No abstract

Hydroxyapatite (HA), especially in the form of HA nanoparticles (HANPs), has excellent bioactivity, biodegradability, and osteoconductivity and therefore has been widely used as a template or additives for drug delivery in clinical applications, such as dentistry and orthopedic repair. Due to the atomically anisotropic distribution on the preferred growth of HA crystals, especially the nanoscale rod-/whisker-like morphology, HA can generally be a good candidate for carrying a variety of substances. HA is biocompatible and suitable for medical applications, but most drugs carried by HANPs have an initial burst release. In the adsorption mechanism of HA as a carrier, specific surface area, pore size, and porosity are important factors that mainly affect the adsorption and release amounts. At present, many studies have developed HA as a drug carrier with targeted effect, porous structure, and high porosity. This review mainly discusses the influence of HA structures as a carrier on the adsorption and release of active molecules. It then focuses on the benefits and effects of different types of polymer-HA composites to re-examine the proteins/drugs carry and release behavior and related potential clinical applications. This literature survey can be divided into three main parts: 1. interaction and adsorption mechanism of HA and drugs; 2. advantages and application fields of HA/organic composites; 3. loading and drug release behavior of multifunctional HA composites in different environments. This work also presents the latest development and future prospects of HA as a drug carrier.

Although considerable achievements have been made in the field of regenerative medicine, since self-repair is not an advanced ability of articular cartilage, the regeneration of osteochondral defects is still a challenging problem in musculoskeletal diseases. Cartilage regeneration aims to design a scaffold with appropriate pore structure and biological and mechanical properties for the growth of chondrocytes. In this study, porous scaffolds made of gelatin, hyaluronic acid, alginate, and sucrose in different proportions of 2 g (SL2) and 4 g (SL4) were used as porogens in a leaching process. Sucrose with particle size ranges of 88–177 μm (Hμ) and 44–74 μm (SHμ) was added to the colloid, and the individually cross-linked hydrogel scaffolds with controllable pore size for chondrocyte culture were named Hμ-SL2, Hμ-SL4, SHμ-SL2 and SHμ-SL4. The perforation, porosity, mechanical strength, biocompatibility, and proliferation characteristics of the hydrogel scaffold and its influence on chondrocyte differentiation are discussed. Results show that the addition of porogen increases the porosity of the hydrogel scaffold. Conversely, when porogens with the same particle size are added, the pore size decreases as the amount of porogen increases. The perforation effect of the hydrogel scaffolds formed by the porogen is better at 88–177 μm compared with that at 44–74 μm. Cytotoxicity analysis showed that all the prepared hydrogel scaffolds were non-cytotoxic, indicating that no cross-linking agent residues that could cause cytotoxicity were found. In the proliferation and differentiation of the chondrocytes, the SHμ-SL4 hydrogel scaffold with the highest porosity and strength did not achieve the best performance. However, due to the compromise between perforation pores, pore sizes, and strength, as well as considering cell proliferation and differentiation, Hμ–SL4 scaffold provided a more suitable environment for the chondrocytes than other groups; therefore, it can provide the best chondrocyte growth environment for this study. The development of hydrogels with customized pore properties for defective cartilage is expected to meet the requirements of the ultimate clinical application.

Devices and medicines used in the medical field must be sterile. Gamma (γ)-irradiation is commonly used for sterilization because its high rate of penetration ensures uniform sterilization. To confirm that hydrogel macrosphere carriers inherit excellent liquid absorption with no cytotoxicity after γ-irradiation sterilization, investigating whether the physiochemical properties of hydrogel macrospheres differ before and after sterilization is essential. The present study evaluated the influence of the recommended 25-kGy γ-irradiation dose on the physicochemical characteristics and in vitro release of bovine serum albumin and vancomycin (an antibiotic medication) from alginate/gelatin with a w/w ratio of 1/4 crosslinking gel macrospheres. Gel macrosphere properties before and after sterilization were compared according to optical and scanning electron microscopy, infrared spectroscopy analysis, the amino residual crosslinking index, water absorption, degradation, sterility assurance, in vitro drug release, antibacterial ability, and cytotoxicity. The crosslinking index was almost unchanged; however, the γ-irradiation caused in situ hydrogel debonding and recrosslinking, which led to a decrease in the water absorption and increase in the degradation rate of the macrospheres after immersion. The release of gel macrospheres carrying vancomycin did not significantly affect antibacterial ability or biocompatibility after γ-irradiation. Accordingly, we conclude that γ-irradiation is suitable for macrospherical formulation.

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.