Effect of temporal onsets of mechanical loading on bone formation inside a tissue engineering scaffold combined with cell therapy

Abstract

Several approaches to combine bone substitutes with biomolecules, cells or mechanical loading have been explored as an alternative to the limitation and risk-related bone auto- and allo-grafts. In particular, human bone progenitor cells seeded in porous poly(L-lactic acid)/tricalcium phosphate scaffolds have shown promising results. Furthermore, the application of mechanical loading has long been known to be a key player in the regulation of bone architecture and mechanical properties. Several in vivo studies have pointed out the importance of its temporal offset. When an early mechanical loading was applied a few days after scaffold implantation, it was ineffective on bone formation, whereas a delayed mechanical loading of several weeks was beneficial for bone tissue regeneration. No information is reported to date on the effectiveness of applying a mechanical loading in vivo on cell-seeded scaffold with respect to bone formation in a bone site. In our study, we were interested in human bone progenitor cells due to their low immunogenicity, sensitivity to mechanical loading and capacity to differentiate into osteogenic human bone progenitor cells. The latest capacity allowed us to test two different bone cell fates originating from the same cell type. Therefore, the general aim of this study was to assess the outcome on bone formation when human bone progenitor cells or pre-differentiated osteogenic human bone progenitor cells are combined with early and delayed mechanical loading inside bone tissue engineering scaffolds. Scaffolds without cells, named cell-free scaffold, were used as control. Surprisingly, we found that (1) the optimal solution for bone formation is the combination of cell-free scaffolds and delayed mechanical loading and that (2) the timing of the mechanical application is crucial and dependent on the cell type inside the implanted scaffolds.

Exercise Promotes the Osteoinduction of HA/β-TCP Biomaterials via the Wnt Signaling Pathway

“…Research suggests that this process involves a link between inflammation and ectopic new bone formation: Activation of the canonical Wnt/β-catenin pathway and the non-canonical Wnt/PKCδ pathway is involved in inflammation-induced osteogenesis [22]. The process of osteoinduction is always accompanied by inflammation which was caused by surgical trauma, and the inflammation can activate endothelial cells and vascular endothelial growth factor (VEGF), etc., these cells and cytokines were usually used to be seed cells and osteogenic biomolecules in bone tissue engineering [23,24]. Our results show high levels of inflammation in the week following transplantation.…”

Application of subject-specific adaptive mechanical loading for bone healing in a mouse tail vertebral defect

“…This aspect is more important in the case of bone healing, where multiple overlapping phases exist. Early loading from two days onwards has been reported less effective than delayed loading at two weeks 37 . However, it has also been reported that early cyclic loading may increase oxygen transport to the defect region 38 , promoting the longer term regeneration response.…”

Banking Progenitor Cells for Hippiatric Regenerative Medicine: Optimized Establishment of Safe and Consistent Cell Sources for Standardized Veterinary Therapeutic Protocols

“…As was previously demonstrated in human translational medicine, simultaneous isolation of various fetal progenitor cell types from one organ donation enable highly efficient research and therapeutic development in all major aspects of musculoskeletal cell therapies [45,53,56,59,60,63]. Such knowledge and experience were extrapolated to veterinary therapeutic research, as immune privilege of progenitor cells potentially allows for safe xenogeneic…”

“…Wound healing rates after progenitor cell applications have been shown to be relatively more important and prompt with little scar tissue formation and an absence of immunogenic or tumorigenic properties has been documented [43,[45][46][47][48]. Generalized and tissue-specific application of progenitor cell technology to musculoskeletal regenerative medicine has effectively been a local driver of translational biomedical research and is currently being evaluated for human and veterinary patients in Switzerland [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65]. The present work is consistent with the One Health Initiative (www.onehealthinitiative.com), an approach of integrative medicotherapeutic development under which veterinary medicine can benefit from human medicine and vice versa.…”