The long-term goal of this research is to develop a semi-rigid bioactive scaffold based on cellulose- nanodiamond (CeND) porous fibers for craniofacial bone tissue regeneration. The bioactive scaffolds will be prepared in the form of fibers using the electrospining technique. The CeND are modified with growth and adhesion factors aiming to improve the rate of bone tissue regeneration. We will achieve the overall goal of this research by pursuing three main specific aims: 1) To formulate bioactive CeND solutions to generate porous scaffolds; 2) To evaluate the biocompatibility of the bioactive CeND scaffolds in vitro using a bioreactor to generate 3D tissue models; 3) To determine the osteoinductive capacity of bioactive CeND scaffolds in cranial defects in rats. We hypothesize that by incorporating osteoinductive growth factors (i.e. BMP-2) along with adhesion factors (i.e. KSRS and RGD peptides) in CeND-fibered scaffolds, we will be able to enhance the deposition rate of newly formed mineralized tissue along the scaffold. Once the bioactive scaffolds are fabricated we will physically, mechanically and biologically characterize the fibers with and without the growth and adhesion factors. The biological characterization will be performed in-vitro utilizing human mesenchymal stem cells (MSCs). Specifically, we will use inmmunohistochemical techniques to determine the ability of the cells to growth, mature, adhere and differentiate when in contact with the bioactive flexible scaffolds. The in- vitro experiments will be performed in Slow-Turning Lateral Vessel (STLV) bioreactor in order to generate 3D tissue models over the scaffolds. We expect that this in-vitro technique will allow us to better predict the performance of the scaffolds in-vivo. We will be able to answer fundamental questions regarding cell-surface interactions with the goal of proposing a flexible bioactive scaffold with enhanced biomimetic properties. This work will shed light on the use of semi-rigid scaffolds for craniofacial bone tissue regeneration and repair that is of utmost importance to tackle medical conditions such as the cleft palate and other craniomaxillofacial conditions.

Public Health Relevance

More than 6% of a total of 1,600,000 bone grafts implanted annually around the world are craniofacial bone grafts. With the growing population in the US, more cranial grafts will be required and the cost of cranial reconstruction will be higher. In this work, we explore the fabrication of bioactive cellulose-nanodiamond porous scaffolds for craniofacial bone tissue regeneration applications.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Enhancement Award (SC1)
Project #
5SC1GM127220-02
Application #
10001567
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Krasnova, Irina N
Project Start
2019-09-01
Project End
2023-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Puerto Rico Rio Piedras
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
143960193
City
San Juan
State
PR
Country
United States
Zip Code
00931