Gelatin-Modified Bone Substitute with Bioactive Molecules Enhance Cellular Interactions and Bone Regeneration

Abstract

In this work, we have synthesized injectable bone cement incorporated with gelatin to enhance cellular interaction. Human osteosarcoma Saos-2 cells derived bone morphogenetic proteins (BMP's) and a bisphosphonate (zoledronic acid (0.2 mM)) were also incorporated to cement. In vitro studies conducted using Saos-2 demonstrated enhanced cell proliferation on gelatin (0.2%w/v) cement. The differentiation of C2C12 mouse myoblast cells into bone forming cells showed 6-fold increase in ALP levels on gelatin cement. Polymerase chain reaction (PCR) for bone biomarkers showed osteoinductive potential of gelatin cement. We investigated efficacy for local delivery of these bioactive molecules in enhancing bone substitution qualities of bone cements by implanting in 3.5 mm critical size defect in tibial metaphysis of wistar rats. The rats were sacrificed after 12 weeks and 16 weeks post implantation. X-ray, micro-CT, histology, and histomorphometry analysis were performed to check bone healing. The cement materials slowly resorbed from the defect site leaving HAP creating porous matrix providing surface for bone formation. The materials showed high biocompatibility and initial bridging was observed in all the animals but maximum bone formation was observed in animals implanted with cement incorporated with zoledronic acid followed by cement with BMP's compared to other groups.

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

“…Teotia et al synthesized injectable bone cement incorporated with gelatin as a bioactive molecule to improve cellular interaction. 10 Suarasan et al showed that coating gelatin on gold nanoparticles enhanced cell proliferation and osteoblasts differentiation with bone nodule formation. 24 Figure 11 represents the amount of ALP enzyme produced in the osteoblasts over a period of time.…”

“…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. The foaming capacity and handling properties of a gelatin-incorporated α-tricalcium phosphate-base CPC were recently evaluated by Montufar et al 12 The authors showed that gelatin additive improves the cohesion and injectability of the cement paste.…”

“…The RGD motifs can mediate cell attachment through interaction with integrin, a transmembrane receptor, which is a bridge for cell-cell and cell-extracellular matrix interactions. 10 These interactions would result in better cell responses and biocompatibility. The gelatin molecules can also produce improved cell responses indirectly through promoting effect on apatite precipitation.…”

3D printed TCP-based scaffold incorporating VEGF-loaded PLGA microspheres for craniofacial tissue engineering

“…In this case, biopolymers such as gelatin and alginate might be used both as the binder to facilitate the printing process and as the matrix to incorporate growth factor carriers. Gelatin, a natural polymer obtained from partial hydrolysis of collagen, provides Arg-Gly-Asp (RGD) motifs that can mediate cell attachment via interaction with integrin [30–32]. The sol-gel transition of gelatin can be exploited in 3D printing procedures.…”

Enhanced bone regeneration using an insulin-loaded nano-hydroxyapatite/collagen/PLGA composite scaffold

“…These scaffolds can regulate specific functions of bone marrow mesenchymal stem cells (BMSCs), including gene expression processes associated with cell growth and osteogenic differentiation. 1,2 Insulin has been increasingly accepted as an inducible factor for bone turnover and osteogenesis. BMSCs have been proved to express functional insulin receptors and respond to exogenous insulin by increasing proliferation rates, 3 alkaline phosphatase (ALP) production, 4 and collagen synthesis, 5 which is associated with the upregulation of PI3-K/Akt in cells.…”