Biological resurfacing of grade IV articular cartilage ulcers in knee joint with Hyalofast

Introduction: Hyalofast grafting with microfracture is a new minimally invasive treatment method being proposed for joint cartilage defects. This study was done to measure the clinical efficacy of Hyalofast grafting after microfractures. Methods: Forty-six patients were assessed for knee function using knee injury and osteoarthritis outcome score (KOOS) after undergoing microfracture and Hyalofast grafting surgery. We further divided the 46 patients into a group of 10 patients who had no associated procedures done with the microfracture and Hyalofast grafting surgery. All patients had magnetic resonance imaging (MRI) of the affected knee pre-surgery and two patients had MRI done post-surgery. Due to another unrelated injury, we were also able to obtain further arthroscopic findings of another patient’s knee 18 months after microfracture and Hyalofast grafting. Results: There was a statistically significant improvement in all categories of the KOOS (symptoms, pain, daily living, sports and quality of life) compared between years 1, 2 and 3 against pre-surgery. For the subgroup of Hyalofast only, there was a statistically significant improvement in symptoms, pain and daily living categories of the KOOS compared between years 1, 2 and 3 against pre-surgery. Conclusions: Our study shows that Hyalofast grafting after microfracture is a viable alternative to treatment for patients with grade 4 cartilage ulcers.

Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing

Biological resurfacing of entire articular surfaces represents an important but challenging strategy for treatment of cartilage degeneration that occurs in osteoarthritis. Not only does this approach require anatomically sized and functional engineered cartilage, but the inflammatory environment within an arthritic joint may also inhibit chondrogenesis and induce degradation of native and engineered cartilage. The goal of this study was to use adult stem cells to engineer anatomically shaped, functional cartilage constructs capable of tunable and inducible expression of antiinflammatory molecules, specifically IL-1 receptor antagonist (IL-1Ra). Large (22-mm-diameter) hemispherical scaffolds were fabricated from 3D woven poly(ε-caprolactone) (PCL) fibers into two different configurations and seeded with human adipose-derived stem cells (ASCs). Doxycycline (dox)-inducible lentiviral vectors containing eGFP or IL-1Ra transgenes were immobilized to the PCL to transduce ASCs upon seeding, and constructs were cultured in chondrogenic conditions for 28 d. Constructs showed biomimetic cartilage properties and uniform tissue growth while maintaining their anatomic shape throughout culture. IL-1Ra–expressing constructs produced nearly 1 µg/mL of IL-1Ra upon controlled induction with dox. Treatment with IL-1 significantly increased matrix metalloprotease activity in the conditioned media of eGFP-expressing constructs but not in IL-1Ra–expressing constructs. Our findings show that advanced textile manufacturing combined with scaffold-mediated gene delivery can be used to tissue engineer large anatomically shaped cartilage constructs that possess controlled delivery of anticytokine therapy. Importantly, these cartilage constructs have the potential to provide mechanical functionality immediately upon implantation, as they will need to replace a majority, if not the entire joint surface to restore function.