Assessment of a Synergistic Effect of Platelet-Rich Plasma and Stem Cell-Seeded Hydrogel for Healing of Rat Chronic Rotator Cuff Injuries.

Outcomes after repair of chronic rotator cuff injuries remain suboptimal. Type-1 collagen-rich tendon hydrogel was previously reported to improve healing in a rat chronic rotator cuff injury model. Stem cell seeding of the tendon hydrogel improved bone quality in the same model. This study aimed to examine whether there was a synergistic and dose-dependent effect of platelet-rich plasma (PRP) on tendon-bone interface healing by combining PRP with stem cell-seeded tendon hydrogel. Human cadaveric tendons were processed into a hydrogel. PRP was prepared at two different platelet concentrations: an initial concentration (initial PRP group) and a higher concentration (concentrated PRP group). Tendon hydrogel was mixed with adipose-derived stem cells and one of the platelet concentrations. Methylcellulose, as opposed to saline, was used as a negative control due to comparable viscosity. The supraspinatus tendon was detached bilaterally in 33 Sprague-Dawley rats (66 shoulders). Eight weeks later, each detached tendon was repaired, and a hydrogel mixture or control was injected at the repair site. Eight weeks after repair, shoulder samples were harvested and assigned for biomechanical testing (n = 42 shoulders) or a combination of bone morphological and histological assessment (n = 24 shoulders). Biomechanical testing showed significantly higher failure load and stiffness in the concentrated PRP group than in control. Yield load in the initial and concentrated PRP groups were significantly higher than that in the control. There were no statistically significant differences between the initial and concentrated PRP groups. The addition of the highly concentrated PRP to stem cells-seeded tendon hydrogel improved healing biomechanically after chronic rotator cuff injury in rats compared to control. However, synergistic and dose-dependent effects were not seen.

Topical Antibiotic Elution in a Collagen-Rich Hydrogel Successfully Inhibits Bacterial Growth and Biofilm Formation In Vitro.

Chronic wounds are a prominent concern, accounting for $25 billion of health care costs annually. Biofilms have been implicated in delayed wound closure, but they are susceptible to developing antibiotic resistance and treatment options continue to be limited. A novel collagen-rich hydrogel derived from human extracellular matrix presents an avenue for treating chronic wounds by providing appropriate extracellular proteins for healing and promoting neovascularization. Using the hydrogel as a delivery system for localized secretion of a therapeutic dosage of antibiotics presents an attractive means of maximizing delivery while minimizing systemic side effects. We hypothesize that the hydrogel can provide controlled elution of antibiotics leading to inhibition of bacterial growth and disruption of biofilm formation. The rate of antibiotic elution from the collagen-rich hydrogel and the efficacy of biofilm disruption was assessed with Pseudomonas aeruginosa Bacterial growth inhibition, biofilm disruption, and mammalian cell cytotoxicity were quantified using in vitro models. The antibiotic-loaded hydrogel showed sustained release of antibiotics for up to 24 h at therapeutic levels. The treatment inhibited bacterial growth and disrupted biofilm formation at multiple time points. The hydrogel was capable of accommodating various classes of antibiotics and did not result in cytotoxicity in mammalian fibroblasts or adipose stem cells. The antibiotic-loaded collagen-rich hydrogel is capable of controlled antibiotic release effective for bacteria cell death without native cell death. A human-derived hydrogel that is capable of eluting therapeutic levels of antibiotic is an exciting prospect in the field of chronic wound healing.