SBIR-STTR Award

Osteoarthritis (OA) is the leading cause of chronic disability in the United States. A clinical goal in the treatment and prevention of OA is to develop replacement cartilage using tissue engineering (TE) technologies. Although TE cartilage presently lacks the mechanical stability of native cartilage, studies have demonstrated that mechanical stability can be enhanced with specific chemical and mechanical stimuli. To speed the discovery of optimal stimulation protocols, research platforms need to be available that enable fast, clear and reliable communication of functional outcomes (i.e material properties). Towards this goal, we introduce a six-chamber bioreactor that combines the efficiency of batch testing with the accuracy normally reserved for dedicated single-specimen material test systems. This system is therefore capable of mapping functional development of six individual specimens exposed to highly-specific mechanical stimulation protocols. To remain cost-effective and portable, the bioreactor leverages system redundancies to eliminate hardware. The specific aim of this study is to test the bioreactor's capacity to deliver accurate mechanical stimulations and material property evaluations in all six test chambers. The effect of loading conditions and specimen geometry on accurate mechanical stimulation will be quantified using external sensors. The viscoelastic material properties of soft TE scaffolds and stiff cartilage plugs will be characterized in both the six-chamber bioreactor and a conventional single-stage testing device. Results between the bioreactor and the model testing system will be statistically compared. If validation of the bioreactor is successful, we envision this product will provide an economical and reliable research platform that fosters TE technology transfer.

Public Health Relevance:
Tissue engineering of articular cartilage presents a promising strategy for treatment of osteoarthritis, a debilitating and prevalent disease. Cartilage engineering techniques, however, are currently unable to reproduce the mechanical properties critical to native cartilage, thus impeding the transfer of TE technology to patient care. A bioreactor is therefore proposed to facilitate the rapid discovery of mechanical conditions that promote the synthesis of mechanically viable tissue.

Thesaurus Terms:
Achievement; Achievement Attainment; Amplifiers; Arthritis, Degenerative; Biochemistry; Biomechanics; Bioreactors; Body Tissues; Bone; Bone And Bones; Bones And Bone Tissue; Cartilage; Cartilage, Articular; Cartilagenous Tissue; Chemicals; Chemistry, Biological; Chronic; Clinical; Communication; Connective Tissue; Degenerative Polyarthritis; Development; Devices; Disease; Disorder; Electromagnetic; Electromagnetics; Engineering; Engineerings; Europe; Evaluation; Fibrocartilages; Fostering; Generalized Growth; Goals; Graphical Interface; Growth; Individual; Laboratories; Maps; Marketing; Materials Testing; Measurement; Measures; Mechanical Stimulation; Mechanics; Method Loinc Axis 6; Methodology; Methods; Methods And Techniques; Methods, Other; Modeling; Morphology; Operation; Operative Procedures; Operative Surgical Procedures; Osteoarthritis; Osteoarthrosis; Partner In Relationship; Patient Care; Patient Care Delivery; Performance; Phase; Prevention; Property; Property, Loinc Axis 2; Protocol; Protocols Documentation; Research; Research Specimen; Sttr; Small Business Technology Transfer Research; Software Validation; Software Verification; Specimen; Speed; Speed (Motion); Staging; Stimulus; Structure Of Articular Cartilage; Surgical; Surgical Interventions; Surgical Procedure; System; System, Loinc Axis 4; Techniques; Technology; Technology Transfer; Testing; Tissue Engineering; Tissue Growth; Tissues; Translations; United States; Validation; Articular Cartilage; Bone; Cost; Degenerative Joint Disease; Design; Design And Construction; Designing; Disability; Disease/Disorder; Engineered Tissue; Experiment; Experimental Research; Experimental Study; Functional Outcomes; Graphic User Interface; Graphical User Interface; Hypertrophic Arthritis; Improved; In Vivo; Innovate; Innovation; Innovative; Mate; Meetings; Ontogeny; Public Health Relevance; Regenerative; Research Study; Scaffold; Scaffolding; Scale Up; Sensor; Soft Tissue; Surgery; Treatment Strategy

Osteoarthritis (OA) is the leading cause of chronic disability in the United States. A clinical goal in the treatment and prevention of OA is to develo replacement cartilage using tissue engineering (TE) technologies. Although TE cartilage currently lacks the mechanical resilience of native cartilage, the mechanical properties of TE constructs can be enhanced by applying chemical and mechanical stimuli during culture. To speed the discovery of optimal stimulation protocols, research platforms need to be available that enable fast, clear and reliable communication of functional outcomes (i.e. mechanical properties). Towards this goal, we introduce a compact six-station bioreactor that combines the efficiency of batch testing with the accuracy normally reserved for dedicated single-specimen material test systems. In the highly successful phase I feasibility study, an innovative method was proven to deliver accurate dynamic stimulations and evaluate mechanical properties in six stations. This technology can now be incorporated into a multi-axial frame that uses hybrid and adaptive controls to maximize testing efficiency and flexibility. The first three aims of this application are to 1) increase throughput, 2) add loading modalities and 3) automate performance and analysis tools. The effect of these modifications on mechanical accuracy will be verified using external sensors and imaging methods. Hydrogels and bovine cartilage will be tested in the high- throughput bioreactor and a conventional single-station test system to validate the bioreactors automated measurement of mechanical properties. System robustness will be determined by quantifying the effect of operating the bioreactor for millions of cycles. In the fourth aim, bioreactor prototypes will be distributed to three cartilage TE laboratories to evaluate and optimize the bioreactor prior to commercial launch. Successful completion of the study aims will provide an efficient, reliable and flexible research platform to advance the development and clinical transfer of cartilage TE technology.

Public Health Relevance:
Tissue engineering of articular cartilage presents a promising strategy for treatment of osteoarthritis, a debilitating and prevalent disease. Cartilage engineering techniques, however, are currently unable to reproduce the mechanical properties critical to native cartilage, thus impeding the transfer of TE technology to patient care. A bioreactor is therefore proposed to facilitate the rapid discovery of mechanical conditions that promote the biosynthesis of mechanically viable tissue.