Nickel-titanium is a functional alloy currently used in various clinical applications, especially in vascular stents. There is an increased interest in the orthopaedic use of NiTi-based implants. The alloy enables the manufacture of applications of constant load, controllable motion, and minimal invasiveness. NiTi is considered biocompatible and it possesses mechanical properties that make it an especially good candidate for bone tissue surroundings. In our studies, we have investigated the effects of surface properties of NiTi on its biocompatibility. The martensitic phase was shown to have lower biocompatibility of material in comparison with austenitic NiTi. Cellular cytotoxicity increased and cell adhesion diminished on martensite phase. This was observed with both osteoblasts and osteoclasts. Our studies showed that the thickness of the oxide layer does not necessarily enhance the biocompatibility. The surface state of NiTi is strongly affected by thermal oxidation. Surface properties affect the initial adsorption of proteins and other macromolecules onto the biomaterial surface; this in turn impacts the following cellular responses, such as proliferation and differentiation, which are dictated by adhesion to the extracellular matrix components. Since adhesive force is connected to the interaction with the adsorbed molecules, it might be an important factor in the biocompatibility. Sol-gel derived titania-silica surface treatment was observed to increase the bone-implant coating of functional intramedullary NiTi nails. Sol-gel treatment together with the bending force increased the fixation of the implant (osseointegration). These studies indicate that the surface properties of NiTi are important for its biocompatibility.
Articular cartilage repair is assumed to improve by covering the cartilage lesion with a biomaterial scaffold tailored to the specific requirements of the weight-bearing joint surface. We have tested the feasibility of a novel composite collagen-polylactide scaffold rhCo-PLA in cartilage repair. To confirm these results and further challenge the scaffold, we tested it in a large porcine cartilage defect. A critical-sized full-thickness chondral defect was made in the medial femoral condyle of 18 domestic pigs. This technically widest possible defect size of 11×17 mm was determined in a pilot test. Five weeks later, the defect was either treated with the novel rhCo-PLA scaffold or left untreated to heal spontaneously. After four months, the medial condyles were evaluated macroscopically using Goebel's score, in which the worst possible result receives a total of 20 points and imaged with µCT to evaluate subchondral bone. Macroscopic score and subchondral bone microstructure were similar in both study group...
Use of scaffolds for articular cartilage repair (ACR) has increased over the last years with many biomaterials options suggested for this purpose. It is known that scaffolds for ACR have to be opti...
Abstract Cell therapy combined with biomaterial scaffolds is used to treat cartilage defects. We hypothesized that chondrogenic differentiation bone marrow‐derived mesenchymal stem cells (BM‐MSCs) in three‐dimensional biomaterial scaffolds would initiate cartilaginous matrix deposition and prepare the construct for cartilage regeneration in situ. The chondrogenic capability of human BM‐MSCs was first verified in a pellet culture. The BM‐MSCs were then either seeded onto a composite scaffold rhCo‐PLA combining polylactide and collagen type II (C2) or type III (C3), or commercial collagen type I/III membrane (CG). The BM‐MSCs were either cultured in a proliferation medium or chondrogenic culture medium. Adult human chondrocytes (ACs) served as controls. After 3, 14, and 28 days, the constructs were analyzed with quantitative polymerase chain reaction and confocal microscopy and sulfated glycosaminoglycans (GAGs) were measured. The differentiated BM‐MSCs entered a hypertrophic state by Day 14 of culture. The ACs showed dedifferentiation with no expression of chondrogenic genes and low amount of GAG. The CG membrane induced the highest expression levels of hypertrophic genes. The two different collagen types in composite scaffolds yielded similar results. Regardless of the biomaterial scaffold, culturing BM‐MSCs in chondrogenic differentiation medium resulted in chondrocyte hypertrophy. Thus, caution for cell fate is required when designing cell‐biomaterial constructs for cartilage regeneration.
Objective Large articular cartilage defects are a challenge to regenerative surgery. Biomaterial scaffolds might provide valuable support for restoration of articulating surface. The performance of a composite biomaterial scaffold was evaluated in a large porcine cartilage defect. Design Cartilage repair capacity of a biomaterial combining recombinant human type III collagen (rhCo) and poly-(l/d)-lactide (PLA) was tested in a porcine model. A full-thickness chondral defect covering the majority of the weightbearing area was inflicted to the medial femoral condyle of the right knee. Spontaneous cartilage repair and nonoperated healthy animals served as controls. The animals were sacrificed after a 4-month follow-up. The repair tissue was evaluated with the International Cartilage Repair Society (ICRS) macroscopic score, ICRS II histological score, and with micro-computed tomography. Additionally, histopathological evaluation of lymph nodes and synovial samples were done for toxicological analyses. Results The lateral half of the cartilage defect in the operated groups showed better filling than the medial half. The mean overall macroscopic score for the rhCo-PLA, spontaneous, and nonoperated groups were 5.96 ± 0.33, 4.63 ± 0.42, and 10.98 ± 0.35, respectively. The overall histological appearance of the specimens was predominantly hyaline cartilage in 3 of 9 samples of the rhCo-PLA group, 2 of 8 of the spontaneous group, and 9 of 9 of the nonoperated group. Conclusions The use of rhCo-PLA scaffold did not differ from spontaneous healing. The repair was affected by the spatial properties within the defect, as the lateral part of the defect showed better repair than the medial part, probably due to different weightbearing conditions.
Abstract Articular cartilage regeneration is a challenge in tissue engineering. Although diverse materials have been developed for this purpose, cartilage regeneration remains suboptimal. The integration of nanomaterials into 3D network materials holds great potential in the improvement of key mechanical properties, particularly important for osteochondral replacement scaffolds and even to function as carriers for disease‐modifying drugs or other regulatory signals. In this study, a simple yet effective cell‐free nanoenabled Col‐PLA scaffold specially designed to enhance cartilage regeneration and modulate inflammatory response is proposed, by incorporating poly(lactic‐co‐glycolic acid) (PLGA) ibuprofen nanoparticles (NPs) into a collagen/polylactide (Col‐PLA) matrix. The developed nanoenabled scaffold successfully decreases IL‐1β release and leads to primary human chondrocytes survival, ultimately restoring extracellular matrix (ECM) production under inflammatory conditions. The nanoenabled Col‐PLA scaffolds secretome effectively decreases macrophage invasion in vitro, as well as neutrophil infiltration and inflammatory mediators’, namely the complement component C5/C5a, C‐reactive protein, IL‐1β, MMP9, CCL20, and CXCL1/KC production in vivo in a rodent air‐pouch model. Overall, the established nanoenabled scaffold has the potential to support chondrogenesis as well as modulate inflammatory response, overcoming the limitations of traditional tissue engineering strategies.
Scaffolds for articular cartilage repair have to be optimally biodegradable with simultaneous promotion of hyaline cartilage formation under rather complex biomechanical and physiological conditions. It has been generally accepted that scaffold structure and composition would be the best when it mimics the structure of native cartilage. However, a reparative construct mimicking the mature native tissue in a healing tissue site presents a biological mismatch of reparative stimuli. In this work, we studied a new recombinant human type III collagen-polylactide (rhCol-PLA) scaffolds. The rhCol-PLA scaffolds were assessed for their relative performance in simulated synovial fluids of 1 and 4 mg/mL sodium hyaluronate with application of model-free analysis with Biomaterials Enhanced Simulation Test (BEST). Pure PLA scaffold was used as a control. The BEST results were compared to the results of a prior in vivo study with rhCol-PLA. Collectively the data indicated that a successful articular cartilage repair require lower stiffness of the scaffold compared to surrounding cartilage yet matching the strain compliance both in static and dynamic conditions. This ensures an optimal combination of load transfer and effective oscillatory nutrients supply to the cells. The results encourage further development of intelligent scaffold structures for optimal articular cartilage repair rather than simply trying to imitate the respective original tissue.
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