Exploiting Bisphosphonate–Bioactive‐Glass Interactions for the Development of Self‐Healing and Bioactive Composite Hydrogels

Abstract

Hydrogels are widely recognized as promising candidates for various biomedical applications, such as tissue engineering. Recently, extensive research efforts have been devoted to the improvement of the biological and mechanical performance of hydrogel systems by incorporation of functional groups and/or inorganic particles in their composition. Bisphosphonates are a class of drugs, commonly used for treatment of osteoporosis, which exhibit a strong binding affinity for hydroxyapatite. In this study, the binding affinity of a bisphosphonate-functionalized polymer, hyaluronan, toward a bioactive glass (i.e., 45S5 Bioglass) is evaluated using force-distance measurements with atomic force microscopy. The strong interaction between bisphosphonate and bioactive glass is then exploited to develop organic-inorganic composite hydrogels and the viscoelastic and self-healing ability of these materials are investigated. Finally, the stability and mineralization behavior of these hydrogels are evaluated in simulated body fluid. Following this approach, injectable, bioactive and self-healing organic-inorganic composite hydrogels are produced, which mineralize abundantly and rapidly in simulated body fluid. These properties render these composite gels suitable for applications in bone-tissue engineering.

Composite Colloidal Gels Made of Bisphosphonate‐Functionalized Gelatin and Bioactive Glass Particles for Regeneration of Osteoporotic Bone Defects

“…45S5 BG (Bioglass) particles were used as the inorganic building blocks since this glass type is the most common type of BG due to its strong bioactivity and biodegradability . We functionalized the gelatin particles with calcium‐binding bisphosphonate groups not only for their capacity to bind to calcium‐containing BGs, but also due to their antiosteoporotic efficacy . We first used a colloidal probe atomic force microscopy (AFM) technique to quantify the effect of the bisphosphonate functionalization of gelatin particles on the interparticle adhesion forces between gelatin and BG particles.…”

Self‐Healing Biomaterials: From Molecular Concepts to Clinical Applications

“…Important parameters which determine the properties of these hydrogels are the binding affinity between particles and polymer chains, the size of particles, the persistence length of polymers, the polymer concentration, and the crosslinking density of the gel network, i.e., the number of particles per gel volume. So far, hydrophobic, electrostatic, coordination interactions as well as molecular recognition motifs have been exploited to prepare this class of self‐healing biomaterials.…”

“…Recent studies have shown that bisphosphonate functionalization of hyaluronic acid renders this polymer highly adhesive to calcium phosphate,[101b] calcium silicates,[101a] and magnesium silicate[101c] particles. Consequently, by exploiting these strong yet reversible coordination bonds between polymers and particles, injectable and self‐healing composite hydrogels have been synthesized which display promising results with respect to bone regeneration[101a,b] and drug delivery[101c] applications. In general, bisphosphonates exhibit a strong binding affinity for the mineral inorganic phase of bone, i.e., hydroxyapatite .…”

“…In a recent study, we found that bisphosphonate‐functionalized hyaluronic acid exhibits significantly stronger binding affinity for a commonly used calcium silicate phase (45S5 bioactive glass) than for hydroxyapatite, leading to the formation of more elastic and self‐healing composite hydrogels. In addition, the formation of hydrogels by combination of this polymer with magnesium silicate nanoparticles[101c] suggests that this strategy can be extended to a wide range of divalent cation‐containing inorganic phases including glasses doped with therapeutic ions to produce self‐healing biomedical hydrogels. Moreover, other types of coordination‐type interactions can be used to develop these self‐healing hydrogel systems.…”

“…For instance, Holten‐Andersen et al recently developed a self‐healing hydrogel by exploiting coordination bonds between a catechol‐terminated PEG and iron oxide nanoparticles. In an effort to improve the mechanical properties and in vivo cohesion of this class of hydrogels for bone regeneration, Shi et al[101d] recently developed a dual crosslinked hydrogel by functionalizing hyaluronic acid with both bisphosphonate and acrylamide groups. Injectable and self‐healing hydrogels could be formed by mixing the functionalized polymer with calcium phosphate‐coated silk microfibers.…”