Bisphosphonate-Modified Functional Supramolecular Hydrogel Promotes Periodontal Bone Regeneration by Osteoclast Inhibition

Abstract

Regeneration of periodontal tissue remains a challenge. Under periodontitis, osteoclasts are overactivated and bone loss occurs. We incorporated sodium alendronate (Alen), a medication commonly used to treat osteoporosis, into a supramolecular hydrogel system in order to create a novel biomaterial that would promote periodontal bone regeneration by inhibiting osteoclast overactivation. The Nap-Gly-Phe-Phe (NapGFF) peptide chain was modified to synthesize the functional Nap-Alen gelator. Afterward, the Nap-Alen/HAP supramolecular hydrogel composite with a suitable hydroxyapatite (HAP) ratio was constructed, which has outstanding mechanical properties and 3D structure. In addition to its good biocompatibility, it can inhibit the proliferation of bone marrow-derived macrophages (BMDMs) and differentiation of osteoclasts. Due to the simultaneous introduction of porous HAP, the hydrogel with a nanofiber structure was formed into a 3D mesh-like sparse porous composite hydrogel. While enhancing the mechanical properties of the gel, the porous structure facilitated the attachment and migration of bone regeneration-related cells. Therefore, it can effectively promote the regeneration of periodontal bone. In the future, by modifying the biophysical properties and loading stem cells or cytokines, this supramolecular hydrogel composite constructed in this study may provide a new strategy for tissue regeneration engineering and provide a preliminary experimental basis for relevant clinical translational studies.

Multifunctionalized and Dual‐Crosslinked Hydrogel Promotes Inflammation Resolution and Bone Regeneration via NLRP3 Inhibition in Periodontitis

“…We created rat experimental periodontitis models by combining silk ligature with P. gingivalis injection, as previously described, in accordance with the mechanism of periodontal inflammation, which holds that periodontal pathogens were the initiator of host inflammatory response and tissue resorption (Figure 7B). [44,51,52] Confirming by micro-CT and H&E staining, the periodontitis models were verified to be successfully established (Figure S13 and S14, Supporting Information). Following the induction of periodontitis, there was a substantial increase in the cementoenamel junctionalveolar bone crest (CEJ-ABC) distance to 0.92 AE 0.88 mm compared to the control group (p < 0.001) (Figure S15, Supporting Information).…”

“…Then, we established the rat periodontitis models according to our previous study. [ 52 ] Briefly, SD rats were fully anesthetized with 10% chloral hydrate (0.35 mL per 100 g), 15 # –40 # nickel–titanium root canal files, and silk and stainless‐steel ligature wires were used to induce periodontitis. Subsequently, P. gingivalis (20 μL, 1.0 × 10 8 CFU mL −1 ) was injected subgingivally every 2 d around bilateral second molars for 4 times.…”

Recent advances in composite hydrogels: synthesis, classification, and application in the treatment of bone defects

“…Tan et al prepared Nap-Alen/HAp porous hydrogel composites by doping sodium alendronate (Alen) and a Nap-Gly-Phe-Phe (NapGFF) peptide chain into a supramolecular hydrogel system. 155 The introduction of Alen could effectively inhibit the activation of bone marrow-derived macrophages and the differentiation of osteoclasts. On the other hand the introduction of HAP promoted the differentiation of osteoblasts.…”

Supramolecular immunotherapy on diversiform immune cells

“…Supramolecular materials are highly ordered functional selfassembled materials driven by dynamically reversible noncovalent forces, electrostatic contacts, hydrophobic effects, hydrogen bonding, metal-ligand coordination, p-p stacking and host-guest interactions that hold together monomers or components of macromolecules. 146,147 Supramolecular materials have been widely used in the field of medicine, such as in heart valves or catheters,148 delivery of antineoplastic drugs, 149 to promote bone regeneration, 150 and for disease treatment, etc. 151 We have divided them into three categories according to the different molecules delivered, the different supramolecular materials and the different functions.…”

“…Supramolecular materials have been widely used in the field of medicine, such as in heart valves or catheters,148 delivery of antineoplastic drugs, 149 to promote bone regeneration, 150 and for disease treatment, etc. 151 We have divided them into three categories according to the different molecules delivered, the different supramolecular materials and the different functions.…”