Molecular and mechanical property changes during aging of bone cement in vitro and in vivo

The changes in mechanical properties and free radical concentration of curing Simplex P Radiopaque Bone Cement in vivo and in vitro conditions were studied. Samples were prepared so that each in vivo sample that cured and aged in the canine femoral intramedullary cavities had an in vitro counterpart that was cured and aged in a constant-temperature saline bath at 37 degrees C. An electron paramagnetic resonance (EPR) spectrometer was used to measure the growth and decay (curing) of polymerization radicals. The results of EPR measurements showed that the curing (disappearance of free radicals) of in vivo samples takes a much longer time (more than 4 weeks) than in vitro curing (less than 2 weeks). The mechanical tests indicate that, whether aged in vivo or in vitro, the strength increased rapidly for the first 1-2 weeks and then slight increases were seen for up to 6 months.     

Material characterization and in vivo behavior of silicon substituted alpha-tricalcium phosphate cement

The possibility and biological effects of substituting silicon in alpha-tricalcium phosphate (alpha-TCP) by way of solid-state reaction have been evaluated. alpha-TCP powders with varying substitution amounts (1 and 5 mol % Ca2SiO4) were synthesized by reacting mixtures of CaCO3, Ca2P2O7, and SiO2, at a rate of 4 degrees C(min)(-1) to 1100 degrees C, left to dwell for 2 h and then heated to 1325 degrees C at 4 degrees C(min)(-1) and left to dwell for a period of 4 h. The powders were then rapidly quenched in air. Si incorporation could be verified by X-ray diffraction analysis, indicating an increase of the lattice volume with increasing Si content from 4284.1(8) to 4334(1) A3 for pure alpha-TCP and alpha-Si5%TCP, respectively. The hydrolysis of milled alpha-SiTCP powders was monitored by isothermal calorimetry, and the compressive strength of set cements was tested. The results showed changes in speed and amount of heat released during reactivity tests and a decrease in mechanical strength (60, 50, and 5 MPa) with increasing Si content. In vitro bioactivity of the set cements after soaking in simulated body fluid for 4 weeks was also tested. The formation of a bonelike apatite layer on the surface of the set cements could be observed and was thickest for 1%Si (20 microm). These results were in good agreement with the in vivo studies performed, which showed strong evidence that the cement containing 1% silicon doped alpha-TCP enhanced mesenchymal cell differentiation and increased osteoblast activity compared with alpha-TCP.     

Effect of a plasmaelectrolytic coating on the strength retention of in vivo and in vitro degraded magnesium implants

The strength decrease in magnesium implants was studied in vitro and in vivo, with and without a protective plasmaelectrolytic coating. In vivo, degradation was examined by implanting rectangular plates on top of the nasal bone of miniature pigs. The presence of gas pockets in the soft tissue surrounding the implants was evaluated with intermediate X-rays and computed X-ray tomography scans before euthanasia. After 12 and 24 weeks of in vivo degradation, the large rectangular plates were removed and mechanically tested in three-point bending. In vitro, identical plates were immersed in simulated body fluid for 4, 8 and 12 weeks. In vitro and in vivo results showed that onset of gas release can be delayed by the plasmaelectrolytic coating. Mass loss and strength retention during in vivo degradation is about four times slower than during in vitro degradation for the chosen test conditions. Despite the slow degradation of the investigated WE43 alloy, the occurrence of gas pockets could not be completely avoided. Nevertheless, uniformity of degradation and reliable strength retention make this alloy a prime candidate for the use of magnesium in cranio-maxillofacial surgery.     

Tissue-engineered repair of osteochondral defects: effects of the age of donor cells and host tissue

Transplantation of a tissue-engineered construct containing cells of a chondrocytic phenotype into an osteochondral defect provides a biological solution to this type of injury. Among the factors that affect cell proliferation and phenotypic expression, age is one that has not been well characterized. In this study adult and aged male donor cells, derived from perichondrium, were cultured and adsorbed into a polylactic acid (PLA) scaffold and transplanted into osteochondral defects created in adult (8- to 10-month-old) and aged (4- to 5-year-old) female rabbits. Three groups were investigated: (1) adult cells transplanted into aged defects, (2) aged cells transplanted into aged defects, and (3) aged cells transplanted into adult defects. In vitro characterization of adult and aged cells and in vivo assessment of osteochondral repair tissue at 12 weeks posttransplantation were carried out. The in vitro studies demonstrated that the proliferation rate of aged cells was less than that of mature cells during the earliest stage of culture. Also, the chondrocytic phenotype was reduced in aged cells compared with mature cells. The in vivo results showed that donor (SRY-positive) cell survival differed among the three groups: survival of adult cells into aged defect > survival of aged cells into aged defect > survival of aged cells into adult defect. The biological acceptability of the repair, defined as smooth firm cartilaginous tissue filling the defect, was < 25% of the operated specimens in each of the three groups. This repair tissue contained only 20-25% of the amounts of type II collagen and glycosaminoglycans found in normal articular cartilage. These data suggest that the outcome of tissue-engineered repair of osteochondral defects is affected by both the age of donor cells and the age of the host.     

An in vitro investigation of plasma sprayed hydroxyapatite (HA) coatings produced with flame-spheroidized feedstock.

The in vitro behaviour and characteristics of plasma sprayed hydroxyapatite (HA) coatings using flame-spheroidized HA feedstock powder on titanium alloy (Ti-6Al-4V) substrates were investigated in a simulated physiological environment as an attempt to reflect the actual incubational condition of an implant in a human body system. As-sprayed and heat-treated HA coatings were immersed in a simulated body fluid with ionic concentrations comparable to that of human blood plasma for time intervals 2, 4, 6, 8 and 10 weeks. Rapid dissolution of calcium phosphate was found to occur within the first 4 weeks, and after the 5th week a retarding rate of 4.1 mM week(-1) was observed where precipitation, nucleation, and, growth of a carbonate-containing, poorly crystallized or amorphous calcium phosphate layer on the as-sprayed coatings were noted. The heat-treated coatings showed minimal or no precipitation on the surface except for the presence of calcite minerals that is due to carbonation effect. Complete dissolution of other calcium phosphate phases such as tetracalcium phosphate, tricalcium phosphate and calcium oxide was also noted after 2 weeks of immersion due to higher ionic solubility relative to HA. A declining trend in respective microhardness and elastic modulus of the as-sprayed HA coatings from 207.06 +/- 3.2 H(k300) to 131.8 +/- 5.2 H(k300) and from 31.37 +/- 1.4 to 19.81 +/- 1.6 GPa was observed after 10 weeks of immersion. Tensile bond strength of both types of coatings showed similar declining trend, with an average dip from 24.5 +/- 2.4 to 7.9 +/- 2.6 MPa. Nevertheless. the heat-treated samples showed rather reasonable mechanical stability and structural integrity of 26.7 +/-1.4 GPa in elastic modulus after soaking.     

Comparison of the biomechanics and histology of two soft-tissue fixators composed of bioabsorbable copolymers

The purpose of this study was to assess the dynamic in vitro and in vivo characteristics of two different bioabsorbable copolymer soft-tissue fixation devices and to determine their efficacy in reattaching soft tissue to bone. Suretac fixators (Smith & Nephew/Acufex MicroSurgical Inc., Northwood, MA), made of polyglyconate (2:1 glycolic acid:trimethylene carbonate), and Pop Rivets (Arthrotek, Warsaw, IN), made of LactoSorb (82% poly L-lactic acid, 18% polyglycolic acid), were anchored into synthetic bone, and their pull-out strengths were evaluated. The devices were also evaluated with the use of an in vivo goat model in which the medial collateral ligament (MCL) was elevated from the tibia and directly reattached. In the in vitro biomechanical study, the Suretac fixators had negligible strength remaining by four weeks, whereas the Pop Rivets retained 50% of their strength at 4 weeks, 20% at 8 weeks, and negligible strength at 12 weeks. The in vivo strength of MCL repairs affected by each implant was not statistically different at any of the time points. Histologically, both implants were absorbed by 52 weeks, and there was no appreciable adverse tissue response. In conclusion, both copolymer fixators were found to be biocompatible. The Pop Rivet fixators demonstrated in vivo performance comparable to the Suretac fixators, although the Pop Rivets retained strength longer in vitro. Our results suggest that both devices provide adequate strength of fixation before degrading to allow the healing soft tissues to reach or surpass their native strength.     

A comparison of in vitro and in vivo degradation of two CPC strain gauge coatings

Calcium phosphate ceramic (CPC) coated strain gauges have been used to measure bone strain in animal models for up to 16 weeks and are being developed to collect measurements in patients for periods of 1 year or more. A published surface roughening and heat treating procedure produced improved dry strength and in vivo stability of CPC-gauge interfaces after 16 weeks. The long term bond strength of two CPC-gauge interfaces prepared using the roughening and heat treating process were evaluated after up to 1 year in vitro and in vivo using a lap shear test. The feasibility of using an in vitro test to predict long term in vivo interface changes was established. A blended tricalcium phosphate + hydroxyapatite had a CPC-gauge interface strength which decreased from 6.07 +/- 2.64 MPa at 16 weeks to 4.71 +/- 1.840 MPa after 1 year in Hanks Balanced Salts (HBS). The same coating had a strength that decreased from 8.51 +/- 2.63 MPa at 16 weeks to 5.35 +/- 1 MPa after 1 year in vivo. A soluble calcium enhanced hydroxyapatite had an interface strength of 4.83 +/- 1.106 MPa after 16 weeks and 4.51+/- 1.100 MPa after 1 year in HBS. The same coating had an interface strength of 8.34 +/- 2.40 MPa after 16 weeks and 5.20 +/- 2.00 MPa after 1 year in vivo. Although interface strengths decreased slightly with time in vivo, after 1 year they were in the same strength range as published CPC-bone interface strengths of 4.8 +/- 2.4 MPa. Comparison of in vitro with in vivo results indicated that in vitro results were a good predictor of strength change in the blended CPC coating, but a poorer predictor of strength changes in the soluble calcium-enhanced coating.     

Mechanical properties of native and reconstituted rat tail tendon collagen upon maturation in vitro

Native and reconstituted rat tail tendon collagen were tested mechanically after in vitro maturation by incubation. The mechanical strength of the native tendons increased upon incubation and attained maximum strength values similar to those of tendons matured and aged in vivo. This finding indicates that the same stabilizing process occurs both in vivo and in vitro. However, the mechanical strength values similar to those of tendons matured and aged in vivo. This finding indicates that the same stabilizing process occurs both in vivo and in vitro. However, the mechanical strength increased at an initial higher rate in vitro than in vivo. The mechanical strength of fibrils reconstituted from purified tail tendon collagen increased during incubation in air as previously reported for fibrils prepared from skin collagen. Fibrils prepared from tail tendon and skin collagen shared common mechanical and thermal stability characteristics upon the incubation. However, distinct qualitative mechanical characteristics for fibrils of the two collagens were found. These characteristics showed a resemblance to those of the respective source tissues. The results indicate that the same process is responsible for the gain in mechanical strength of native tissues and reconstituted collagen fibrils. Thus, reconstituted collagen fibrils seem a useful model for studying mechanical stability changes during maturation of collagen.     

In vitro and in vivo studies on bioabsorbable ultra-high-strength poly(L-lactide) rods.

Ultra-high-strength poly(L-lactide) (PLLA) rods were fabricated using a drawing technique. Rods with a diameter of 3.2 mm and a draw ratio of 2.5:1 showed initial bending strength and modulus values of 240 MPa and 13 GPa, respectively. The purpose of this study was to investigate the in vitro and in vivo degradation of PLLA rods with a draw ratio of 2.5:1. The greater the rod diameter, the longer the bending strength was maintained in phosphate buffered saline at 37 degrees C. The bending strength retention of rods (diam. 3.2 mm) implanted in the subcutis of rabbits was almost equal to that of rods in the in vitro study, while those rods implanted in the medullary cavity of rabbit femora showed a slightly lower bending strength retention. Molecular weight was reduced to the greatest extent in the medullary cavity, followed by in the subcutis and in vitro. The weight of PLLA rods in the medullary cavity was reduced by 22% at 52 weeks and by 70% at 78 weeks after implantation. Histologically, no inflammatory or foreign body reaction was observed in the medullary cavity for 52 weeks. The drawn PLLA rods maintained a bending strength exceeding that of human cortical bone in the medullary canal for a period of 8 weeks, suggesting that the drawn PLLA rods may be useful in the repair of fractured human bones.     

Correlations between the in vitro and in vivo bioactivity of the Ti/HA composites fabricated by a powder metallurgy method

Ti/HA composites were successfully prepared by a powder metallurgy method and the effect of phase composition on the in vitro and in vivo bioactivity of the Ti/HA composites was investigated in the present study. The correlations between the in vitro and in vivo biological behaviors were highlighted. The results showed that the in vitro and in vivo bioactivity of the Ti/HA composites was dependent on their phase composition. The in vitro bioactivity of the Ti/HA composites was evaluated in simulated body fluid with ion concentrations similar to those of human plasma. After immersion in the simulated body fluid for a certain time, apatite precipitations formed on the surface of the composites with an initial titanium content of 50 and 70 wt.%, and no apatite was found on the surface of the composite with 30% titanium. Ti(2)O was responsible for the apatite formation on the surfaces of the composites. For in vivo analysis, Ti/HA cylinders were implanted in the metaphases of the rabbit femur. At the early stage of implantation, the new bone formed on the surface of the composite with 30% titanium was much less than that on the surfaces of the composites with 50% and 70% titanium. All the Ti/HA composites formed a chemical bone-bonding interface with the host bone by 6 months after implantation. The Ti/HA composites formed the bone-bonding interface with the surrounding bone through an apatite layer. The results in the present study suggested that the in vivo results agreed well with the in vitro results.     

Bioactive titanium: effect of sodium removal on the bone-bonding ability of bioactive titanium prepared by alkali and heat treatment

As reported previously, bioactive titanium is prepared by simple alkali and heat treatment, and can bond to living bone directly. The purpose of this study was to accelerate the bioactivity of bioactive titanium in vivo. In in vitro study, sodium removal by hot water immersion enhanced the apatite-forming ability of bioactive titanium in simulated body fluid dramatically. The specific anatase structure of titania gel was effective for apatite formation in vitro. In the current study, we investigated the in vivo effect of sodium removal on the bone-bonding strength of bioactive titanium. Sodium-free bioactive titanium plates were prepared by immersion in an aqueous solution of 5 M NaOH at 60 degrees C for 24 h, followed by immersion in distilled water at 40 degrees C for 48 h before heating them at 600 degrees C for 1 h. Three kinds of titanium plates were inserted into rabbit tibiae, including untreated cp-Ti, conventional alkali- and heat-treated Ti, and sodium-free alkali- and heat-treated Ti. In vivo bioactive performance was examined mechanically and histologically after 4, 8, 16, and 24 weeks. Sodium removal enhanced the bone-bonding strength of bioactive titanium at 4 and 8 weeks postoperatively; however, its bone-bonding strength was inferior to that of conventional alkali- and heat-treated titanium at 16 and 24 weeks. Histological examinations after the detaching test revealed breakage of the treated layer in the sodium-free alkali- and heat-treated titanium group. In conclusion, sodium removal accelerated the in vivo bioactivity of bioactive titanium and achieved faster bone-bonding because of its anatase surface structure, but the loss of the surface's graded structure due to the complete removal of sodium decreased the adhesive strength of the treated layer to the titanium substrate. Further investigations are required to determine the optimum conditions for preparation of bioactive titanium.     

Biocompatibility and state fatigue behavior of glassy carbon.

1. The normal stages of bone modeling and remodeling occur following the implantation of carbon plugs. 2. Glassy carbon bars aged in vivo for five months did not undergo statistically significant weakening. 3. Glassy carbon does undergo static fatigue when aged in a simulated biological environment. However, the conditions necessary to cause this failure are extreme. 4. Minimal tissue response was seen to the presence of the carbon.     

Retention of in vitro and in vivo BMP-2 bioactivities in sustained delivery vehicles for bone tissue engineering

In this study, we investigated the in vitro and in vivo biological activities of bone morphogenetic protein 2 (BMP-2) released from four sustained delivery vehicles for bone regeneration. BMP-2 was incorporated into (1) a gelatin hydrogel, (2) poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in a gelatin hydrogel, (3) microspheres embedded in a poly(propylene fumarate) (PPF) scaffold and (4) microspheres embedded in a PPF scaffold surrounded by a gelatin hydrogel. A fraction of the incorporated BMP-2 was radiolabeled with (125)I to determine its in vitro and in vivo release profiles. The release and bioactivity of BMP-2 were tested weekly over a period of 12 weeks in preosteoblast W20-17 cell line culture and in a rat subcutaneous implantation model. Outcome parameters for in vitro and in vivo bioactivities of the released BMP-2 were alkaline phosphatase (AP) induction and bone formation, respectively. The four implant types showed different in vitro release profiles over the 12-week period, which changed significantly upon implantation. The AP induction by BMP-2 released from gelatin implants showed a loss in bioactivity after 6 weeks in culture, while the BMP-2 released from the other implants continued to show bioactivity over the full 12-week period. Micro-CT and histological analysis of the delivery vehicles after 6 weeks of implantation showed significantly more bone in the microsphere/PPF scaffold composites (Implant 3, p<0.02). After 12 weeks, the amount of newly formed bone in the microsphere/PPF scaffolds remained significantly higher than that in the gelatin and microsphere/gelatin hydrogels (p<0.001), however, there was no statistical difference compared to the microsphere/PPF/gelatin composite. Overall, the results from this study show that BMP-2 could be incorporated into various bone tissue engineering composites for sustained release over a prolonged period of time with retention of bioactivity.     

In vitro cellular response and in vivo primary osteointegration of electrochemically modified titanium

Anodic spark deposition (ASD) is an attractive technique for improving the implant–bone interface that can be applied to titanium and titanium alloys. This technique produces a surface with microporous morphology and an oxide layer enriched with calcium and phosphorus. The aim of the present study was to investigate the biological response in vitro using primary human osteoblasts as a cellular model and the osteogenic primary response in vivo within a short experimental time frame (2 and 4 weeks) in an animal model (rabbit). Responses were assessed by comparing the new electrochemical biomimetic treatments to an acid-etching treatment as control. The in vitro biological response was characterized by cell morphology, adhesion, proliferation activity and cell metabolic activity. A complete assessment of osteogenic activity in vivo was achieved by estimating static and dynamic histomorphometric parameters at several time points within the considered time frame. The in vitro study showed enhanced osteoblast adhesion and higher metabolic activity for the ASD-treated surfaces during the first days after seeding compared to the control titanium. For the ASD surfaces, the histomorphometry indicated a higher mineral apposition rate within 2 weeks and a more extended bone activation within the first week after surgery, leading to more extensive bone–implant contact after 2 weeks. In conclusion, the ASD surface treatments enhanced the biological response in vitro, promoting an early osteoblast adhesion, and the osteointegrative properties in vivo, accelerating the primary osteogenic response.     

Fibrin-based model for cartilage regeneration: tissue maturation from in vitro to in vivo

One of the crucial points for a successful tissue-engineering approach for cartilage repair is represented by the level of in vitro maturation of the engineered tissue before implantation. The purpose of this work was to evaluate the effect of the level of in vitro maturation of engineered cartilaginous samples on the tissue quality after in vivo implantation. Samples were obtained from isolated swine articular chondrocytes embedded in fibrin glue. The cell-fibrin composites were either cultured in vitro or directly implanted in vivo for 1, 5, and 9 weeks. Other experimental samples were precultured for either 1 or 5 weeks in vitro and then implanted in vivo for 4 additional weeks. All the samples were analyzed by histology, immunohistochemistry, biochemistry, and gene expression. The results strongly suggest that the in vivo culture in this model promoted a better tissue maturation than that obtained in the in vitro condition, and that 1 week in vitro preculture resulted in the primary structuring of the engineered composites and their subsequent maturation in vivo, without affecting the cell viability and activity, while a prolonged in vitro preculture caused a cell and matrix degeneration that could not be rescued in vivo.     

A comparative study between in vivo bone ingrowth and in vitro apatite formation on Na2O-CaO-SiO2 glasses

This study compared in vivo bioactivity with the in vitro apatite-forming ability of biomaterials. Granules of five kinds of P(2)O(5)-free Na(2)O-CaO-SiO(2) glasses, showing different apatite-forming ability in simulated body fluid (SBF), were implanted into a defect on the femoral condyle of rabbits. Bone ingrowth was evaluated using scanning electron microscopy among five kinds of glasses at 1, 2, 3, 6, and 12 weeks. Quantitative analysis was performed measuring the depth of new bone ingrowth from the periphery. In addition, the total areas of newly formed bone among glass particles were examined at 3 and 6 weeks using confocal laser scanning microscopy (CLSM) after weekly administration of fluorescent calcein. The depth of bone ingrowth among glass particles increased in proportion to their apatite-forming ability in vitro. The CLSM study showed a correlation between the quantities of labeled newly formed bone and in vitro apatite-forming ability. In the P(2)O(5)-free Na(2)O-CaO-SiO(2) glasses, the periods within 3-6 days for inducing apatite in SBF considered a necessary condition to convey bioactivity in vivo, and in vivo evaluations at 2-3 weeks is important to determine this. The in vivo bioactivity was precisely reproduced by apatite-forming ability in SBF. Therefore, evaluating apatite formation in SBF is a good screening test for the in vivo bioactivity of materials, resulting in reduction of the need for animal sacrifices and savings in experimental time.     

Bone bonding bioactivity of Ti metal and Ti-Zr-Nb-Ta alloys with Ca ions incorporated on their surfaces by simple chemical and heat treatments

Ti15Zr4Nb4Ta and Ti29Nb13Ta4.6Zr, which do not contain the potentially cytotoxic elements V and Al, represent a new generation of alloys with improved corrosion resistance, mechanical properties, and cytocompatibility. Recently it has become possible for the apatite forming ability of these alloys to be ascertained by treatment with alkali, CaCl2, heat, and water (ACaHW). In order to confirm the actual in vivo bioactivity of commercially pure titanium (cp-Ti) and these alloys after subjecting them to ACaHW treatment at different temperatures, the bone bonding strength of implants made from these materials was evaluated. The failure load between implant and bone was measured for treated and untreated plates at 4, 8, 16, and 26 weeks after implantation in rabbit tibia. The untreated implants showed almost no bonding, whereas all treated implants showed successful bonding by 4 weeks, and the failure load subsequently increased with time. This suggests that a simple and economical ACaHW treatment could successfully be used to impart bone bonding bioactivity to Ti metal and Ti-Zr-Nb-Ta alloys in vivo. In particular, implants heat treated at 700 °C exhibited significantly greater bone bonding strength, as well as augmented in vitro apatite formation, in comparison with those treated at 600 °C. Thus, with this improved bioactive treatment process these advantageous Ti-Zr-Nb-Ta alloys can serve as useful candidates for orthopedic devices.     

生物钟节律紊乱影响糖尿病小鼠糖代谢及胰岛素分泌的实验研究

目的 探究生物钟节律紊乱对糖尿病肥胖小鼠（ob/ob）糖代谢及胰岛素分泌的影响。方法 选取同体重的6~8周龄C57BL/6及ob/ob小鼠各12只,随机分为对照组（C57组）、糖尿病组（OB组）、对照组+生物钟节律干扰组（C57+CSD组）、糖尿病组+生物钟节律干扰组（OB+CSD组）,每组6只。C57+CSD组和OB+CSD组小鼠分别置于高台水环境下干扰其生物钟节律。C57组和OB组小鼠分别置于标准饲养笼中,其生物钟节律不受干扰,动物体重每天监测1次。4周后行小鼠体内腹腔注射葡萄糖耐量实验（IPGTT,2 g/kg）,分离实验小鼠胰岛行体外葡萄糖刺激胰岛素分泌实验（GSIS）。结果 C57、C57+CSD和OB组体重分别增长22.92%、0.42%和26.16%,而OB+CSD组下降0.17%。空腹血糖测定显示:OB组与OB+CSD组血糖值水平高于C57组和C57+CSD组（P＜0.05）;IPGTT实验显示:OB组小鼠血糖峰值明显后移,且在15、30、60、90 min的血糖均高于C57组（P＜0.05）;C57+CSD组小鼠各时间点血糖均高于C57组（P＜0.05）,OB+CSD组小鼠于120 min的血糖高于OB组（P＜0.05）;体内、体外胰岛素测定显示:C57胰岛素分泌低于OB组（P＜0.05）,C57+CSD组胰岛素分泌低于C57组（P＜0.05）,OB+CSD组血清及体外胰岛胰岛素分泌低于OB组（P＜0.05）。结论 生物钟节律是维护糖代谢稳态的重要环节,其紊乱可能导致正常及糖尿病小鼠胰岛素分泌的减低。     

In vitro and in vivo behaviour of biodegradable and injectable PLA/PGA copolymers related to different matrices

This study comparatively investigates the in vitro and in vivo behavior of injectable polymeric materials for the treatment of bone defects. The tested materials were three injectable and biodegradable PLA/PGA 50/50 copolymers dispersed in different matrices: Fisograft-gel (GEL) was dispersed in an aqueous matrix of poly-ethyl-glycole (PEG); Slurry2 (SL2) was dispersed in an aqueous matrix of PEG and dextran; and Slurry6 (SL6) was dispersed in a 3% agarose matrix. The biological characterization of these materials was studied by in vitro and in vivo tests: the in vitro test assessed the cellular response in terms of viability, differentiation and synthetic activity, while the in vivo test evaluated the healing capacity of bone defects treated with these biomaterials. GEL and SL2 induced a similar response for viability and differentiation of MG63 osteoblast-like cells after a 7-day culture, while SL6 caused a higher production of both interleukin-6 and type I collagen. Since the results showed that the materials were biocompatible and not cytotoxic in vitro, the in vivo study was carried out: materials were implanted, under general anesthesia, in critical size defects of rabbit femoral condyles; after 4 and 12 weeks, the healing rates and the quality of the regenerated bone were histomorphometrically calculated. The SL2-treated defects healed better at 12 weeks with a more similar microarchitecture of the newly formed bone to normal bone in comparison with other materials, as demonstrated by bone volume fraction and trabecular thickness values.     

Development of water-insoluble chitosan patch scaffold to repair traumatic tympanic membrane perforations

Perforated tympanic membranes (TM) and otitis media can be managed with a paper patch or tympanoplasty. However, a paper patch is not biocompatible and tympanoplasty requires complex aseptic surgical procedures. A novel biocompatible patch with a water-insoluble chitosan as the main component was prepared. Optimal mechanical characteristics of a water-insoluble chitosan patch scaffold (CPS) was approximately 40 microm in thickness, 7 MPa in tensile strength, and 107% in percent elongation, even though the characteristics varied significantly depending on the concentrations of chitosan and glycerol. SEM of the CPSs showed a very smooth surface as compared with that of the paper patches. These CPSs showed no cytotoxicity and had a stimulating effect on the proliferation of TM cells in in vitro study. In in vivo study, 4 (21.1%) and 17 (89.5%) TMs out of 19 adult rats with CPSs showed no perforations at 1 and 2 weeks, respectively. However, left control TMs showed healing of 0 (0%) at 1 week and 18 (94.7%) at 2 weeks. TEM findings of regenerated eardrums using CPSs showed thinner, smoother, and more compact tissues than spontaneously healed eardrums. A CPS was more effective than spontaneous healing to repair traumatic TM perforations.