Advancements in Hydrogel-Based Drug Sustained Release Systems for Bone Tissue Engineering

Abstract

Bone defects caused by injury, disease, or congenital deformity remain a major health concern, and efficiently regenerating bone is a prominent clinical demand worldwide. However, bone regeneration is an intricate process that requires concerted participation of both cells and bioactive factors. Mimicking physiological bone healing procedures, the sustained release of bioactive molecules plays a vital role in creating an optimal osteogenic microenvironment and achieving promising bone repair outcomes. The utilization of biomaterial scaffolds can positively affect the osteogenesis process by integrating cells with bioactive factors in a proper way. A high water content, tunable physio-mechanical properties, and diverse synthetic strategies make hydrogels ideal cell carriers and controlled drug release reservoirs. Herein, we reviewed the current advancements in hydrogel-based drug sustained release systems that have delivered osteogenesisinducing peptides, nucleic acids, and other bioactive molecules in bone tissue engineering (BTE).

Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue

“…Hydrogels and scaffolds possess desirable qualities to either assist in the regeneration of bone or to provide a bone substitute [ 58 , 65 , 70 ]. Hydrogels are versatile in geometry and can be used as an injectable or for transplantation.…”

“…Both allow for cellular induction, dynamic multi-cellular interactions, which can then lead to cellular differentiation in situ. However it has become apparent in recent years that fabrication, biocompatibility, bio-degradability and bio-integration, immunogenicity, cytotoxicity, gelation time, porosity, incorporation of metal ions, payload release profile, cellular infiltration, delivery of a vascular permissive environment, bone adhesiveness, degradation time, mechanical and anti-bacterial properties need to be considered when developing hydrogels, scaffolds or composites [ 70 , 71 , 72 , 73 , 74 , 75 , 76 ]. The natural and synthetic materials are fabricated into a range of structures including but not limited to injectable hydrogels, microbeads, nanogels, hydrogel fibers, biofilms, membranes, solid porous scaffolds or sponges.…”

“…Using a similar concept, ZnO/nanocarbon modified fibrous scaffolds have demonstrated osteogenic and antibacterial properties, albeit in vitro [ 87 ]. While there are still limitations with regard to the functional capacity of hydrogels and scaffolds, the unique and versatile configurations and continuous refinement in combination with BMSC treatment holds considerable promise for bone regeneration [ 70 , 74 ].…”

MicroRNA-activated hydrogel scaffold generated by 3D printing accelerates bone regeneration

“…Natural hydrogels usually have weak mechanical properties which are not sufficient to meet the requirements of tissue repair. The modification in a restricted scope by chemical/physical crosslinking methods or composite strategies is simple and effective [ 29 , 30 ]. In this study, alginate was physically crosslinked with Ca 2+ ions and gelatin was chemically crosslinked with different concentrations of GTA, which might alter the mechanical properties of MAHS.…”

On the road to smart biomaterials for bone research: definitions, concepts, advances, and outlook

“…101,102 Due to the constant evolution and significant amount of information available regarding drug delivery systems for hard tissue regeneration, readers are referred to recent excellent reviews addressing this subject matter. [103][104][105] Summary Different biomaterial properties and characteristics such as porosity, roughness, chemistry, surface charge, and mechanical properties drive specific interactions with bone cells. A variety of in vitro and in vivo model systems have been used to study materials with characteristics that can mimic a more realistic and suitable environment for promoting cell functions and improve bone modeling and remodeling.…”