Synthasome (United States)

On May 22, 2017, the National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) hosted a roundtable on "Innovative Treatments for Enthesis Repair." A summary of the roundtable discussion, as well as a list of the extramural participants, can be found at https://www.niams.nih.gov/about/meetings-events/roundtables/roundtable-innovative-treatments-enthesis-repair. This paper reviews the challenges and opportunities for developing effective treatment strategies for enthesis repair that were identified at the roundtable discussion.

Enhanced tendon and ligament repair would have a major impact on orthopedic surgery outcomes, resulting in reduced repair failures and repeat surgeries, more rapid return to function, and reduced health care costs. Scaffolds have been used for mechanical and biologic reinforcement of repair and regeneration with mixed results. This review summarizes efforts made using biologic and synthetic scaffolds using rotator cuff and ACL as examples of clinical applications, discusses recent advances that have shown promising clinical outcomes, and provides insight into future therapy.

The hydraulic resistance R across osteochondral tissue, especially articular cartilage, decreases with degeneration and erosion. Clinically useful measures to quantify and diagnose the extent of cartilage degeneration and efficacy of repair strategies, especially with regard to pressure maintenance, are still developing. The hypothesis of this study was that hydraulic resistance provides a quantitative measure of osteochondral tissue that could be used to evaluate the state of cartilage damage and repair. The aims were to (1) develop a device to measure R in an arthroscopic setting, (2) determine whether the device could detect differences in R for cartilage, an osteochondral defect, and cartilage treated using a hydrogel ex vivo, and (3) determine how quickly such differences could be discerned. The apparent hydraulic resistance of defect samples was ~35% less than intact cartilage controls, while the resistance of hydrogel-filled groups was not statistically different than controls, suggesting some restoration of fluid pressurization in the defect region by the hydrogel. Differences in hydraulic resistance between control and defect groups were apparent after 4 s. The results indicate that the measurement of R is feasible for rapid and quantitative functional assessment of the extent of osteochondral defects and repair. The arthroscopic compatibility of the device demonstrates the potential for this measurement to be made in a clinical setting.

Numerous scaffolds have been proposed for use in connective tissue engineering. Although these scaffolds direct cell migration and attachment, many are biologically inert and thus lack the physiological stimulus to attract cells and induce mitogenesis and matrix synthesis. In the current study, a bioactive scaffold was created by combining a synthetic scaffold with growth factor-rich plasma (GFRP), an autologous concentration of growth factors derived from a platelet-rich plasma preparation. In vitro tendon cell proliferation and matrix synthesis on autologous GFRP-enriched scaffolds, autologous serum-enriched scaffolds, and scaffolds alone were compared. The GFRP preparation was found to have a 4.7-fold greater concentration of a sentinel growth factor (transforming growth factor-beta1) compared with serum. When combined with media containing calcium, the GFRP produced a thin fibrin matrix over and within the GFRP-enriched scaffolds. Cell proliferation assays demonstrated that GFRP-enriched scaffolds significantly enhanced cell proliferation over autologous serum and control groups at both 48 and 72 h. Analysis of the scaffolds at 14, 21, and 28 days revealed that GFRP-enriched scaffolds significantly increased the deposition of a collagen-rich extracellular matrix when compared with the other groups. These results indicate that GFRP can be used to enhance in vitro cellular population and matrix deposition of tissue-engineered scaffolds.