Elastomeric enriched biodegradable polyurethane sponges for critical bone defects: a successful case study reducing donor site morbidity.

Bone substitutes have been a critical issue as the natural source can seldom provide enough bone to support full healing. No bone substitute complies with all necessary functions and characteristics that an autograft does. Polyurethane sponges have been used as a surgical alternative to cancellous bone grafts for critical bone defect donor sites. Critical bone defects were created on the tibial tuberosity and iliac crest using an ovine model. In group I (control-untreated), no bone regeneration was observed in any animal. In group II (defects left empty but covered with a microporous polymeric membrane), the new bone bridged the top ends in all animals. In groups III and IV, bone defects were implanted with polyurethane scaffolds modified with biologically active compounds, and bone regeneration was more efficient than in group II. In groups III and IV there were higher values of bone regeneration specific parameters used for evaluation (P < 0.05) although the comparison between these groups was not possible. The results obtained in this study suggest that biodegradable polyurethane substitutes modified with biologically active substances may offer an alternative to bone graft, reducing donor site morbidity associated with autogenous cancellous bone harvesting.

Biodegradable poly(ester urethane) urea scaffolds for tissue engineering: Interaction with osteoblast-like MG-63 cells.

Porous three-dimensional scaffolds with potential for application as cancellous bone graft substitutes were prepared from aliphatic segmented poly(ester urethane) urea using the phase-inverse technique. Proton nuclear magnetic resonance, size-exclusion chromatography, electron spectroscopy for chemical analysis, secondary ion mass spectrometry, infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, computed tomography and mechanical tests were carried out, to characterize the scaffolds' physicochemical properties. Human osteosarcoma MG-63 cells were seeded into the scaffolds for 1, 2, 3 and 4weeks to evaluate their potential to support attachment, growth and proliferation of osteogenic cells. The scaffold-cell interaction was assessed by analysis of DNA content, total protein amount, alkaline phosphatase activity and WST-1 assay. The scaffolds supported cell attachment, growth and proliferation over the whole culture period of 4weeks (DNA, total protein amount). There was, however, a reduction in the WST-1 assay values at 4weeks, which might suggest a reduction in the rate of cell proliferation at this time.

Farnesol-modified biodegradable polyurethanes for cartilage tissue engineering.

A bifunctionalized 3,7,11-trimethyl-2,6,10-dodecatrien-1-diaminobutane amide (isoprenoid) was obtained from 3,7,11-trimethyl-2,6,10-dodecatrien-1-ol (farnesol) in a three-step synthesis. The bifunctionalized isoprenoid was characterized using infrared spectroscopy and (1)H and (13)C nuclear magnetic resonance spectroscopy and was covalently incorporated (0.12 mmol x g(-1)) into the biodegradable aliphatic polyurethane formed on the polycondensation reaction of poly(epsilon-caprolactone) diol, 1,4,3,6-dianhydro-D-sorbitol and 1,6-hexamethylene diisocyanate. Although the covalent incorporation of the isoprenoid molecule into the polyurethane chain modified the surface chemistry of the polymer, it did not affect the viability of attached chondrocytes. Porous 3D scaffolds were produced from the modified and unmodified biodegradable segmented polyurethanes by a salt leaching-phase-inverse technique. The scaffolds were seeded with bovine chondrocytes encapsulated in fibrin gel and cultured in vitro for 14 days. The incorporation of bifunctional isoprenoid into the polyurethane affected the morphology of the scaffolds produced, when compared with the morphology of the scaffolds produced using the same technique from the unmodified polyurethane. As a consequence, there was more uniform cell seeding and more homogeneous distribution of the synthesized extracellular matrix throughout the scaffold resulting in a reduced cell/tissue layer at the edges of the constructs. However, glycosaminoglycan (GAG), DNA content, and chondrocytes phenotype in the scaffolds produced from these two polyurethane formulations did not vary significantly. The findings suggest that the change of surface characteristics and the more open pore structure of the scaffolds produced from the isoprenoid-modified polyurethane are beneficial for the seeding efficiency and the homogeneity of the tissue engineered constructs.

Microporous biodegradable polyurethane membranes for tissue engineering.

Microporous membranes with controlled pore size and structure were produced from biodegradable polyurethane based on aliphatic diisocyanate, poly(epsilon-caprolactone) diol and isosorbide chain extender using the modified phase-inversion technique. The following parameters affecting the process of membrane formation were investigated: the type of solvent, solvent-nonsolvent ratio, polymer concentration in solution, polymer solidification time, and the thickness of the polymer solution layer cast on a substrate. The experimental systems evaluated were polymer-N,N-dimethylformamide-water, polymer-N,N-dimethylacetamide-water and polymer-dimethylsulfoxide-water. From all three systems evaluated the best results were obtained for the system polymer-N,N-dimethylformamide-water. The optimal conditions for the preparation of microporous polyurethane membranes were: polymer concentration in solution 5% (w/v), the amount of nonsolvent 10% (v/v), the cast temperature 23 degrees C, and polymer solidification time in the range of 24-48 h depending on the thickness of the cast polymer solution layer. Membranes obtained under these conditions had interconnected pores, well defined pore size and structure, good water permeability and satisfactory mechanical properties to allow for suturing. Potential applications of these membranes are skin wound cover and, in combination with autogenous chondrocytes, as an "artificial periosteum" in the treatment of articular cartilage defects.

Reconstruction of mandibular segmental defects using the guided-bone regeneration technique with polylactide membranes and/or autogenous bone graft: a preliminary study on the influence of membrane permeability.

PURPOSE: Bone maintenance after mandibular reconstruction with autogenous iliac crest may be disappointing due to extensive resorption in the long term. The potential of the guided-bone regeneration (GBR) technique to enhance the healing process in segmental defects lacks comprehensive scientific documentation. This study aimed to investigate the influence of polylactide membrane permeability on the fate of iliac bone graft (BG) used to treat mandibular segmental defects. MATERIALS AND METHODS: Unilateral 10-mm-wide segmental defects were created through the mandibles of 34 mongrel dogs. All defects were mechanically stabilized, and the animals were divided into 6 treatment groups: control, BG alone, microporous membrane (poly L/DL-lactide 80/20%) (Mi); Mi plus BG; microporous laser-perforated (15 cm(2) ratio) membrane (Mip), and Mip plus BG. Calcein fluorochrome was injected intravenously at 3 months, and animal euthanasia was carried out at 6 months postoperatively. RESULTS: Histomorphometry showed that BG protected by Mip was consistently related to larger amounts of bone compared with other groups (P

The use of long-chain plant polyprenols as a means to modify the biological properties of new biodegradable polyurethane scaffolds for tissue engineering. A pilot study.

Microporous membranes for tissue engineering were produced from new biodegradable polyurethane based on hexamethylene diisocyanate, poly(epsilon-caprolactone) diol and 1,4:3,6-dianhydro-D-sorbitol. The interconnected pores had an average size in the range of 5-100 microm. The tensile strength at break, the Young's modulus and elongation at break of the membranes were 3.2+/-0.3 MPa, 25.2+/-1.5 MPa and 190+/-12%, respectively, while nonporous foils from the same polymers had a tensile strength at break of 40+/-2 MPa, a Young's modulus of 91+/-6 MPa, and an elongation at break of 370+/-10%. The membranes were incubated for 10 days in a 2.65 vol% solution of long-chain plant polyprenol in n-hexane to promote their interaction with cells and tissues. The polyprenol was isolated from leaves of Magnolia cobus and was a mixture of prenol-10 and prenol-11. The prenol-impregnated membranes and nonimpregnated membranes (control) were tested in cell culture to assess whether impregnation has a beneficial effect on cell-material interaction. The cells used in the test were chondrocytes isolated from the articular-epiphyseal cartilage of leg bones of 5-day-old inbred LEW rats. The time of culture was 2 and 5 weeks. Both, the nonimpregnated and impregnated polyurethane membranes supported attachment and growth of rat chondrocytes. The cells firmly attached to the surface of the microporous membranes, invaded the pores and maintained the round shape characteristic for chondrocyte-like-morphology. Abundant fibrillar extracellular matrix produced by the cells resembled the network formed by chondrocytes in vivo. The cells produced relatively more extracellular matrix in the membranes impregnated with polyprenol than in the control membranes. Impregnation of polyurethane scaffolds with biologically active amphiphilic polyprenols may be a route to facilitate the cell-material interaction.

Structure-property relations and cytotoxicity of isosorbide-based biodegradable polyurethane scaffolds for tissue repair and regeneration.

Microporous scaffolds with potential applications for tissue engineering were produced from the biodegradable aliphatic isosorbide-based polyurethane using a combined salt leaching-solvent evaporation-coagulation process. Alkaline sodium phosphate heptahydrate crystals were used as a solid porogene, and acetone-water mixture was used as a nonsolvent-coagulant. The scaffolds used in this study had interconnected pores with sizes in the range of 70-120 microm and a pore-to-volume ratio of 87%. The XPS measurements showed that the residence of the scaffold in an aqueous solution of the alkaline porogene changed its surface atomic composition, that is increased the surface concentration of oxygen and nitrogen and reduced the surface concentration of hydrocarbons relative to the control material. This also enhanced the hydrophilicity of the scaffold's surfaces as assessed from contact angle measurements. The alkaline porogene did not affect the polymer's molecular weight. The MTT cytotoxicity assay showed that the isosorbide-based polyurethane scaffold is noncytotoxic. The amounts of interleukin-6 and interleukin-8 proinflammatory cytokines released from human blood leukocytes exposed to the polyurethane scaffolds in vitro were comparable and/or lower than the amount of the cytokines released by leukocytes exposed to the culture-grade polystyrene control.

Biodegradable polyurethane cancellous bone graft substitutes in the treatment of iliac crest defects.

Porous scaffolds were produced from newly designed biodegradable, segmented aliphatic polyurethanes of various chemical compositions and hydrophilic-to-hydrophobic segment ratios. The scaffolds were implanted into monocortical defects in the iliac crest of healthy sheep for 6 months. The resected cortex was not repositioned. The ilium defects, which were not implanted with polyurethane scaffolds, were used as controls. In none of the control defects was there bone regeneration at the time of euthanasia. The defects implanted with porous scaffolds from polyurethanes were healed to varying extents with cancellous bone. The structure of the regenerated cancellous bone was radiographically denser than the structure of native bone. New bone that was formed in the scaffolds with a higher amount of hydrophilic component contained more calcium phosphate deposit than the bone formed in the scaffolds with a lower amount of the hydrophilic component. There was no new cortex formed over the defect, but a thin layer of soft tissue covered the newly formed cancellous bone.

Biodegradable elastomeric polyurethane membranes as chondrocyte carriers for cartilage repair.

Autologous chondrocyte implantation in combination with an autologous periosteal patch has become a clinically accepted procedure for the treatment of articular cartilage defects. The use of periosteum has, however, several drawbacks. We have been able to fabricate thin elastomeric biodegradable polyurethane (PU) membranes that may possibly have an application as a tissue-engineered substitute for the periosteal patch. Three types of membranes varying in pore size and surface texture were used as substrates for bovine chondrocytes in culture. The membranes, marked as P-I, P-II, and P-R, had average pore sizes of 10 to 20 microm, 40 to 60 microm, and less than 5 microm, respectively. A poly(L/DL-lactide) 80/ 20% micro-porous membrane (PLA) with an average pore size in the range of 10 to 70 microm was used as a control. There was no difference in the cell proliferation profile among the 4 membranes. In terms of proteoglycan and collagen production, P-I, P-R, and PLA performed similarly to one another. The rate of matrix production appears to be greater in the PU membranes than in the PLA membrane in the first 10 days, although by day 30, the PLA membrane had caught up. In all comparisons, the performance of P-II lagged behind those of the other materials. In conclusion, this preliminary study supports the potential use of this novel group of PUs as a periosteal flap substitute or perhaps as a chondrocyte carrier for matrix-assisted chondrocyte implantation and related techniques. Further studies will be necessary to better define their role in clinical applications for cartilage repair.

Mechanical and radiological assessment of the influence of rhTGFbeta-3 on bone regeneration in a segmental defect in the ovine tibia: pilot study.

Limitations in the use of autologous bone graft, which is the gold standard therapy in bone defect healing, drive the search for alternative treatments. In this study the influence of rhTGFbeta-3 on mechanical and radiological parameters of a healing bone defect in the sheep tibia was assessed. In the sheep, an 18-mm long osteoperiosteal defect in the tibia was treated by rhTGFbeta-3 seeded on a poly(L/DL-lactide) carrier (n = 4). In a second group (n = 4), the defect was treated by the carrier only, in a third group (n = 4) by autologous cancellous bone graft, and in a fourth group (n = 2) the defect remained blank. The healing process of the defect was assessed by weekly in vivo stiffness measurements and radiology as well as by quantitative computed tomographic assessment of bone mineral density (BMD) every 4 weeks. The duration of the experiment was 12 weeks under loading conditions. In the bone graft group, a marginally significant higher increase in stiffness was observed than in the PLA/rhTGFbeta-3 group (p = 0.06) and a significantly higher increase than in the PLA-only group (p = 0.03). The radiographic as well as the computed tomographic evaluation yielded significant differences between the groups (p = 0.03), indicating the bone graft treatment (bone/per area, 83%; BMD, 0.57 g/cm(3)) performing better than the PLA/rhTGFbeta-3 (38%; 0.23 g/cm(3)) and the PLA-only treatment (2.5%; 0.09 g/cm(3)), respectively. Regarding the mechanical and radiological parameters assessed in this study, we conclude that rhTGFbeta-3 has a promoting effect on bone regeneration. However, under the conditions of this study, this effect does not reach the potential of autologous cancellous bone graft transplantation.

Biodegradable porous polyurethane scaffolds for tissue repair and regeneration.

Critical-size bone defects usually require the insertion of autogenous bone graft to heal. Harvesting of bone is traumatic and results in high morbidity at the donor site. A potential alternative to bone graft may be a bone substitute with adequate biocompatibility and biological properties produced from ceramics or bioresorbable/biodegradable polymers. In the present study, new elastomeric biodegradable polyurethanes with an enhanced affinity toward cells and tissues were synthesized using aliphatic diisocyanate, poly(epsilon-caprolactone) diol, and biologically active 1,4:3,6-dianhydro-D-sorbitol (isosorbide diol) as chain extender. The polymers were processed into 3D porous scaffolds by applying a combined salt leaching-phase inverse process. The critical parameters controlling pore size and geometry were the solvents and nonsolvents used for scaffold preparation and the sizes of the solid porogen crystals. Scaffolds prepared from the polymer solution in solvents such as dimethylsulfoxide or methyl-2-pyrrolidone did not have a homogenous pore structure. Many pores were interconnected, but numerous pores were closed. Irrespective of the high pore-to-volume ratio (75%), the scaffolds showed poor water permeability. The best solvent for the preparation of scaffolds from the polyurethane used in the study was dimethylformamide (DMF). The type of nonsolvent admixed to the polymer solution in DMF strongly affected the scaffolds' pore structure. The elastomeric polyurethane scaffold prepared from the optimal solvent-nonsolvent mixture had regular interconnected pores, high water permeability, and a pore-to-volume ratio of 90%. The osteoconductive properties of the 3D porous polyurethane scaffolds can be additionally promoted by loading them with calcium phosphate salts such as hydroxyapatite or tricalcium phosphate, thus making them promising candidates for bone graft substitutes.

Regeneration of bicortical defects in the iliac crest of estrogen-deficient sheep, using new biodegradable polyurethane bone graft substitutes.

Porous scaffolds for cancellous bone graft substitutes were prepared from new experimental biodegradable aliphatic polyurethane elastomers with varying hydrophilicity. The ratios of the hydrophilic-to-hydrophobic content in the polymers were 30-70, 50-50, and 70-30%, respectively. The hydrophilic component consisted of poly(ethylene oxide) diol and the hydrophobic component of poly(epsilon-caprolactone) diol. To promote the materials' biological performance, the calcium complexing moiety, the polysaccharide, and vitamin D(3) were incorporated into the polymer chain upon synthesis. The scaffolds had an interconnected porous structure with an average pore size in the range of 300-2,000 microm and pore-to-volume ratios of (85 +/- 5)%. The bone substitutes were implanted (press-fit) in biocortical 10 x 10 mm(2) defects created in the tuber coxae of 21 skeletally mature Warhill ewes, which were ovariectomized 12 months prior to implantation. At the time of euthanasia at 18 and 25 months, all the defects in the ilium implanted with polyurethane bone substitutes had healed with new bone. The extent of bone healing depended on the chemical composition of the polymer from which the implant was made, although for the same material there were animal-related differences in healing. The structure of the newly formed cancellous bone was radiographically and histologically similar to the native bone. The implants from polymers with the incorporated calcium-complexing additive were the most effective promoters of bone healing, followed by those with vitamin D(3) and polysaccharide-containing polymer. There was no bone healing in the control defects.

Influence of copolymer composition of polylactide implants on cranial bone regeneration.

Biodegradable polymers have become useful auxiliary materials for the functional and structural restoration of bone deficiencies. Commercial implants from poly(L/DL-lactide) 70:30 are used clinically for fracture fixation in regions of low load. Implants manufactured from poly(L/DL-lactide) 80:20 are currently being investigated experimentally. The higher degree of crystallinity results in a higher chemical strength and loading capacity which promises advantages for long-term implantation. In this study implants from these two copolymers were applied to promote bone regeneration of bilateral, full thickness, circular cranial defects in 16 adult New Zealand white rabbits. The defects were covered with melt extruded and laser cut polylactide burr hole covers epicranially and endocranially in direct contact to the dura. The defect spaces were kept open with a spacer which created a hollow chamber. Both materials were implanted in each animal. Bone seeking fluorochromes were used to assess the pattern of bone growth. After eight weeks bone regeneration in the defects was assessed radiologically, histologically and by fluorescence microscopy. During the eight weeks observation period the application of a hollow chamber design resulted in almost complete cranial defect healing, whereby the copolymer composition had no effect on the amount or the morphology of the regenerate. The dura mater showed no adverse tissue reactions during these early stages of implantation. Eight weeks is only a short period in the lifetime of the tested polymers and complete bone regeneration can only be expected after complete polymer degradation. Long-term studies or accelerated degradation studies are required to confirm the expected advantages of poly(L/DL-lactide) 80:20.

Attachment, growth, and activity of rat osteoblasts on polylactide membranes treated with various low-temperature radiofrequency plasmas.

Nonporous and porous membranes from poly(L/DL-lactide) 80/20% were treated with low-temperature oxygen, ammonia, or sulphur dioxide-hydrogen plasmas and the late effects of plasma treatment on physicochemical characteristics of the membranes' surface were analyzed. The plasma treatment resulted in the permanent attachment of sulphur and nitrogen functionalities to the membrane's surface, and increased the surface concentration of oxygen, thereby increasing the surface wettability. To assess whether the plasma treatment affects the cellular response, primary rat osteoblasts were cultured on nontreated and plasma-treated nonporous and microporous membranes, and attachment, growth, and activity of cells were investigated. It was found that attachment and growth of osteoblasts on all the plasma-treated membranes were greater compared with nontreated controls. The treatment with ammonia plasma was most efficacious. The beneficial effects of plasma treatment on cells were most pronounced for microporous polylactide membranes irrespective of the plasma used. The results of the study suggest that the treatment of porous polylactide structures with plasma can be an effective means of enhancing their suitability for tissue engineering. Plasma exposure may also have an advantageous effect on bone healing when polylactide membranes are used to treat bone defects.

Effects of simple and complex motion patterns on gene expression of chondrocytes seeded in 3D scaffolds.

This study investigated the effect of unidirectional and multidirectional motion patterns on gene expression and molecule release of chondrocyte-seeded 3D scaffolds. Resorbable porous polyurethane scaffolds were seeded with bovine articular chondrocytes and exposed to dynamic compression, applied with a ceramic hip ball, alone (group 1), with superimposed rotation of the scaffold around its cylindrical axis (group 2), oscillation of the ball over the scaffold surface (group 3), or oscillation of ball and scaffold in phase difference (group 4). Compared with group 1, the proteoglycan 4 (PRG4) and cartilage oligomeric matrix protein (COMP) mRNA expression levels were markedly increased by ball oscillation (groups 3 and 4). Furthermore, the collagen type II mRNA expression was enhanced in the groups 3 and 4, while the aggrecan and tissue inhibitor of metalloproteinase-3 (TIMP-3) mRNA expression levels were upregulated by multidirectional articular motion (group 4). Ball oscillation (groups 3 and 4) also increased the release of PRG4, COMP, and hyaluronan (HA) into the culture media. This indicates that the applied stimuli can contribute to the maintenance of the chondrocytic phenotype of the cells. The mechanical effects causing cell stimulation by applied surface motion might be related to fluid film buildup and/or frictional shear at the scaffold-ball interface. It is suggested that the oscillating ball drags the fluid into the joint space, thereby causing biophysical effects similar to those of fluid flow.

Fibrin-polyurethane composites for articular cartilage tissue engineering: a preliminary analysis.

In this study we investigated the use of a fibrin hydrogel to improve the potential of a polyurethane (PU) scaffold-based system for articular cartilage tissue engineering. PU-only ("no-fibrin") and PU-fibrin ("fibrin") composites were cultured for up to 28 days and analyzed for DNA content, glycosaminoglycan (GAG) content, type II collagen content, GAG release, and gene expression of aggrecan, collagen I, and collagen II. The use of fibrin allowed for higher viable cell-seeding efficiency (10% higher DNA content on day 2 in fibrin versus no-fibrin composites) and more even cell distribution on seeding, a more than 3-fold increase in the percentage of newly synthesized GAG retained in the constructs, and 2- to 6-fold higher levels of type II collagen and aggrecan gene expression through day 14. Addition of aprotinin to the medium inhibited fibrin degradation, most noticeably in the center of the constructs, but had little effect on biochemical composition or gene expression. Short-term mechanical compression (0-10% sinusoidal strain at 0.1 Hz for 1 h, applied twice daily for 3 days) doubled the rate of GAG release from the constructs, but had little effect on gene expression, regardless of the presence of fibrin. Although further work is needed to optimize this system, the addition of fibrin hydrogel to encapsulate cells in the stiff, macroporous PU scaffold is a step forward in our approach to articular cartilage tissue engineering.

Early dural reaction to polylactide in cranial defects in rabbits.

Restoring the bone integrity to injured calvariae remains a challenge to surgeons. In this study, the dural biocompatibility of biodegradable poly-L/DL-lactide 80/20 and 70/30 defect covers, designed for guided bone regeneration, was assessed. In each of the 16 test rabbits, bilateral (8.3 mm) cranial defects were created. The different covers were applied to one defect each in every rabbit and consisted of three parts: an epicranial cover, a spacer, and a dural cover. All defects had closed after 8 weeks due to new bone formation. A few giant cells were found at the cover-to-dura interface in equal numbers for both covers. Dural bone formation was present in 15 of 16 rabbits and progressed unhindered by the defect cover or its early degradation products.

The in vitro growth and activity of sheep osteoblasts on three-dimensional scaffolds from poly(L/DL-lactide) 80/20%.

Critical-size bone defects usually require the use of autogenous bone grafts to heal. Harvesting of bone is traumatic, and results in high morbidity of donor site. A potential alternative to bone graft may be a bone substitute with adequate biocompatibility and biological properties produced from ceramics and/or bioresorbable or biodegradable polymers. In the present study, sheep osteoblasts isolated from cancellous bone chips were seeded and cultured for 1, 2, and 3 weeks on porous poly(L/DL-lactide) 80/20% scaffolds. The cell morphology was assessed from rhodamine staining and scanning electron microscopy, cell growth, and activity from the measurements of DNA, alkaline phosphatase activity, and total protein amount in the cell lysate, and mineral deposits from EDAX and van Kossa staining. The cells attached firmly to the scaffold walls, grew deeply into the pores, and exhibited morphology typical of osteoblasts. Mineralized noduli with a Ca/P ratio of 1.4 to 1.8 found in the scaffold indicated that the cells had maintained their osteoblastic phenotype. The amount of DNA, alkaline phosphatase activity, and the total amount of proteins increased with time of culturing, although at 3 weeks the cells did not yet reach the contact inhibition. These results demonstrate that three-dimensional porous poly(L/DL-lactide) 80/20% scaffolds provide a suitable substrate for the attachment and growth of primary osteoblasts, and might potentially be used as bone defect fillers and in the design of tissue-engineered bone substitutes.

Surface motion upregulates superficial zone protein and hyaluronan production in chondrocyte-seeded three-dimensional scaffolds.

A cartilage engineering bioreactor has been developed that provides joint-specific kinematics. This study investigated the effect of articular motion on the gene expression of superficial zone protein (SZP) and hyaluronan synthases (HASs) and on the release of SZP and hyaluronan of chondrocytes seeded onto biodegradable scaffolds. Cylindrical (8 x 4 mm) porous polyurethane scaffolds were seeded with bovine articular chondrocytes and subjected to static or dynamic compression, with and without articulation against a ceramic hip ball. After loading, the mRNA expression of SZP and HASs was analyzed, and SZP immunoreactivity and hyaluronan concentration of conditioned media were determined. Surface motion significantly upregulated the mRNA expression of SZP and HASs. Axial compression alone had no effect on SZP and increased HAS mRNA only at high strain amplitude. SZP was immunodetected only in the media of constructs exposed to surface motion. The release of hyaluronan into the culture medium was significantly enhanced by surface motion. These results indicate that specific stimuli that mimic the kinematics of natural joints, such as articular motion, may promote the development of a functional articular surface-synovial interface.

Tribology approach to the engineering and study of articular cartilage.

This study has been based on the assumption that articular motion is an important aspect of mechanotransduction in synovial joints. For this reason a new bioreactor concept, able to reproduce joint kinematics more closely, has been designed. The prototype consists of a rotating scaffold and/or cartilage pin, which is pressed onto an orthogonally rotating ball. By oscillating pin and ball in phase difference, elliptical displacement trajectories are generated that are similar to the motion paths occurring in vivo. Simultaneously, dynamic compression may be applied with a linear actuator, while two-step-motors generate the rotation of pin and ball. The whole apparatus is placed in an incubator. The control station is located outside. Preliminary investigations at the gene expression level demonstrated promising results. Compared with free-swelling control and/or simply compression-loaded samples, chondrocyte-seeded scaffolds as well as nasal cartilage explants exposed to interface motion both showed elevated levels of cartilage oligomeric matrix protein mRNA. The final design of the bioreactor will include four individual stations in line, which will facilitate the investigation of motion-initiated effects at the contacting surfaces in more detail.