Novel Granular Hydrogels for Theranostic Management of Periodontitis

About This Grant

Project Summary Periodontitis (PD) is an oral inƲammatory disease caused by the dysbiosis of the oral microbiota. The existing diagnostic and treatment methods do not offer satisfactory outcomes and do not present the active status of the disease. The ideal platform for the management of PD is to target the multiple factors (bacteria, biofllm, inƲammatory molecules), simultaneously executing real-time analysis of the disease. This simultaneous diagnosis and therapy can be performed by a theranostic (therapy + diagnosis) biomaterial, and our long-term goal is to develop and validate multifunctional theranostic platforms for oral inƲammatory diseases. The present study focuses on the synthesis and validation of granular hydrogel platforms for the theranostic management of periodontitis. Granular hydrogels (set of tightly packed microgels) are advantageous when compared to conventional bulk hydrogels as they can act as heterogenous carriers for the encapsulation/surface functionalization of an array of agents. In the present work we are proposing the synthesis of granular hydrogels made up of thiolated chitosan (ThCS) microgels encapsulating therapeutic agents or surface functionalized with diagnostic molecules. In summary, the proposed speciflc aims are to synthesis, characterize and validate (1) Diagnostic granular hydrogel, comprised of ThCS microgels functionalized with MMP -2 and -9 susceptible MMPSense™ 750 Ʋuoropeptide for the precise diagnosis of PD; (2) Therapeutic granular hydrogel, comprised of ThCS microgels encapsulated with therapeutic agents thymol and Zinc substituted hydroxyapatite for the multimodal therapy of PD and (3)Theranostic granular hydrogels comprised on ThCS microgels either encapsulating the therapeutic agents or functionalized with diagnostic peptide capable of performing precise diagnosis and multimodal therapy of PD. The prepared granular hydrogels will be characterized (morphology, rheology, in vitro degradation, drug release, sensitivity & speciflcity of the Ʋuoropeptide) before diagnostic / therapeutic validation. The central hypothesis is that the theranostic granular hydrogel can perform precise diagnosis of PD as MMP- 2 & -9 are expressed actively in the periodontal pocket which will cleave the MMPSense™ 750 Ʋuoropeptide resulting in infra-red Ʋuorescence, while performing multimodal therapy mediated by thymol (antibacterial & anti-inƲammatory) and zinc substituted hydroxyapatite (antimicrobial and anti-biofllm). The skill set to accomplish this proposed project will be acquired during the K99 phase with the support of my mentoring team (Drs. Ana Fugolin, Jack Ferracane, Phillip Marucha and Luiz Bertassoni). The combination of new techniques and career development trainings acquired during the K99 mentored phase, my prior expertise in biomaterials synthesis and characterization will lay foundation of my independent career focused on theranostic biomaterials. Additionally, this proposal will be a proof-of-concept for understanding how theranostic biomaterials can be utilized in dentistry which was previously conflned to the fleld of oncology.