# Mechanisms Mediating Osseointegration of 3D Printed Titanium Constructs

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $533,466

## Abstract

This proposal addresses the growing clinical need in dentistry and orthopaedics for materials that enable rapid
osseointegration and earlier loading times for implants in bone that has been compromised by trauma or
disease. 38 million US adults will have no natural teeth by 2020. Implant-supported dentures significantly
improve quality of life in comparison to removable dentures, but many denture patients experience
considerable bone loss, risking exposing the mandibular nerve during surgery and limiting implant placement.
The aging population has an increased need for technologies that provide predictable implant osseointegration
in orthopaedic sites (e.g. spine). Medical treatment for metabolic bone diseases like osteoporosis improve
implant success, but many patients are not treated with these drugs. Osteoinductive agents like BMPs can
improve clinical outcomes, but these technologies are expensive, can have negative side effects, and for some
applications are contra-indicated. Our goal is to exploit the physical surface properties of dental and
orthopaedic implants to generate new bone in patients lacking sufficient supporting bone without relying on
pharmacologic interventions. Our work has shown that the microscale and nanoscale properties of 2D titanium
(Ti) and Ti-alloy surfaces are sufficient to drive osteoblast differentiation of multipotent mesenchymal stem cells
(MSCs) in vitro and increase the rate of new bone formation in vivo in animals and patients, improving
osseointegration and implant stability. Additive manufacturing (AM) makes it possible to design-patient specific
implants, but the complex geometries that are needed make modifications to interior surfaces of 3D constructs
difficult to achieve. To overcome this technology limitation, we will develop our novel magnesio(calcio)thermic
[M(C)T] process for generating osteogenic nanostructure on both exterior and interior surfaces of 3D AM-
derived Ti-6Al-4V implants. We will: (1) Determine the mechanism(s) of the M(C)T process controlling the
surface nanostructure and use this understanding to tailor nanoscale surface features for enhanced osteoblast
differentiation on AM-derived 3D implants; (2) Determine the mechanisms that mediate the differential effects
of surface design features on planar cell polarity and MSC commitment to an osteoblast lineage fate (i.e.,
obligatory change in shape from flattened MSCs, which can migrate, adhere to the implant, and proliferate, to
columnar secretory osteoblasts, which synthesize and mineralize bone matrix); and (3) Assess how changes in
surface design impact bone formation and remodeling in vitro by understanding how MSCs modulate
osteoclast activity and in vivo using aged male and female rats to assess any sex differences, estrogen-
deficient rats as a model of compromised bone health, and rabbit femurs as a model of function under load-
bearing conditions. Our studies take advantage of the investigative team's skills in cell and molecula...

## Key facts

- **NIH application ID:** 9846203
- **Project number:** 5R01AR072500-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Barbara D. Boyan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $533,466
- **Award type:** 5
- **Project period:** 2019-01-07 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9846203

## Citation

> US National Institutes of Health, RePORTER application 9846203, Mechanisms Mediating Osseointegration of 3D Printed Titanium Constructs (5R01AR072500-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9846203. Licensed CC0.

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