Preparation and property of a novel bone graft composite consisting of rhBMP-2 loaded PLGA microspheres and calcium phosphate cement

Abstract

Calcium phosphate cement (CPC) is a highly promising bone substitute and an excellent carrier for delivering growth factors. Yet, the lack of macro-porosity and osteoinductive ability, limit its use. This study is aimed at developing a novel biodegradable biomaterial for bone repair with both highly osteoconductive and osteoinductive properties. RhBMP-2 loaded PLGA microspheres were incorporated into rhBMP-2/CPC for macropores for bone ingrowth. The compressive strength, crystallinity, microscopic structure, and bioactivity of the composites were investigated. The results showed that with the incorporation of rhBMP-2 loaded PLGA microspheres, the compressive strength was decreased from (29.48+/-6.42) MPa to (8.26+/-3.58) MPa. X-ray diffraction revealed that the crystallinity pattern of HA formed by CPC had no significant change. Inside the composite, the microspheres distributed homogeneously and contacted intimately with the HA matrix, as observed by scanning electron microscopy (SEM). When the PLGA microspheres dissolved after having been emerged in PBS for 56 days, macropores were created within the CPC. The rhBMP-2/PLGA/CPC composite, showing a 4.9% initial release of rhBMP-2 in 24 h, followed by a prolonged release for 28 days, should have a greater amount of rhBMP-2 released compared to the CPC delivery system. When rabbit marrow stromal cells were cocultured with the composite, the alkaline phosphatase (ALP) and osteocalcin (OC) showed a dose response to the rhBMP-2 released from the composite, indicating that the activity of rhBMP-2 was retained. This study shows that the new composite reveals more rhBMP-2 release and osteogenic activity. This novel BMP/PLGA/CPC composite could be a promising synthetic bone graft in craniofacial and orthopedic repairs.

Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

“…Release of rhBMP-2/GM/CPC was characterized by an initial burst release followed by a period of sustained release, as reported previously [5]. rhBMP-2/PLGA/CPC exhibited the same pattern [4,24,25]. Therefore, we consider this pattern typical in the composite with microspheres and CPC.…”

“…The differences might be attributable to the lower degree of cross-linking in our GMs compared with those of Habraken et al [5,6] and Li et al [10]; thus, the degradation period of our GMs was shorter than that of Habraken et al, and the drug release from the composite with microspheres and CPC apparently was accelerated by the faster degradation of microspheres [5,10]. The mean amount of rhBMP-2 release from our rhBMP-2/GM/CPC was 38% after 28 days, and greater than the mean of 15% to 33% of rhBMP-2/PLGA/CPC reported previously [4,25]. Greater rhBMP-2 release in our composite also resulted from the faster degradation of the GM (4 weeks) compared with PLGA (8-12 weeks) [7,10,12,27].…”

“…Previous reports have suggested greater release of growth factors when composite bone graft substitutes contain PLGA microspheres and CPCs [4,24,25]. Sustained release of BMPs can accelerate bone healing in osteoporosis [3,23].…”

“…Li, X. Liu (&), X. Liu, B. Ge Orthopedic Trauma Institute of CPLA, Lanzhou General Hospital of CPLA, 333 Bing-he-nan Road, Lanzhou 730050 Gansu Province, People's Republic of China e-mail: xingyanliulz@yahoo.com.cn rate of the factor and the long degradation period [4,28]. Poly[D,L-lactic-co-glycolic] acid (PLGA) microspheres loaded with rhBMP-2 and incorporated into CPC [4,24,25] may provide an alternative bone substitute. The cumulative release of rhBMP-2 from rhBMP-2/PLGA/CPC is approximately 14.5% to 32.5% after 28 days, and the activity of rhBMP-2 is retained [4,24,25].…”

“…Poly[D,L-lactic-co-glycolic] acid (PLGA) microspheres loaded with rhBMP-2 and incorporated into CPC [4,24,25] may provide an alternative bone substitute. The cumulative release of rhBMP-2 from rhBMP-2/PLGA/CPC is approximately 14.5% to 32.5% after 28 days, and the activity of rhBMP-2 is retained [4,24,25]. In addition, with degradation of the microspheres, macropores are produced in the composite, and resorption of the composite can be enhanced [27].…”