Articular cartilage regeneration using acellular bioactive affinity-binding alginate hydrogel: A 6-month study in a mini-pig model of osteochondral defects

Background: Despite intensive research, regeneration of articular cartilage largely remains an unresolved medical concern as the clinically available modalities still suffer from long-term inconsistent data, relatively high failure rates and high prices of more promising approaches, such as cell therapy. In the present study, we aimed to evaluate the feasibility and long-term efficacy of a bilayered injectable acellular affinity-binding alginate hydrogel in a large animal model of osteochondral defects. Methods: The affinity-binding alginate hydrogel is designed for presentation and slow release of chondrogenic and osteogenic inducers (transforming growth factor-β1 and bone morphogenic protein 4, respectively) in two distinct and separate hydrogel layers. The hydrogel was injected into the osteochondral defects created in the femoral medial condyle in mini-pigs, and various outcomes were evaluated after 6 months. Results: Macroscopical and histological assessment of the defects treated with growth factor affinity-bound hydrogel showed effective reconstruction of articular cartilage layer, with major features of hyaline tissue, such as a glossy surface and cellular organisation, associated with marked deposition of proteoglycans and type II collagen. Microcomputed tomography showed incomplete bone formation in both treatment groups, which was nevertheless augmented by the presence of affinity-bound growth factors. Importantly, the physical nature of the applied hydrogel ensured its shear resistance, seamless integration and topographical matching to the surroundings and opposing articulating surface. Conclusions: The treatment with acellular injectable growth factor–loaded affinity-binding alginate hydrogel resulted in effective tissue restoration with major hallmarks of hyaline cartilage, shown in large animal model after 6-month follow-up. The translational potential of this article: This proof-of-concept study in a clinically relevant large animal model showed promising potential of an injectable acellular growth factor–loaded affinity-binding alginate hydrogel for effective repair and regeneration of articular hyaline cartilage, representing a strong candidate for future clinical development. Keywords: Affinity-binding alginate, Bone morphogenic protein 4, Hyaline cartilage, Osteochondral defect, Transforming growth factor-β

Spontaneous Coassembly of Biologically Active Nanoparticles via Affinity Binding of Heparin-Binding Proteins to Alginate-Sulfate

Controlled delivery of heparin-binding (HB) proteins represents a challenge in regenerative medicine strategies. Here, we describe the features of novel nanoparticles (NPs), spontaneously coassembled due to affinity interactions between HB proteins and the semisynthetic anionic polysaccharide, alginate-sulfate. The NPs efficiently encapsulated and protected the proteins from proteolysis. Injection of a combination of NPs encapsulating multiple therapeutic growth factors promoted effective and long-term tissue repair in animal models of severe ischemia (murine model of hindlimb ischemia and acute myocardial infarction in rats). This simple yet efficient NP fabrication method is amenable for clinical use