Surface delivery of tunable doses of BMP-2 from an adaptable polymeric scaffold induces volumetric bone regeneration

Abstract

The rapid and effective bone regeneration of large non-healing defects remains challenging. Bioactive proteins, such as bone morphogenetic protein (BMP)-2, are proved their osteoinductivity, but their clinical use is currently limited to collagen as biomaterial. Being able to deliver BMP-2 from any other biomaterial would broaden its clinical use. This work presents a novel means for repairing a critical size volumetric bone femoral defect in the rat by combining a osteoinductive surface coating (2D) to a polymeric scaffold (3D hollow tube) made of commercially-available PLGA. Using a polyelectrolyte film as BMP-2 carrier, we tune the amount of BMP-2 loaded in and released from the polyelectrolyte film coating over a large extent by controlling the film crosslinking level and initial concentration of BMP-2 in solution. Using microcomputed tomography and quantitative analysis of the regenerated bone growth kinetics, we show that the amount of newly formed bone and kinetics can be modulated: an effective and fast repair was obtained in 1-2 weeks in the best conditions, including complete defect bridging, formation of vascularized and mineralized bone tissue. Histological staining and high-resolution computed tomography revealed the presence of bone regeneration inside and around the tube with spatially distinct organization for trabecular-like and cortical bones. The amount of cortical bone and its thickness increased with the BMP-2 dose. In view of the recent developments in additive manufacturing techniques, this surface-coating technology may be applied in combination with various types of polymeric or metallic scaffolds to offer new perspectives of bone regeneration in personalized medicine.

Sequential sequestrations increase the incorporation and retention of multiple growth factors in mineralized collagen scaffolds

“…Incorporating BMP2 into scaffolds for bone repair is very common and has shown to improve osteogenesis in multiple systems [36][37][38][39][40][41][42] . However, the need for doses of soluble BMP2 larger than what's normally found in the body has led to complications such as abnormal bone formation 43,44 .…”

Polydopamine-assisted functionalization of heparin and vancomycin onto microarc-oxidized 3D printed porous Ti6Al4V for improved hemocompatibility, osteogenic and anti-infection potencies

“…Recently, advanced orthopedic porous implants by 3D printing targeted at functional bone defect restoration have become a hot research topic; however, the focus is mainly on endowing them with osteointegration functions rather than antimicrobial activities [13,48,49]. To impart antimicrobial coatings onto orthopedic implants is an efficient and versatile approach.…”

Bioactive Membrane Immobilized with Lactoferrin for Modulation of Bone Regeneration and Inflammation

“…5,6 For example, poly(lactic-co-glycolic acid) nanofibers immobilized with bone morphogenetic protein 2 enhanced in vivo bone regeneration by two times compared with that of unmodified fibers when they were transplanted into criticalsized femoral bone defects in rats. 7 Although many of the methods succeeded in enhancing bone regeneration, they often reported serious inflammatory reactions at the tissue interface during the surgical process, and thereby, reduced bone regeneration. 8,9 The implanted membranes initiate the immune system by inducing the expression of proinflammatory cytokines from macrophages such as tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b), which generate local inflammation, resulting in the inhibition of the osteoblastic differentiation of stem cells and delayed bone formation.…”