Extracellular matrix particle-glycosaminoglycan composite hydrogels for regenerative medicine applications.

Tissue extracellular matrix (ECM) is a complex material made up of fibrous proteins and ground substance (glycosaminoglycans, GAGs) that are secreted by cells. ECM contains important biological cues that modulate cell behaviors, and it also serves as a structural scaffold to which cells can adhere. For clinical applications, where immune rejection is a constraint, ECM can be processed using decellularization methods intended to remove cells and donor antigens from tissue or organs, while preserving native biological cues essential for cell growth and differentiation. In this study, a decellularized ECM-based composite hydrogel was formulated by using modified GAGs that covalently bind tissue particles. These GAG-ECM composite hydrogels combine the advantages of solid decellularized ECM scaffolds and pepsin-digested ECM hydrogels by facilitating ECM hydrogel formation without a disruptive enzymatic digestion process. Additionally, engineered hydrogels can contain more than one type of ECM (from bone, fat, liver, lung, spleen, cartilage, or brain), at various concentrations. These hydrogels demonstrated tunable gelation kinetics and mechanical properties, offering the possibility of numerous in vivo and in vitro applications with different property requirements. Retained bioactivity of ECM particles crosslinked into this hydrogel platform was confirmed by the variable response of stem cells to different types of ECM particles with respect to osteogenic differentiation in vitro, and bone regeneration in vivo. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 147-159, 2018.

Biodynamic performance of hyaluronic acid versus synovial fluid of the knee in osteoarthritis.

Hyaluronic acid (HA), a natural biomaterial present in healthy joints but depleted in osteoarthritis (OA), has been employed clinically to provide symptomatic relief of joint pain. Joint movement combined with a reduced joint lubrication in osteoarthritic knees can result in increased wear and tear, chondrocyte apoptosis, and inflammation, leading to cascading cartilage deterioration. Therefore, development of an appropriate cartilage model that can be evaluated for its friction properties with potential lubricants in different conditions is necessary, which can closely resemble a mechanically induced OA cartilage. Additionally, a comparison of different models with and without endogenous lubricating surface zone proteins, such as PRG4 promotes a well-rounded understanding of cartilage lubrication. In this study, we present our findings on the lubricating effects of HA on different articular cartilage model surfaces in comparison to synovial fluid, a physiological lubricating biomaterial. The mechanical testings data demonstrated that HA reduced average static and kinetic friction coefficient values of the cartilage samples by 75% and 70%, respectively. Furthermore, HA mimicked the friction characteristics of freshly harvested natural synovial fluid throughout all tested and modeled OA conditions with no statistically significant difference. These characteristics led us to exclusively identify HA as an effective boundary layer lubricant in the technology that we develop to treat OA (Singh et al., 2014).

Enhanced lubrication on tissue and biomaterial surfaces through peptide-mediated binding of hyaluronic acid.

Lubrication is key for the efficient function of devices and tissues with moving surfaces, such as articulating joints, ocular surfaces and the lungs. Indeed, lubrication dysfunction leads to increased friction and degeneration of these systems. Here, we present a polymer-peptide surface coating platform to non-covalently bind hyaluronic acid (HA), a natural lubricant in the body. Tissue surfaces treated with the HA-binding system exhibited higher lubricity values, and in vivo were able to retain HA in the articular joint and to bind ocular tissue surfaces. Biomaterials-mediated strategies that locally bind and concentrate HA could provide physical and biological benefits when used to treat tissue-lubricating dysfunction and to coat medical devices.