One step creation of multifunctional 3D architectured hydrogels inducing bone regeneration.

Structured hydrogels showing form stability and elastic properties individually tailorable on different length scales are accessible in a one-step process. They support cell adhesion and differentiation and display growing pore size during degradation. In vivo experiments demonstrate their efficacy in biomaterial-induced bone regeneration, not requiring addition of cells or growth factors.