Long-term biological performance of injectable and degradable calcium phosphate cement

Abstract

Enhancing degradation of poorly degrading injectable calcium phosphate (CaP) cements (CPCs) can be achieved by adding poly(lactic-co-glycolic acid) (PLGA) microparticles, generating porosity after polymer degradation. CPC-PLGA has proven to be biodegradable, although its long-term biological performance is still unknown. Optimization of injectability could be achieved via addition of carboxymethyl cellulose (CMC). Here, we evaluated the long-term in vivo performance of CPC-PLGA with or without the lubricant CMC in comparison to the devitalized bovine bone mineral (DBBM) predicate device Bio-Oss. Rabbit femoral bone defects were injected with a CPC-formulation or filled with Bio-Oss granules. Samples were retrieved at 6 and 26 weeks. Material degradation for Bio-Oss was marginal, starting with 57% material remnants at implantation, 49% at 6 weeks, and 35% at 26 weeks, respectively. In contrast, CPC-PLGA and CPC-PLGA-CMC showed significant material degradation, starting with 100% material remnants at implantation, 56 and 78% at 6 weeks, and 8 and 21% at 26 weeks. Bone formation showed to be rapid for Bio-Oss, with 24% at 6 weeks, and a similar value (27%) at 26 weeks. Both CPC-PLGA and CPC-PLGA-CMC showed a continuous temporal increase in bone formation, with 13 and 6% at 6 weeks, and 44 and 32% at 26 weeks. This study showed that CPC-PLGA induces favorable bone responses with >90% degradation and >40% new bone formation after an implantation period of 26 weeks.

Effect of modified compound calcium phosphate cement on the differentiation and osteogenesis of bone mesenchymal stem cells

“…Modified Urist method can properly preserve and release BMP cytokines [7, 8]. BMP is capable of inducing cells with osteogenic potential to differentiate into osteoblasts.…”

Sterilization effects on the handling and degradation properties of calcium phosphate cements containing poly (D,L‐lactic‐co‐glycolic acid) porogens and carboxymethyl cellulose

“…As CPCs first form into a paste, they can be molded into arbitrarily shaped bone defect sites and set under physiological conditions, which enables them to be utilized in minimally invasive surgical procedures . These characteristic handling and biological properties have prompted CPCs to garner much attention in the dental and orthopedic field as an attractive alternative to other conventional bone substitute materials . Moreover, CPCs do not exhibit many of the complications associated with auto‐ and allografts such as donor site morbidity and chronic pain, surgical harvesting, limited availability, and risk of disease transfer and/or infection .…”

“…These characteristic handling and biological properties have prompted CPCs to garner much attention in the dental and orthopedic field as an attractive alternative to other conventional bone substitute materials . Moreover, CPCs do not exhibit many of the complications associated with auto‐ and allografts such as donor site morbidity and chronic pain, surgical harvesting, limited availability, and risk of disease transfer and/or infection . Nevertheless, the clinical applicability of CPCs has remained limited due to two factors: (i) poor degradability due to a lack of interconnected macroporosity to allow for vascularization and bone tissue ingrowth and (ii) poor cohesion and washout resistance, which is especially important when considering their indications for skeletal sites where perfusion is high, such as the spine .…”

“…Calcium phosphate cements are capable of degrading by either active or passive resorption. Active resorption is mediated by the cellular activity of osteoclasts during bone remodeling, while passive resorption is dictated by the chemical solubility of the CPC matrix . However, the rate of resorption of apatite‐forming CPCs is slower than the rate of new bone formation, which limits the potential for new bone to regenerate due to the lack of porosity to allow for bone ingrowth and vascularization .…”

Multimodal porogen platforms for calcium phosphate cement degradation

“…10 Previous work has shown that chemical characteristics of PLGA (i.e., acid-terminated or end-capped), porogen type (i.e., dense or hollow), and size all influence the degradation of CPC-PLGA composites. 13 Although CPC-PLGA demonstrated superiority regarding material degradation and bone formation after a prolonged implantation period of 6 months, initial bone formation was delayed. 12 These pores create macroporosity within the ceramic CPC matrix, which allows for fluid flow and tissue ingrowth, especially when the created pores are interconnected.…”