Bone Morphogenic Protein 2-Loaded Porous Silicon Carriers for Osteoinductive Implants

Abstract

Bone morphogenetic proteins (BMPs) are probably the most important growth factors in bone formation and healing. However, the utilization of BMPs in clinical applications is mainly limited due to the protein poor solubility at physiological pH, rapid clearance and relatively short biological half-life. Herein, we develop degradable porous silicon (PSi)-based carriers for sustained delivery of BMP-2. Two different loading approaches are examined, physical adsorption and covalent conjugation, and their effect on the protein loading and release rate is thoroughly studied. The entrapment of the protein within the PSi nanostructures preserved its bioactivity for inducing osteogenic differentiation of rabbit bone marrow mesenchymal stems cells (BM-MSCs). BM-MSCs cultured with the BMP-2 loaded PSi carriers exhibit a relatively high alkaline phosphatase (ALP) activity. We also demonstrate that exposure of MSCs to empty PSi (no protein) carriers generates some extent of differentiation due to the ability of the carrier’s degradation products to induce osteoblast differentiation. Finally, we demonstrate the integration of these promising BMP-2 carriers within a 3D-printed patient-specific implant, constructed of poly(caprolactone) (PCL), as a potential bone graft for critical size bone defects.

Magnesium hydroxide-incorporated PLGA composite attenuates inflammation and promotes BMP2-induced bone formation in spinal fusion

“… 38 As mentioned previously, many approaches are available to overcome the disadvantages of BMP2 and improve both its safety and therapeutic efficacy by utilizing different carrier systems. 5 , 10 – 16 , 38 The release profile of BMP2 from PLGA/BMP2 and PLGA/MH/BMP2 exhibited an initial burst release followed by slow release for up to 8 weeks ( Figure 3(b) and ( c )). Interestingly, the PLGA/MH/BMP2 film indicated a more significant release of BMP2 when compared to PLGA/BMP2 film.…”

“…The carriers used for delivery are made of metals, ceramics, polymers, and composites. 5,[10][11][12][13][14][15][16][17][18][19] Poly(lactic-co-glycolic acid) (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. 16,18,20 Many PLGA delivery systems for BMP2 have shown promise for bone repair.…”

“…Many carriers and delivery systems comprised of different materials have been investigated to maintain the controlled release and improve the safety and therapeutic efficacy of BMP2. 5 , 10 – 16 The delivery systems come in the form of hydrogels, microspheres, nanoparticles, and fibers. The carriers used for delivery are made of metals, ceramics, polymers, and composites.…”

3D Printing and Nanotechnology: A Multiscale Alliance in Personalized Medicine

“…According to the authors, porous‐silicon‐based delivery systems loaded with osteoinductive growth factors for local administration and inserted in biodegradable implants create great opportunities for bone regeneration therapies. [ 123 ]…”

Drug Delivery Applications of Three-Dimensional Printed (3DP) Mesoporous Scaffolds

“…Fish hydrogel-based mesoporous strontium-doped calcium silicate scaffolds were proved to be efficient BMP-2 carriers for in vitro human Wharton jelly mesenchymal stem cell differentiation [ 69 ]. Customized 3D-printed osteoinductive implants were realized integrating porous silicon BMP-2 carriers within a 3D-printed PCL patient-specific implant [ 70 ]. FDM 3D MesoCS scaffolds combined with PCL were presented as odontoinductive biomaterial with efficient BMP-2 delivery capability [ 71 ].…”