2015 IR&D Annual Report

Development of a Novel Drug-Loaded Composite Scaffold as Bone Graft Substitute Using Advanced Materials Technology, 01-R8415

Principal Investigators
Jian Ling
Joo Ong (UTSA)

Inclusive Dates: 09/01/13 – 12/31/14

Background — More than three million musculoskeletal procedures are performed annually in the United States to address damage to bone tissue due to trauma (from automobile accidents and military operations), to fix congenital deformities or bone diseases, and to heal defects created upon the removal of cancerous lesions. Currently, the use of autologous grafts is considered the "gold standard" for grafting procedures. However, this approach is associated with tissue scarcity and donor site morbidity due to the additional surgery. The objective of this project was to develop a novel biomimetic bone substitute loaded with growth factor for musculoskeletal procedures to address the growing unmet needs of the $2.5 billion per year bone graft market.

Approach — SwRI used a patented technology to fabricate biomimetic collagen-hydroxyapatite (Col-HA) scaffolds with different HA loadings through a perfusion-based method. Then the Col-HA scaffolds with different degrees of HA loadings and stiffness were evaluated by human mesenchymal stem cells (hMSCs) cultured on these scaffolds in osteogenic media. Based on the osteogenic response of hMSCs, an optimized mineralization level was identified. At UTSA, microparticles encapsulation with growth factor TGF-β were developed, which would be incorporated into the biomimetic scaffolds to form a drug-loaded composite grafting material for bone repair.

Figure 1: caption
Figure 1: (A) MicroCT shows the mineral volume of the composite scaffolds with different mineralization time. (B) The comparison of osteogenic gene expression after the hMSCs were cultured on the scaffolds with different mineralization levels (0%, 58%, and 72%).

Accomplishments — Highly porous collagen scaffolds were fabricated. The scaffolds were exposed to mineralization solutions using a perfusion flow bioreactor system to form Col-HA composite scaffolds. Col-HA composites of different mineral loadings were fabricated by varying the mineralization time (Figure 1A). The osteogenic gene expression illustrated in Figure 1B suggests that scaffolds with a medium mineralization level around 58 percent had the highest osteogenic response from hMSCs.

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Southwest Research Institute® (SwRI®), headquartered in San Antonio, Texas, is a multidisciplinary, independent, nonprofit, applied engineering and physical sciences research and development organization with 9 technical divisions.