Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel biomaterial and stimulation of adjacent cartilage tissue development by mesenchymal stem cells. For translation to the joint environment, a chondroitin sulfate adhesive was applied to covalently bond and adhere the hydrogel to cartilage and bone tissue in articular defects. After preclinical testing in a caprine model, a pilot clinical study was initiated where the biomaterials system was combined with standard microfracture surgery in 15 patients with focal cartilage defects on the medial femoral condyle. Control patients were treated with microfracture alone. Magnetic resonance imaging showed that treated patients achieved significantly higher levels of tissue fill compared to controls. Magnetic resonance spin-spin relaxation times (T₂) showed decreasing water content and increased tissue organization over time. Treated patients had less pain compared with controls, whereas knee function [International Knee Documentation Committee (IKDC)] scores increased to similar levels between the groups over the 6 months evaluated. No major adverse events were observed over the study period. With further clinical testing, this practical biomaterials strategy has the potential to improve the treatment of articular cartilage defects.

Articular cartilage repair remains a significant and growing clinical challenge with the aging population. The native extracellular matrix (ECM) of articular cartilage is a 3D structure composed of proteinaceous fibers and a hydrogel ground substance that together provide the physical and biological cues to instruct cell behavior. Here we present fibrous scaffolds composed of poly(vinyl alcohol) and the biological cue chondroitin sulfate with fiber dimensions on the nanoscale for application to articular cartilage repair. The unique, low-density nature of the described nanofiber scaffolds allows for immediate cell infiltration for optimal tissue repair. The capacity for the scaffolds to facilitate cartilage-like tissue formation was evaluated in vitro. Compared with pellet cultures, the nanofiber scaffolds enhance chondrogenic differentiation of mesenchymal stems cells as indicated by increased ECM production and cartilage specific gene expression while also permitting cell proliferation. When implanted into rat osteochondral defects, acellular nanofiber scaffolds supported enhanced chondrogenesis marked by proteoglycan production minimally apparent in defects left empty. Furthermore, inclusion of chondroitin sulfate into the fibers enhanced cartilage-specific type II collagen synthesis in vitro and in vivo. By mimicking physical and biological cues of native ECM, the nanofiber scaffolds enhanced cartilaginous tissue formation, suggesting their potential utility for articular cartilage repair.

Light-induced material phase transitions enable the formation of shapes and patterns from the nano- to the macroscale. From lithographic techniques that enable high-density silicon circuit integration, to laser cutting and welding, light–matter interactions are pervasive in everyday materials fabrication and transformation. These noncontact patterning techniques are ideally suited to reshape soft materials of biological relevance. We present here the use of relatively low-energy ($<$ 2 nJ) ultrafast laser pulses to generate 2D and 3D multiscale patterns in soft silk protein hydrogels without exogenous or chemical cross-linkers. We find that high-resolution features can be generated within bulk hydrogels through nearly 1 cm of material, which is 1.5 orders of magnitude deeper than other biocompatible materials. Examples illustrating the materials, results, and the performance of the machined geometries in vitro and in vivo are presented to demonstrate the versatility of the approach. Significance In this paper we present results on 3D, multiscale laser machining of soft, transparent biomaterials suited for cellular growth and/or implantation. We use an ultrafast laser to generate high-resolution, 3D structures within the bulk of a transparent soft-biomaterial formulation that can support cell growth and allow cells to penetrate deep within the material. The structure is created by multiphoton absorption which, thanks to the clarity of the silk gels, is possible nearly 1 cm below the surface of the material. This depth represents an ∼10× improvement over other materials. The ability to create micrometer-scale voids over such a large volume has promising applications in the biomedical field and its efficacy was demonstrated both in vitro and in vivo.