Gene/Protein Disease Symptom Drug Enzyme Compound
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Hydroxyapatite (HA) and other calcium phosphates were synthesized on titanium plates by a solid-gas state reaction of sputtered CaO and vaporized P(2)O(5). The calcium phosphates formed were HA, beta-tricalcium phosphate (beta-TCP; Ca(3)(PO(4))(2)), beta-calcium pyrophosphate (beta-PYR; Ca(2)P(2)O(7)), and beta-calcium metaphosphate (beta-MET; Ca(2)(PO(3))(2)). Their formation depended on the ratio of the sputtered CaO and the reacting P(2)O(5). For a mole ratio of CaO/P(2)O(5)=4 (Ca/P=2), an HA film was synthesized. The surface roughness increased by over seven times after the solid-gas state reaction from Ra = 0.16+/-0.02 microm (for the CaO film) to Ra = 1.15+/-0.25 microm (for the reacted film). The synthesized HA film-coated titanium plates and control non-coated titanium plates were implanted in the femora of two dogs for a period of two, four and 12 weeks, and observed using a soft X-ray radiograph and histological sections. New bone formation was observed without any connective tissue at four weeks around the HA film, whereas over the 12 week experimental period, there was no new bone formation around the control and connective tissue was observed over all periods, reaching a thickness of more than 200 microm at 12 weeks.
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PMID:Preparation and osteocompatibility of hydroxyapatite coated on titanium from the reaction of sputtered CaO and vaporized P2O5. 1265 25

Our strategy entails investigating the influence of varied concentrations (0, 10, 100 and 1000ng/ml) of human recombinant bone morphogenetic protein-2 (rhBMP-2) on the osteogenic expression of canine osteoblasts, seeded onto poly-caprolactone 20% tricalcium phosphate (PCL-TCP) scaffolds in vitro. Biochemical assay revealed that groups with rhBMP-2 displayed an initial burst in cell growth that was not dose-dependent. However, after 13 days, cell growth declined to a value similar to control. Significantly less cell growth was observed for construct with 1000ng/ml of rhBMP-2 from 20 days onwards. Confocal microscopy confirmed viability of osteoblasts and at day 20, groups seeded with rhBMP-2 displayed heightened cell death as compared to control. Phase contrast and scanning electron microscopy revealed that osteoblasts heavily colonized surfaces, rods and pores of the PCL-TCP scaffolds. This was consistent for all groups. Finally, Von Kossa and osteocalcin assays demonstrated that cells from all groups maintained their osteogenic phenotype throughout the experiment. Calcification was observed as early as four days after stimulation for groups seeded with rhBMP-2. In conclusion, rhBMP-2 seems to enhance the differentiated function of canine osteoblasts in a non-dose dependent manner. This resulted in accelerated mineralization, followed by death of osteoblasts as they underwent terminal differentiation. Notably, PCL-TCP scaffolds seeded only with canine osteoblasts could sustain excellent osteogenic expression in vitro. Hence, the synergy of PCL with bioactive TCP and rhBMP-2 in a novel composite scaffold, could offer an exciting approach for bone regeneration.
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PMID:The effect of rhBMP-2 on canine osteoblasts seeded onto 3D bioactive polycaprolactone scaffolds. 1514 31

In this study, we first investigated the in vitro degradation properties of biodegradable, bioresorbable polycaprolactone-20% tricalcium phosphate (PCL-TCP) composites immersed in simulated body fluid (SBF) and phosphate buffered saline (PBS). Then, the release profiles of the growth factors present in platelet-rich plasma (PRP) loaded onto the composites incubated in SBF and PBS were compared. Composites immersed in both buffers showed water uptake of 13.7%+/-0.75 at day 1, followed by a constant uptake of 12.1%+/-0.3 until day 12. Henceforth the water uptake declined for SBF- and increased for PBS-soaked composites. The weight loss data did not reveal any trend. SBF- and PBS-soaked samples displayed 1-2% weight loss for 2 and 5 of the ten time points measured respectively. The original protein retention (PR) of the composites was 49.1%+/-1.50. After immersion in SBF and PBS for 4 weeks, the PR was augmented to 88.5%+/-1.40 and 69.1%+/-1.40 correspondingly. PRP after activation contained 164.7+/-24.8, 194+/-43 and 18.3+/-4.75 ng/ml of TGF-beta1, PDGF-BB and IGF-1. Microscopic analysis verified the attachment of PRP to the rods and pores of the composites. Interestingly, the buffers played an important role in determining the release profiles of TGF and PDGF. Firstly, PBS-soaked composites manifested a tri-phasic burst-like profile that was absent in SBF. Secondly, SBF-soaked composites experienced delayed release of the growth factors and total release was not achieved (64.4% for TGF and 60.5% for PDGF), whereas total release was realized for PBS-soaked composites. Lastly, release profiles from SBF-soaked composites were growth factor mediated in terms of their amounts and sizes. This was not observed for PBS-soaked composites. IGF-1, on the other hand, exhibited a progressive reduction in levels over the entire experimental period for both buffers. The mechanisms of release were theorized to be a combination of diffusion, degradation and bioactivity. Since SBF is analogous to our body fluids in terms of its ionic constituents, we expect the elution profiles derived from SBF-soaked samples to more accurately emulate the in vivo situation. In conclusion, this study has deemed PCL-TCP composites as suitable delivery systems for platelet-rich plasma.
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PMID:An in vitro evaluation of PCL-TCP composites as delivery systems for platelet-rich plasma. 1608 32

Understanding external factors that determine cellular phenotypic responses is of key interest in the field of biomaterials. Currently, material surface characteristics, protein adsorption and cellular phenotypic responses are all considered to be interrelated and ultimately determine the biocompatibility of materials. The exact nature of the relationship between these distinct, yet related, phenomena still remains to be elucidated. Through the use of a series of thermoresponsive N-isopropylacrylamide-based co-polymer films, we aimed to shed light on the relationship between surface hydrophobicity, protein adsorption and subsequent cellular response. Despite changes in co-polymer hydrophobicity mediated by altered ratios of constituent monomers, differential cellular response was only apparent in the presence of serum. Co-polymer films displayed alterations with respect to the amount of protein adsorbed on the surface, with individual serum proteins (albumin and fibronectin) displaying contrasting adsorption characteristics. Changes in protein adsorption corresponded to changes in cell adhesion, cytoskeletal organisation and cell morphology, as well as to changes in cell movement and intracellular signalling events. Examination of focal adhesion kinase (FAK), and extracellular signal-regulated kinase (ERK 1/2), important mediators of adhesion and growth factor-related signalling events, revealed a comparative reduction in phosphorylation of these signalling proteins in cells grown on co-polymers in comparison to those cultured on tissue culture polystyrene (TCP; used as a control surface). We also associated surface-mediated phenotypic alterations of cells grown on TCP and co-polymer films with particular changes in gene expression. These results indicate that cellular response to interaction with our series of co-polymer films is determined by the surface-adsorbed protein layer, which in turn is determined by the changing surface chemistry as the ratio of the co-monomers is altered.
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PMID:Surface-induced changes in protein adsorption and implications for cellular phenotypic responses to surface interaction. 1646 Jul 97

Porous scaffold biomaterials may offer a clinical alternative to bone grafts; however, scaffolds alone are typically insufficient to heal large bone defects. Numerous studies have demonstrated that osteoinductive growth factor or gene delivery significantly improves bone repair. However, given the important role of vascularization during bone regeneration, it may also be beneficial to incorporate factors that promote vascular ingrowth into constructs. In this study, a strategy combining structural polycaprolactone-20% tricalcium phosphate (PCL-TCP) composite scaffolds with platelet-rich plasma (PRP) was tested. Following bilateral implantation of constructs into 8 mm rat nonunion femoral defects, 3D vascular and bone ingrowth were quantified at 3 and 12 weeks using contrast-enhanced microcomputed tomography (micro-CT) imaging. At week 3, PRP-treated femurs displayed 70.3% higher vascular volume fraction than control femurs. Interestingly, bone volume fraction (BVF) was significantly higher for the empty scaffold group at the early time point. At 12 weeks, BVF measurements between the two groups were statistically equivalent. However, a greater proportion of PRP-treated femurs (83%) achieved bone union as compared to empty scaffold controls (33%). Consistent with this observation, biomechanical evaluation of functional integration also revealed a significantly higher torsional stiffness observed for PRP-treated defects compared to empty scaffolds. Ultimate torque at failure was not improved, however, perhaps due to the slow resorption profile of the scaffold material. Histological evaluation illustrated infiltration of vascularized connective tissue and bone in both groups. Given that bone ingrowth into untreated defects in this model is minimal, PCL-TCP scaffolds were clearly able to promote bone ingrowth but failed to consistently bridge the defect. The addition of PRP to PCL-TCP scaffolds accelerated early vascular ingrowth and improved longer-term functional integration. Taken together, the results of this study suggest that the use of PRP, alone or in combination with other bioactive components, may be an effective approach to augment the ability of porous biomaterial scaffolds to repair orthotopic defects.
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PMID:Combination of platelet-rich plasma with polycaprolactone-tricalcium phosphate scaffolds for segmental bone defect repair. 1790 42

Degradation studies of scaffolds are important in bone tissue engineering. Previously, novel poly(epsilon-caprolactone)-20% tricalcium phosphate (PCL-TCP) based scaffolds were developed and proven useful for bone regeneration. In this study in vitro degradation analyses were carried out with the PCL-TCP scaffolds immersed in standard culture medium for 24 weeks. In vivo degradation was performed with the scaffolds implanted in the abdomen of rats for the same period of time. Results demonstrated greater degradation of PCL-TCP scaffolds in vivo than in vitro. At 24 weeks, the increase of average porosity of the scaffolds in vivo was 29.2% compared to 2.65% in vitro. Gel permeation chromatography (GPC) analysis revealed a decrease of 29% and 20% respectively in the Mn and Mw values after 24 weeks in vitro. However, a significant decrease in Mn and Mw values (79.6% and 88.7% respectively) were recorded in vivo. The mechanical properties however, were relatively similar and closely match those of cancellous bone even at 24 weeks. The results showed that the scaffold can be used for dentoalveolar reconstruction and PCL-TCP scaffolds have shown to possess the potential to degrade within the desired time period of 5-6 months and favorable mechanical properties.
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PMID:The degradation profile of novel, bioresorbable PCL-TCP scaffolds: an in vitro and in vivo study. 1760 68

People suffering from pain due to osteoarthritic or rheumatoidal changes in the joints are still waiting for a better treatment. Although some studies have achieved success in repairing small cartilage defects, there is no widely accepted method for complete repair of osteochondral defects. Also joint replacements have not yet succeeded in replacing of natural cartilage without complications. Therefore, there is room for a new medical approach, which outperforms currently used methods. The aim of this study is to show potential of using a tissue engineering approach for regeneration of osteochondral defects. The critical review of currently used methods for treatment of osteochondral defects is also provided. In this study, two kinds of hybrid scaffolds developed in Hutmacher's group have been analysed. The first biphasic scaffold consists of fibrin and PCL. The fibrin serves as a cartilage phase while the porous PCL scaffold acts as the subchondral phase. The second system comprises of PCL and PCL-TCP. The scaffolds were fabricated via fused deposition modeling which is a rapid prototyping system. Bone marrow-derived mesenchymal cells were isolated from New Zealand White rabbits, cultured in vitro and seeded into the scaffolds. Bone regenerations of the subchondral phases were quantified via micro CT analysis and the results demonstrated the potential of the porous PCL and PCL-TCP scaffolds in promoting bone healing. Fibrin was found to be lacking in this aspect as it degrades rapidly. On the other hand, the porous PCL scaffold degrades slowly hence it provides an effective mechanical support. This study shows that in the field of cartilage repair or replacement, tissue engineering may have big impact in the future. In vivo bone and cartilage engineering via combining a novel composite, biphasic scaffold technology with a MSC has been shown a high potential in the knee defect regeneration in the animal models. However, the clinical application of tissue engineering requires the future research work due to several problems, such as scaffold design, cellular delivery and implantation strategies.
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PMID:Repair and regeneration of osteochondral defects in the articular joints. 1793 65

The degradation of polycaprolactone-20% tricalcium phosphate (PCL-TCP) scaffolds was customized for dentoalveolar augmentation applications, where 5-6 months period is optimal. The scaffolds were treated with either 3M sodium hydroxide (NaOH) or 0.1% lipase solution for a total of 108 h. A greater degree of degradation and reduction in the physical properties of the scaffolds was observed in the lipase treated when compared with NaOH-treated scaffolds. After 108 h, increases in weight loss and average porosity of the scaffolds in the lipase-treated group measured 90.6% and 22.9%, respectively, when compared with 52.8% and 11.8% in the NaOH-treated group. The mechanical testing results revealed a similar trend, with a complete loss of compressive strength and modulus measured as early as 60 h in the lipase-treated group. The honeycomblike architecture was well preserved throughout the experiment only for the NaOH-treated scaffolds in addition to a favorable surface roughness ideal for bone-regeneration applications. In conclusion, pretreatment with NaOH demonstrates a simple approach for tailoring the physical properties and degradation rate of PCL-TCP scaffolds for the potential use as biomaterials targeted for dentoalveolar bone-regeneration procedures.
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PMID:Customizing the degradation and load-bearing profile of 3D polycaprolactone-tricalcium phosphate scaffolds under enzymatic and hydrolytic conditions. 1854 98

In this work, three-dimensional porous composite scaffolds, based on poly(epsilon-caprolactone) (PCL), were fabricated through the combination of a filament winding technique and a phase inversion/salt leaching process. Sodium chloride crystals were used as the porogen agent, and poly(lactic acid) (PLA) fibers and calcium phosphates as reinforcement. The aim of the current work is to assess the effective synergistic role of bioactive particles (i.e. alpha-tricalcium phosphates (alpha-TCP)) and PLA fibers on the morphology and mechanical response of the final scaffold. Morphological investigations performed on fiber-reinforced composite scaffolds with different PCL/alpha-TCP volume ratios (0%, 13%, 20% and 26%) show a high porosity degree (ca. 80%), pore interconnection and a homogeneous distribution of pores within the scaffold. More specifically, a bimodal pore size distribution was observed. This comprised microporosity (pores with radii ranging from 0.1 to 10 microm, which were strictly related to solvent extraction) and macroporosity (pores with radii from 10 to 300 microm, which were ascribable to the leaching of porogen elements). Static compressive tests showed that the effect of alpha-TCP on the mechanical response was to increase the elastic modulus up to a maximum value of 2.21+/-0.24 MPa, depending on the concentration of alpha-TCP added. This effect may be explained through the interaction of calcium-deficient hydroxyapatite crystals, formed as a consequence of a hydrolysis reaction of alpha-TCP, and the fiber-reinforced polymer matrix. The correct balance between chemical composition and spatial organization of reinforcement systems allows the attainment of an ideal compromise between mechanical response and bioactive potential, facilitating the development of composite scaffolds for bone tissue engineering applications.
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PMID:The synergic effect of polylactide fiber and calcium phosphate particle reinforcement in poly epsilon-caprolactone-based composite scaffolds. 1857 87

Pretreatment of polycaprolactone-20% tricalcium phosphate (PCL-TCP) scaffolds under alkaline conditions can be utilized to alter surface characteristics for enhanced early bone formation. PCL-TCP scaffolds were treated with sodium hydroxide (NaOH) at various time intervals (group A: untreated, group B: 3M NaOH for 48 h, and group C: 3M NaOH for 96 h). In vitro results showed a greater degree of physical changes in the NaOH-treated scaffolds (B and C) than the untreated group (A). Clearly, the NaOH-treated scaffolds showed an increased surface roughness than the untreated ones. A significantly large number of "channel-like" pits and greater average pit sizes were detected in groups B (14.51 +/- 10.9 microm) and C (20.27 +/- 14.3 microm); and absent in group A. In addition, treated scaffolds had a significant reduction of the water contact angle (40.9-58.2%). Favorably, the pore dimensions and scaffold rod thickness remained unchanged throughout the experiment. When implanted in the calvaria of rabbits, NaOH-treated scaffolds reported greater early matrix deposition and bone formation from scanning electron images and Micro-computed tomography analyses. In conclusion, pretreatment of PCL-TCP scaffolds with NaOH increases the wettability and surface area for initial matrix deposition and early bone ingrowth.
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PMID:Surface modification of PCL-TCP scaffolds improve interfacial mechanical interlock and enhance early bone formation: an in vitro and in vivo characterization. 1918 86


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