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Joint diseases, such as osteoarthritis, often require delivery of drugs to chondrocytes residing within the cartilage. However, intra‐articular delivery of drugs to cartilage remains a challenge due to their rapid clearance within the joint. This problem is further exacerbated by the dense and negatively charged cartilage extracellular matrix (ECM). Cationic nanocarriers that form reversible electrostatic interactions with the anionic ECM can be an effective approach to overcome the electrostatic barrier presented by cartilage tissue. For an effective therapeutic outcome, the nanocarriers need to penetrate, accumulate, and be retained within the cartilage tissue. Nanocarriers that adhere quickly to cartilage tissue after intra‐articular administration, transport through cartilage, and remain within its full thickness are crucial to the therapeutic outcome. To this end, we used ring‐opening polymerization to synthesize branched poly(l‐lysine) (BPL) cationic nanocarriers with varying numbers of poly(lysine) branches, surface charge, and functional groups, while maintaining similar hydrodynamic diameters. Our results show that the multivalent BPL molecules, including those that are highly branched (i.e., generation two), can readily adhere and transport through the full thickness of cartilage, healthy and degenerated, with prolonged intra‐cartilage retention. Intra‐articular injection of the BPL molecules in mouse knee joint explants and rat knee joints showed their localization and retention. In summary, this study describes an approach to design nanocarriers with varying charge and abundant functional groups while maintaining similar hydrodynamic diameters to aid the delivery of macromolecules to negatively charged tissues. [ABSTRACT FROM AUTHOR]

Current hydrogel or fabric patches for organ repair are generally not designed to conform to the complex mechanics of dynamic organs such as the lung or heart. This study presents a new, biocompatible and bilayered, hydrogel‐based patch platform, consisting of a non‐fouling top layer and a cell adhesive bottom layer, that caters to the anisotropic and auxetic characteristics of dynamic organs. Integrated computational and experimental studies are used to screen over 116 unique anisotropic‐auxetic architectures to establish design rules and tailor the patches to a broad range of target organ dynamics. The patches are then validated in ex vivo and in vivo animal models, where the auxetic patches outperformed non‐auxetic patches in conforming to the volumetric dilation‐contraction of dynamic organs. To further expand the functionality of the auxetic patch platform, novel hole‐filling auxetic patches are developed. These hole‐filling patches composited with fibrin robustly reduce pulmonary air leakage in rats with surgically induced lung puncture. This is the first demonstration of a rational patch design framework that features both anisotropic and auxetic properties to cater to a wide range of organ dynamics. These studies pave the way for future clinical development of biomimetic patches. [ABSTRACT FROM AUTHOR]

Encapsulation of therapeutic cells in a semipermeable device can mitigate the need for systemic immune suppression following cell transplantation by providing local immunoprotection while being permeable to nutrients, oxygen, and different cell‐secreted biomolecules. However, fibrotic tissue deposition around the device has been shown to compromise the long‐term function of the transplanted cells. Herein, a macroencapsulation device design that improves long‐term survival and function of the transplanted cells is reported. The device is comprised of a semipermeable chitosan pouch with a tunable reservoir and molecularly engineered interface. The chitosan pouch interface decorated with 1,12‐dodecanedioic acid (DDA), limits the cell adhesion and vigorous foreign body response while maintaining the barrier properties amenable to cell encapsulation. The device provides long‐term protection to the encapsulated human primary hepatocytes in the subcutaneous space of immunocompetent mice. The device supports the encapsulated cells for up to 6 months as evident from cell viability and presence of human specific albumin in circulation. Solutions that integrate biomaterials and interfacial engineering such as the one described here may advance development of easy‐to manufacture and retrievable devices for the transplantation of therapeutic cells in the absence of immunosuppression. [ABSTRACT FROM AUTHOR]