Application of alginate microbeads as a carrier of bone morphogenetic protein‐2 for bone regeneration

Abstract

Bone morphogenetic protein-2 (BMP-2) is commonly used to enhance bone regeneration. The potential of BMP-2 for bone regeneration varies according to the concentration and release kinetics on the implanted site. Therefore, it is important to determine appropriate carriers of BMP-2. However, no optimal delivery vehicles have been identified. In the present study, we used alginate microbeads as a delivery vehicle for BMP-2. Alginate microbeads can be implanted onto the disease site through surgery or injection. The objective of this study was to evaluate that the osteoinductive properties of BMP-2 are effective in alginate microbeads as a carrier. In this study, the release kinetics of BMP-2 in alginate microbeads was evaluated using an enzyme-linked immunosorbent assay. BMP-2 released from alginate microbeads induced high alkaline phosphatase activity in canine adipose tissue-derived mesenchymal stem cells. Injection of alginate microbeads with BMP-2 into mouse subcutaneous tissue, as well as surgical implantation into the 5-mm circular calvarial defects in rats, was conducted and the results showed extensive new bone formation. In conclusion, alginate microbeads can be utilized as an effective BMP-2 delivery vehicle for use in orthopedic surgery and as an injectable vehicle for a minimally invasive therapy. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.

Surgical Ectrodactyly Repair Using Limb-lengthening and Bone Tissue Engineering Techniques in a Toy Dog Breed

“…In recent decades, bone tissue engineering techniques, such as limb salvage procedures, have been used to treat critical-sized bone defects in veterinary patients (17,(22)(23)(24). Some studies have demonstrated the effectiveness of BMP-2 alone, or in combination with scaffolds, in inducing bone formation and healing of long bone defects (17,19,(22)(23)(24)(25). In the present case, an implant failure occurred 3 months after arthrodesis and the patient received an implant replacement, which also failed 4 months after application.…”

“…According to an in vivo study in a rat carvarial defect model, the use of alginate microbeads as carriers of BMP-2, results in a burst release pattern within the first few days, followed by a long-term sustained release pattern. Furthermore, the same study also found that rats implanted with BMP-2loaded alginate microbeads showed more effective bone formation, when compared to other experimental groups (19). Collagen sponges, which show a sustained release pattern, are also routinely used as carriers of BMP-2.…”

“…A mini circular ESF (IMEX) was applied to the proximal and distal segments of the fracture with four 1.0 mm K-wires for the proximal segment and two 1.0 mm K-wires for the distal segment. A mixture of bone grafts composed of cancellous chips (2~4 mm, Veterinary Tissue Bank Ltd.) and alginate microbeads loaded with rhBMP-2 (0.2 mg, NOVOSIS), as previously described (19), was applied to the defective area. A collagen sponge [1×2 cm; Lyostypt ® (B-Braun, Barcelona, Spain)] wet with rhBMP-2 (0.05 mg, NOVOSIS), was used to encompass the surgical area.…”

Bone Regeneration by Low-dose Recombinant Human Bone Morphogenetic Protein-2 Carried on Octacalcium Phosphate Collagen Composite

“…and sustained released of BMP-2 is needed 19) . The carrier must be nontoxic, noncarcinogenic, nonantigenic, proinflammatory, and preferably biodegradable and moldable 23) .…”

“…OCP/Col has also been shown to be both safe and efficacious in human tooth extraction sockets, cystic cavities, and maxillary sinus floor elevation [15][16][17][18] . BMP-2 is known to absorb calcium phosphate and Correspondence to: Dr. Kei-ichiro Miura, Department of Regenerative Oral Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan, 1-7-1, Sakamoto, Nagasaki 852-8588, Japan; Phone: +810958197704; E-mail: kei.miura.e.mail@gmail.com also collagen 19,20) . Therefore, we propose that OCP/Col could be a superior carrier for rhBMP-2 to minimize the required rhBMP-2 dose.…”