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Osteochondral (OC) scaffold-based regenerative approaches in the joint are challenging since the scaffold must provide mechanical strength while also mimicking the local cartilage and bone microenvironments. Thermally Induced Phase Separation (TIPS) can produce scaffolds with a wide range of pore size morphologies/distributions. Here, we produced by TIPS a poly-L-lactide (PLL A) scaffold with a continuous pore size gradient along the sample thickness, from ~70μm diameter on one side to ~200 μm diameter on the opposite surface.

A microphysiological tissue system (MPS) bioreactor has been developed to replicate in vitro the in vivo OC physiological conditions. The MPS allows separate control of the chondral and osseous environment while permitting communication between chondrocytes and osteoblasts across the OC junction, similar to the conditions of OC tissue in vivo. We have used here our MPS system to validate the TIPS -generated pore-gradient PLLA scaffold.

Cartilage and bone tissues in the joints are intimately linked and form the osteochondral unit. A better understanding of both disease and regenerative processes of bone and cartilage requires the study of both tissues together, as part of the osteochondral unit to account for their mutual interactions. However, the production of scaffolds for osteochondral tissue regeneration is a challenging task, since scaffolds must mimic the differents morphologies of cartilage and bone. Thermally Induced Phase Separation (TIPS) is one of the most adaptable techniques to produce porous scaffold for Tissue Engineering applications. A wide range of morphologies in terms of both pore size and distribution can be obtained by tuning TIPS processing parameters, primarily thermal history. We used TIPS to produce scaffolds for osteochondral tissue engineering with a pore size that increases along the sample thickness. The pore dimension on one side of the sample was about 70 micron and increased steadily without interruption until it reached about 220 micron on the opposite surface. These scaffolds were tested in a microphysiological tissue system bioreactor. The bioreactor consists of a dual chamber system to maintain separate chondrogenic/osteogenic specific differentiation media. A removable insert hosted the scaffold seeded with human bone marrow-derived mesenchymal stem cells. The insert with the gradient pore scaffold was positioned so that the smaller pore side was in the chondrogenic medium chamber and the larger pore size was in the osteogenic medium chamber. An O-ring around the insert ensured the separation of the media streams in the dual chamber system. This setup provides separate tissue-specific growth media for the cartilaginous/osseous differentiation of MSCs in the osteochondral scaffold. Preliminary tests show a good efficiency of cell seeding and growth, and the bioreactor with the TIPS scaffold allows to reproduce the physiological conditions to better mimic osteochondral tissues.

Damage to cartilage is of great clinical consequence given the tissue's limited intrinsic potential for healing. Current treatments for cartilage repair are less than satisfactory, and rarely restore full function or return the tissue to its native normal state. The rapidly emerging field of tissue engineering holds great promise for the generation of functional cartilage tissue substitutes. The general approach involves a biocompatible, structurally and mechanically sound scaffold, with an appropriate cell source, which is loaded with bioactive molecules that promote cellular differentiation and/or maturation. This review highlights aspects of current progress in cartilage tissue engineering.

To conduct a multicenter study to validate the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE) II system, APACHE III system, Trauma and Injury Severity Score (TRISS) methodology, and a 24-hour intensive care unit (ICU) point system for prediction of mortality in ICU trauma patient admissions.The study population consisted of retrospectively identified, consecutive ICU trauma admissions (n = 2,414) from six Level I trauma centers. Probabilities of death were calculated by using logistic regression analysis. The predictive power of each system was evaluated by using decision matrix analysis to compare observed and predicted outcomes with a decision criterion of 0.50 for risk of hospital death. The Youden Index (YI) was used to compare the proportion of patients correctly classified by each system. Measures of model calibration were based on goodness-of-fit testing (Hosmer-Lemeshow statistic less than 15.5) and model discrimination were based on the area under the receiver operating characteristic curve (AUC).Overall, APACHE II (sensitivity, 38%; specificity, 99%; YI, 37%; H-L statistic, 92.6; AUC, 0.87) and TRISS (sensitivity, 52%; specificity, 94%; YI, 46%; H-L statistic, 228.1; AUC, 0.82) were poor predictors of aggregate mortality, because they did not meet the acceptable thresholds for both model calibration and discrimination. APACHE III (sensitivity, 60%; specificity, 98%; YI, 58%; H-L statistic, 7.0; AUC, 0.89) was comparable to the 24-hour ICU point system (sensitivity, 51%; specificity, 98%; YI, 50%; H-L statistic, 14.7; AUC, 0.89) with both systems showing strong agreement between the observed and predicted outcomes based on acceptable thresholds for both model calibration and discrimination. The APACHE III system significantly improved upon APACHE II for estimating risk of death in ICU trauma patients (p0.001). Compared with the overall performance, for the subset of patients with nonoperative head trauma, the percentage correctly classified was decreased to 46% for APACHE II; increased to 71% for APACHE III (p0.001 vs. APACHE II); increased to 59% for TRISS; and increased to 62% for 24-hour ICU points. For operative head trauma, the percentage correctly classified was increased to 60% for APACHE II; increased to 61% for APACHE III; decreased to 43% for TRISS (p0.004 vs. APACHE III); and increased to 54% for 24-hour ICU points. For patients without head injuries, all of the systems were unreliable and considerably underestimated the risk of death. The percentage of nonoperative and operative patients without head trauma who were correctly classified was decreased, respectively, to 26% and 30% for APACHE II; 33% and 29% for APACHE III; 33% and 19% for TRISS; 20% and 23% for 24-hour ICU points.For the overall estimation of aggregate ICU mortality, the APACHE III system was the most reliable; however, performance was most accurate for subsets of patients with head trauma. The 24-hour ICU point system also demonstrated acceptable overall performance with improved performance for patients with head trauma. Overall, APACHE II and TRISS did not meet acceptable thresholds of performance. When estimating ICU mortality for subsets of patients without head trauma, none of these systems had an acceptable level of performance. Further multicenter studies aimed at developing better outcome prediction models for patients without head injuries are warranted, which would allow trauma care providers to set uniform standards for judging institutional performance.

Fragestellung: Der Erfolg matrix-basierter Verfahren zur Rekonstruktion fokaler Gelenkknorpeldefekte hängt von der lateralen Integration des implantierten Konstruktes in den umgebenden Geklenkknorpel und der Synthese knorpelspezifischer Extrazellulärmatrix durch die transplantierten Zellen[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie; 73. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 95. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 50. Tagung des Berufsverbandes der Fachärzte für Orthopädie

A porous, biodegradable polymer composite was fabricated from poly(L-lactic acid) (PLLA) using a solvent- casting particulate-leaching technique, and loaded with recombinant human transforming growth factor ß-1 (TGF-ß1). Tissue culture polystyrene (TCPS) and PLLA disks loaded with bovine serum albumin (BSA) served as controls. Polymer specimens were seeded at high cell density with C3H10T1/2 cells, a mouse embryonic cell line capable of differentiating into various connective tissue cell types. The polymer matrices degraded slowly in physiological saline over four weeks, with a sustained yet sporadic release of active TGF-ß1; a more controlled release of TGF-ß1 was observed in serum-containing culture medium and with cell seeding. Compared to controls, cells seeded on TGF-ß1-Ioaded PLLA disks showed significantly enhanced DNA and proteoglycan synthesis, while collagen biosynthesis was greater in all PLLA cultures compared to those on TCPS. Scanning electron microscopy revealed extensive cell proliferation, with a chondrocyte-like phenotype, throughout the porous matrix, while histology showed intact cell bodies and minimal cellular necrosis. These results suggest that the TGF-ß1-loaded cell-polymer composite supports cell proliferation/differentiation, and is a candidate template for connective tissue engineering.