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

Abstract

Background The capacity for bone healing reportedly is limited in osteoporosis with a less than ideal environment for healing of bone grafts. We therefore developed a composite bone substitute with rhBMP-2 loaded gelatin microsphere (GM) and calcium phosphate cement (CPC) to use in osteoporosis. Questions/purposes We asked whether (1) controlled release of rhBMP-2 could be improved in this composite bone substitute and (2) increasing factors released from the bone substitute could accelerate osteoporotic bone healing. Methods We soaked rhBMP-2/GM/CPC and rhBMP-2/ CPC composites in simulated body fluid for 28 days and then determined the amount of rhBMP-2 released. Both composites were implanted in bone defects of osteoporotic goats and left in place for 45 and 140 days; the specimens then were evaluated mechanically (pushout test) and morphologically (CT scanning, histology). Results The in vitro study showed the new composite released more rhBMP-2 compared with rhBMP-2/CPC. CT showed the defects healed more quickly with new grafts. The bone mineralization rate was greater in rhBMP-2/GM/ CPC than in rhBMP-2/CPC after 45 days of implantation and the pushout test was stronger after 45 and 140 days of implantation. Conclusions The new graft composite released more loaded factors and appeared to repair osteoporotic bone defects. Clinical Relevance These preliminary data suggest the new composite can be used as a bone substitute to accelerate healing of fractures and bone defects in osteoporosis.

Self-Setting Calcium Orthophosphate Formulations: Cements, Concretes, Pastes and Putties

“…To conclude this part, one should stress, that the most promising direction of the future developments of self-setting calcium orthophosphate formulations is obviously seen in their functionalization by incorporation or impregnation of various hormones, growth factors, drugs, other bioorganic compounds, as well as incorporation of living cells and/or other tiny biological objects [605][606][607][608][609][610][611][612][613][614][615][616]. For example, silk fibroin can regular the mineralization process and bond with HA to form fibroin/HA nanodimensional biocomposites with increased gelation properties and, thus, it can be used as an additive to improve cohesion of calcium orthophosphate cements and decrease a risk of cardiovascular complications in its application in veterbroplasty and kyphoplasty [612].…”

Blooming gelatin: an individual additive for enhancing nanoapatite precipitation, physical properties, and osteoblastic responses of nanostructured macroporous calcium phosphate bone cements

“…The promising effects of gelatin on osteointegration of threedimensional gelatin-coated hydroxyapatite (HA) foams have been described by Gil-Albarova et al 8 Gelatin microspheres as drug carriers were also incorporated into CPC to enhance bone formation in osteoporosis. 9 Teotia et al synthesized injectable bone cement comprising a mixture of calcium sulfate, HA, and gelatin and proved that gelatin can enhance cell proliferation and ALP activity of human osteosarcoma cells, in this system. 10 Habraken et al 11 improved the handling properties and biodegradation of CPCs using gelatin microspheres.…”

Minimally Invasive Subpericranial Model: Can It Be Used to Study Bone Substitutes?

“…Since the total injected volume was 1000 mm 3 , and since the outcome was very similar to a semi hemisphere, measurements were conducted by the formula: Figure 1). The microscopic measurements consisted of a morphometric analysis of the volume fraction (V v ) of the following parameters: newly formed bone, newly formed blood vessels, residual BVF grafting material; chronic inflammation.…”

“…However, the procedure may be associated with soft-tissue complications, including unaesthetic surgical scars and donor-site morbidity. Although synthetic bone fillers offer a potential alternative to autogenous bone grafts, extensive efforts to develop an ideal alloplastic bone substitute have so far been unsuccessful [1][2][3][4]. Given the complex structure of the craniofacial skeleton, the graft material must ideally be biocompatible and resilient, fast-setting, easily inserted, and able to be molded and integrate with surrounding bone in order to mimic the original bone structure [5][6][7][8].…”