Influence of DMP1 on the nanomechanical properties of newly formed bone tissue in the peri-implant region and critical calvarial defects under osteoporotic conditions and characterization of Gelfoam® scaffold functionalized with the biomolecule

• Grant number: 25/17366-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: March 01, 2026
• End date: February 27, 2027
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Roberta Okamoto
• Grantee: Laura Vidoto Paludetto
• Supervisor: Anne George
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Institution abroad: University of Illinois at Chicago (UIC), United States
• Associated to the scholarship: 24/19648-5 - Local release of DMP1 and its impact on bone repair in osteoporotic rats, BP.DR

Abstract

Osteoporosis is a systemic metabolic disease that reduces bone mineral density andcompromises bone structural quality, potentially impairing implant osseointegration and therepair of critical bone defects. Dentin Matrix Protein 1 (DMP1) is a non-collagenousphosphoprotein of the extracellular matrix, highly expressed by osteoblasts and matureosteocytes, playing a key role in hydroxyapatite crystal nucleation, collagen matrix organization,and regulation of bone mineralization. Animal models with DMP1 deletion exhibit severemineralization defects and mechanically fragile bone, whereas its overexpression is associatedwith increased bone formation and enhanced biomechanical properties. Despite its potential,DMP1 has never been tested in in vivo osteoporosis models, making it a promising target forregenerative strategies in compromised bone microenvironments. The doctoral project conductedin Brazil investigates the impact of implants and scaffolds functionalized with DMP1 on peri-implant bone repair and critical calvarial defects in osteoporotic rats through histological,microtomographic, and molecular analyses; however, it does not include a direct evaluation ofthe mechanical properties of regenerated bone, a crucial parameter for determining the clinicalfunctionality of the induced regeneration. This BEPE proposal aims to address this gap from twocomplementary perspectives. In Phase I, the nanoindentation technique will be applied toquantify hardness (H) and reduced elastic modulus (Er) at the micrometric scale, allowing acomparison of the biomechanical quality of newly formed bone around conventional implants(TI) and DMP1-functionalized implants (TID), as well as in critical calvarial defects filled withblood clot (CC), Gelfoam® (CG), or Gelfoam® functionalized with DMP1 (CGD), therebyverifying whether DMP1 promotes the formation of structurally competent tissue capable ofsupporting functional loads. In Phase II, the Gelfoam® scaffold, with or without DMP1functionalization, will be characterized for protein incorporation and release (UV-Visspectroscopy), cytocompatibility (MTT assay), and osteogenic potential(alkaline phosphatase activity and mineralized nodule formation), correlating scaffoldphysicochemical properties with cellular responses and providing mechanistic evidence toexplain the in vivo results. All data will undergo appropriate statistical analysis, with comparisonsbetween groups performed using parametric or non-parametric tests depending on data normality,and the significance level set at p < 0.05. This integrated approach provides a thorough evaluationof DMP1, allowing a detailed characterization of its effects on structurally competent boneregeneration in osteoporotic models, thereby strengthening the scientific basis for futuretherapeutic strategies in compromised tissues.