Manufacture of Soft-Hard Implants from Electrospun Filaments Embedded in 3D Printed Structures.

Rotator cuff tendon tears are common injuries of the musculoskeletal system that often require surgical repair. However, re-tearing following repair is a significant clinical problem, with a failure rate of up to 40%, notably at the transition from bone to tendon. The development of biphasic materials consisting of soft and hard components, which can mimic this interface, is therefore promising. Here, a simple manufacturing approach is proposed that combines electrospun filaments and 3D printing to achieve scaffolds made of a soft polydioxanone cuff embedded in a porous polycaprolactone block. The insertion area of the cuff is based on the supraspinatus tendon footprint and the size of the cuff is scaled up from 9 to 270 electrospun filaments to reach a clinically relevant strength of 227N on average. The biological evaluation shows that the biphasic scaffold components are noncytotoxic, and that tendon and bone cells can be grown on the cuff and block, respectively. Overall, these results indicate that combining electrospinning and 3D printing is a feasible and promising approach to create soft-to-hard biphasic scaffolds that can improve the outcomes of rotator cuff repair.

Sequential growth factor exposure of human Ad-MSCs improves chondrogenic differentiation in an osteochondral biphasic implant.

Joint cartilage damage affects 10-12% of the world's population. Medical treatments improve the short-term quality of life of affected individuals but lack a long-term effect due to injury progression into fibrocartilage. The use of mesenchymal stem cells (MSCs) is one of the most promising strategies for tissue regeneration due to their ability to be isolated, expanded and differentiated into metabolically active chondrocytes to achieve long-term restoration. For this purpose, human adipose-derived MSCs (Ad-MSCs) were isolated from lipectomy and grown in xeno-free conditions. To establish the best differentiation potential towards a stable chondrocyte phenotype, isolated Ad-MSCs were sequentially exposed to five differentiation schemes of growth factors in previously designed three-dimensional biphasic scaffolds with incorporation of a decellularized cartilage matrix as a bioactive ingredient, silk fibroin and bone matrix, to generate a system capable of being loaded with pre-differentiated Ad-MSCs, to be used as a clinical implant in cartilage lesions for tissue regeneration. Chondrogenic and osteogenic markers were analyzed by reverse transcription-quantitative PCR and cartilage matrix generation by histology techniques at different time points over 40 days. All groups had an increased expression of chondrogenic markers; however, the use of fibroblast growth factor 2 (10 ng/ml) followed by a combination of insulin-like growth factor 1 (100 ng/ml)/TGFß1 (10 ng/ml) and a final step of exposure to TGFß1 alone (10 ng/ml) resulted in the most optimal chondrogenic signature towards chondrocyte differentiation and the lowest levels of osteogenic expression, while maintaining stable collagen matrix deposition until day 33. This encourages their possible use in osteochondral lesions, with appropriate properties for use in clinical patients.