Holloway Research Group

Designing biomimetic materials and tissue engineering strategies for orthopedic applications.

Orthopedic injuries and diseases, including meniscal tears and degenerative disc disease, are a significant health concern in the United States. Current treatments typically rely on donor tissues or removal of the damaged tissue.

Regardless of the treatment option, most injured tissues never regain complete functionality, which can cause mild to severe degeneration of the surrounding tissues. Using an innovative approach, our research group develops new tissue engineering strategies aimed at replicated and/or restoring the biological and mechanical cues required for tissue function and to prevent further tissue degeneration.

The objective of our research program is to restore musculoskeletal tissue function through the use of biomimetic materials, with a focus on discovering how biophysical and biochemical cues affect ultimate tissue structure and functionality.

Current Research Areas

Research Area 1: Controlled biomolecule delivery

The clinical gold standard to promote bone repair for severe nonunion fractures, spinal fusions, joint revisions, and to fill voids after tumor resection remains autograft bone. Limitations of this treatment include: a limited tissue supply, donor site morbidity, and poor integration. The use of bone morphogenetic proteins (BMPs), extracellular molecules capable of promoting osteoblast differentiation, are FDA-approved and show promise as therapeutics for supporting bone regeneration. Currently approved therapies, however, are costly and require supraphysiological doses for the desired osteoinductive effect, which can result in significant adverse side effects. One strategy to improve BMP efficacy is to co-deliver BMP with other biomolecules that may synergistically improve BMP-induced osteogenesis. Several signal transduction pathways are known to regulate osteoblast function; nonetheless, the exact role and timing of each pathway during bone repair remains unclear. In this research area, we aim to develop a better understanding of the relationship between biomolecule presentation and osteogenic gene expression using synthetically engineered materials capable of controllably and independently delivering multiple biomolecules.

Research Area 2: Engineering interfacial tissue

A majority of musculoskeletal tissue engineering research has focused on the regeneration of one particular tissue type (i.e. bone, cartilage, ligament) and neglected to address the musculoskeletal tissue interfaces that serve as the connection between these tissues. Musculoskeletal tissue interfaces, such as the cartilage-bone and ligament-bone interface, gradually transition from one orthopedic tissue to another and often possess distinct physical and biological properties compared to the connecting tissues. Furthermore, musculoskeletal tissue interfaces play an important biomechanical role efficiently transferring load between orthopedic tissues. Typical surgical repair methods to treat musculoskeletal tissue injuries fail to adequately regenerate the necessary interfacial tissue, resulting in inferior biomechanical function and ultimately compromising long-term clinical outcome. In this research area, we develop structurally graded scaffolds in order to better understand cellular behavior in the presence of biophysical and biochemical gradients in order to lend insight into biomaterial design for improved interfacial tissue regeneration.

Research Area 3: Dynamic cell-material interactions

Despite significant research and funding, tissue-engineered constructs have been largely unable to regenerate tissue with the same biomechanical functionality as native tissue. A major translational challenge is a lack of adequate characterization techniques that effectively bridge the gap between traditional in vitro techniques and in vivo models. Furthermore, there is a significant need for techniques that allow for the systematic evaluation of cell-material interactions in a three-dimensional, physiologically relevant environment. In this research area, we develop novel bioreactors capable of biomechanically relevant loading in order to better understand cell-material interactions and how specific biophysical and biochemical biomaterial cues impact tissue repair and functionality.