Induction of the early inflammatory‐mediated cellular responses of fracture healing in vitro using platelet releasate‐containing alginate/CaPO₄ biomaterials for early osteoarthritis prevention

Abstract

A significant gap exists in our understanding of subchondral and cancellous bone changes that may regulate osteoarthritis progression. Herein, we complement our prior osteochondrogenesis work with growth factor elution and monocyte and endothelial cell activation using two biomaterial formulations. The design of these biomaterials was inspired by the roles of a fracture hematoma, more specifically, the potential of significant cross-talk among cells and cellular factors that affect bone remodeling. Biomaterials, referred to herein as F1+ and F2+, are human concentrated platelet releasate-containing alginate/beta-tricalcium phosphate composites. F1+ has a higher calcium phosphate volume percentage and lower alginate polymer weight percent hydrogel versus F2+. The majority of releasate-derived platelet-derived growth factor eluted over 24 h for F1+ and 48 h for F2+, suggesting sustained release with an increase in alginate weight percentage. Simple monocyte and endothelial cell migration studies demonstrated 650% and 900% increases with F1+ eluate over medium alone, respectively. Induction of endothelial cell invasion over supplemented medium positive control was also shown for F2+ eluate (p = 0.03) with F1+ eluate being similar to the control. Monocyte transendothelial migration was increased over 300% and 400% for F1+ and F2+ eluates compared with medium alone, respectively. In addition, F1+ and F2+ eluates induced spontaneous endothelial tube formations similar to supplemented medium, demonstrating a well-formed network of capillary-like structures. This work demonstrated our biomaterial formulations ability to induce characteristics in vitro that parallel the in vivo behavior of fracture hematomas and potential to induce bone remodeling for the early treatment of osteoarthritic joints.

Hematoma-inspired alginate/platelet releasate/CaPO4 composite: initiation of the inflammatory-mediated response associated with fracture repair in vitro and ex vivo injection delivery

“…This work completes a series of in vitro experiments aimed at preempting the in vivo response of injectable in situ curing alginate/platelet releasate/CaPO 4 composites [13,22]. The current and prior findings advocate application of this system for use as cost efficient, robust bone graft substitutes.…”

“…The following work completes a series of in vitro experiments; prior investigations demonstrated biocompatibility and osteochondrogenic potential for the biocomposites using murine mesenchymal stem cells, angiogenic characteristics using human umbilical vein endothelial cells (HUVECs), and chemo/haptotactic abilities using HUVECs and an immortalized murine monocyte line (which, additionally, is used in the current study) [12][13][14]. While earlier findings are promising, neovascularization and activated immune cell-mediated resorption of damaged and irregular mineralized tissue and the bone graft substitute systems are also essential processes for osseous tissue rejuvenation.…”

Evaluation of Two Highly Porous Microcrystalline Biphasic Calcium Phosphate-Based Bone Grafts for Bone Regeneration: An Experimental Study in Rabbits

“…Using light microscopy, we made a comparative analysis of the distribution and activities of osteoblastic cells on biomaterials 30, 60, and 90 days after implantation. The present work takes a multimodal approach consisting of a study of the crystallinity, composition, and pore-volume, as well as compression testing, of this new material and its cellular biodegradation when used to fill critically sized bone defects in rabbit tibia, comparing its performance with those of a commercially available β-TCP graft material (Synergy Odontit ® ; Buenos Aires, Argentina) [43] and unfilled control defects.…”