The kinetics and mechanism of bone morphogenetic protein 2 release from calcium phosphate‐based implant‐coatings

Abstract

Biomimetically deposited calcium phosphate-based coatings of prostheses can serve as a vehicle for the targeted delivery of growth factors to the local implant environment. Based on indirect evidence in previous studies we hypothesize that such agents are liberated gradually from the coating via a cell-mediated degradation. In the present study, we tested this hypothesis by investigating the release mechanism and its kinetics by use of a radiolabeled osteogenic agent ( I-BMP-2) under conditions in which native cell populations with a coating-degradative potential were either absent or present. The release of I-BMP-2 was monitored for 5 weeks, either in vitro or after implantation at an ectopic (subcutaneous) site in rats in vivo. Only from implants that bore a coating-incorporated depot of bone morphogenetic protein 2 (BMP-2) was the agent released slowly and steadily over 5 weeks, that is, 50% of the loaded dose was liberated in vivo (5 to 10% weekly), as against 14.6% in vitro (less than 1% weekly). The coatings bearing an incorporated depot of BMP-2 underwent significant cell-mediated degradation, whereas under cell-free conditions no degradation occurred, and the spontaneous release of BMP-2 was negligible. Our findings confirm this carrier system to be a suitable vehicle for the sustained and cell-mediated delivery of BMP-2. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2363-2371, 2018.

A dual functional bone‐defect‐filling material with sequential antibacterial and osteoinductive properties for infected bone defect repair

“…However, due to the similarity in the physicochemical properties of BMP2 and FITC‐BSA or rhodamine B and HACC, this alternative cost‐effective method at least reflects the release pattern of the drug of interest. Moreover, in our recent study, the release pattern of BMP2 from the BMP2‐BioCaP complex in vitro was similar to the release pattern of FITC‐BSA form HACC/FITC‐BSA‐BioCaP in this study (Liu, Schouten, et al, ). In this study, around 20% BSA was released from day 5 to day 30, the remaining 80% drug was still entrapped in the BioCaP.…”

“…To function as an effective osteoinductive agent, BMP2 needs to be released slowly and continuously at low concentrations (Hunziker et al, ). Based on this theory, we developed BMP2‐BioCaP granules (Liu, Wu, et al, ), in which BMP2 was internally incorporated into the BioCaP granules and gives slow and sustained release in vitro and in vivo (Liu, Schouten, et al, ).…”

Periodontal regeneration using bone morphogenetic protein 2 incorporated biomimetic calcium phosphate in conjunction with barrier membrane: A pre‐clinical study in dogs

“…As described in our previous study (Liu et al, 2018), only 50% of BMP-2 was released after 5 weeks. We can speculate that there would be more regenerated cementum if we extended the experimental period.…”

Biocompatible PLGA-Mesoporous Silicon Microspheres for the Controlled Release of BMP-2 for Bone Augmentation

“…Clinically this has translated in to the development of multiple complications [1,10]. Currently formulated BMP devices must be used at high concentrations resulting in problems with protein release timing stability, and need for accessory factors [11,12]. Additionally, the bone regenerative process under these conditions is very different from the normal physiologic processes in normal bone healing in which multiple BMPs and other growth factors are present in overlapping temporal patterns [13,14].…”

“…Bone morphogenetic protein-2 (BMP-2) is a transforming growth factor known to play a key role in the development and repair of bone and cartilage [5]. Initially, it appeared to provide an ideal solution [6][7][8] to enhance bone growth but as its clinical use has expanded, multiple complications associated with BMP-2 use have come to light including local wound problems, chemical radiculitis, bony overgrowth into the canal or foramen, osteoclast activation with associated bony resorption and device displacement, and, possibly, cancer when used at very high doses in an off-label manner [1,[9][10][11]. It is thought these complications were associated with the uncontrolled release and systemic distribution of supraphysiologic doses of this potent growth factor [1,12].…”