In Vitro Evaluation of Calcium Phosphate Bone Cement Composite Hydrogel Beads of Cross-Linked Gelatin-Alginate with Gentamicin-Impregnated Porous Scaffold

Abstract

Calcium phosphate bone cement (CPC) is in the form of a paste, and its special advantage is that it can repair small and complex bone defects. In the case of open wounds, tissue debridement is necessary before tissue repair and the subsequent control of wound infection; therefore, CPC composite hydrogel beads containing antibiotics provide an excellent option to fill bone defects and deliver antibiotics locally for a long period. In this study, CPC was composited with the millimeter-sized spherical beads of cross-linked gelatin–alginate hydrogels at the different ratios of 0 (control), 12.5, 25, and 50 vol.%. The hydrogel was impregnated with gentamicin and characterized before compositing with CPC. The physicochemical properties, gentamicin release, antibacterial activity, biocompatibility, and mineralization of the CPC/hydrogel composites were characterized. The compressive strength of the CPC/hydrogel composites gradually decreased as the hydrogel content increased, and the compressive strength of composites containing gentamicin had the largest decrease. The working time and setting time of each group can be adjusted to 8 and 16 min, respectively, using a hardening solution to make the composite suitable for clinical use. The release of gentamicin before the hydrogel beads was composited with CPC varied greatly with immersion time. However, a stable controlled release effect was obtained in the CPC/gentamicin-impregnated hydrogel composite. The 50 vol.% hydrogel/CPC composite had the best antibacterial effect and no cytotoxicity but had reduced cell mineralization. Therefore, the optimal hydrogel beads content can be 25 vol.% to obtain a CPC/gentamicin-impregnated hydrogel composite with adequate strength, antibacterial activity, and bio-reactivity. This CPC/hydrogel containing gentamicin is expected to be used in clinical surgery in the future to accelerate bone regeneration and prevent prosthesis infection after surgery.

Biodegradable Hydrogel Beads Combined with Calcium Phosphate Bone Cement for Bone Repair: In Vitro and In Vivo Characterization

“…Although the CPC used in the present study has the same composition as the CPC used in other studies, differences still exist in terms of the molar ratio and surface treatment [ 15 , 35 ]. Our previous research showed that CPC-only developed in-house has the powerful ability to enhance cell attachment and osteogenic differentiation; therefore, the C/0.25 composite cannot positively affect in vitro proliferation and osteogenic function [ 29 ]. Furthermore, in the present study, 2–3 mm gelatin particles were directly added to the CPC matrix to provide an exposed template for creating submeter pores for cells (and not to verify the nucleation sites of nanoapatite), and this may be the cause of the difference in D1 cell culture performance [ 40 ].…”

“…Porous spheres were fabricated through solvent casting and particulate leaching and the detailed procedures followed our previously described methods [ 29 ]. A colloidal suspension was prepared by mixing sodium alginate and gelatin at a w/w ratio of 1:4, heating to 50 °C, and suspending the mixture in 10 mL of deionized distilled (DD) water.…”

“…Therefore, to improve the shortcoming of insufficient pores for tissue ingrowth, a compromise strategy is to composite biodegradable hydrogels, such as alginate, gelatin, alginate/chitosan, hyaluronic acid, and silk fibroin protein, as a filler in CPC matrix [ 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Studies have pointed out that the addition of hydrogel particles after implantation can be used as a carrier, which means that the hydrogel can protect the carrier factor from the hardening mechanism of CPC for a certain time [ 26 , 29 ]. In addition, the degraded hydrogel after clinical surgery can form pores in situ.…”

“…These holes can enhance blood vessels to grow inward, promote the transport of progenitor cells, and accelerate tissue healing [ 25 ]. According to our previous study [ 29 ], CPC composite hydrogel beads show controlled release of antibiotics, and the optimal content of hydrogel beads can be 25 vol.%, which has sufficient strength, antibacterial activity, and bio-reactivity. Continuing the previous research results, in this study, we selected 25 vol.% hydrogel beads to verify the in vitro and in vivo characteristics of the hydrogel beads/CPC composite.…”

Engineered bone cement trigger bone defect regeneration

“…Although the incidence of these adverse reactions is low, researchers still need to improve the setting properties of bone cement. The addition of natural organic substances such as alginate, chitosan, and gelatin to bone cement can improve the toughness, mechanical strength, and porosity of bone cement, thereby enhancing the ability of bone cement to induce bone regeneration and reducing its sequelae (Liu et al, 2021a;Wu et al, 2021). New bone formation is mainly caused by the joint action of osteoblasts, osteoclasts, and extracellular matrix at the site of injury (Katsimbri, 2017).…”