Strategies to refine the degradation behavior of polyester biomaterials, particularly to overcome the limitations of slow hydrolytic degradation, would broaden their utility. Herein, we examine the complexities of polyester degradation behavior, its assessment and strategies for refinement. The factors governing polyester degradation are strikingly complex. In addition to the half-life of the hydrolytically-labile bond, a series of interdependent material properties must be considered. Thus, methods used to characterize such material properties, both before and during degradation, must be carefully selected. Assessment of degradation behavior is further complicated by the variability of reported test protocols and the need for accelerated rather than real-time in vitro testing conditions. Ultimately, through better control of degradation behavior and correlation of in vitro, simulated degradation to that observed in vivo, the development of superior devices prepared with polyester biomaterials may be achieved.
Current clinical management of vocal fold (VF) scarring produces inconsistent and often suboptimal results. Researchers are investigating a number of alternative treatments for VF lamina propria (LP) scarring, including designer implant materials for functional LP regeneration. In the present study, we investigate the effects of the initial scaffold elastic modulus and mesh size on encapsulated VF fibroblast (VFF) extracellular matrix (ECM) production toward rational scaffold design. Polyethylene glycol diacrylate (PEGDA) hydrogels were selected for this study since their material properties, including mechanical properties, mesh size, degradation rate and bioactivity, can be tightly controlled and systematically modified. Porcine VFF were encapsulated in four PEGDA hydrogels with degradation half lives of ~25 days and initial elastic compressive moduli ranging from ~30 to 100 kPa and initial mesh sizes ranging from ~9 to 27 nm. After 30 days of static culture, VFF ECM production and phenotype in each formulation was assessed biochemically and histologically. Sulfated glycosaminoglycan synthesis increased in similar degree with both increasing initial modulus and decreasing initial mesh size. In contrast, elastin production decreased with increasing initial modulus but increased with decreasing initial mesh size. Both collagen deposition and the induction of a myofibroblastic phenotype depended strongly on initial mesh size but appeared largely unaffected by variations in initial modulus. The present results indicate that scaffold mesh size warrants further investigation as a critical regulator of VFF ECM synthesis. Furthermore, this study validates a systematic and controlled approach for analyzing VFF response to scaffold properties, which should aid in rational scaffold selection/design.
Toward improving implantable medical devices as well as diagnostic performance, the development of polymeric biomaterials having resistance to proteins remains a priority. Herein, we highlight key strategies reported in the recent literature that have relied upon improvement of surface hydrophilicity via direct surface modification methods or with bulk modification using surface modifying additives (SMAs). These approaches have utilized a variety of techniques to incorporate the surface hydrophilization agent, including physisorption, hydrogel network formation, surface grafting, layer-by-layer (LbL) assembly and blending base polymers with SMAs. While poly(ethylene glycol) (PEG) remains the gold standard, new alternatives have emerged such as polyglycidols, poly(2-oxazoline)s (POx), polyzwitterions, and amphiphilic block copolymers. While these new strategies provide encouraging results, the need for improved correlation between in vitro and in vivo protein resistance is critical. This may be achieved by employing complex protein solutions as well as strides to enhance the sensitivity of protein adsorption measurements.
Hydrogels are frequently used biomaterials due to their similarity in hydration and structure to biological tissues. However, their utility is limited by poor mechanical properties, namely, a lack of strength and stiffness that mimic that of tissues, particularly load-bearing tissues. Thus, numerous recent strategies have sought to enhance and tune these properties in hydrogels, including interpenetrating networks (IPNs), macromolecular cross-linking, composites, thermal conditioning, polyampholytes, and dual cross-linking. Individually, these approaches have achieved hydrogels with either high strength (σ f > 10 MPa), high stiffness (E > 1 MPa), or, less commonly, both high strength and stiffness (σ f > 10 MPa and E > 1 MPa). However, only certain unique combinations of these approaches have been able to synergistically achieve retention of a high, tissuelike water content as well as high strength and stiffness. Applying such methods to stimuliresponsive hydrogels has also produced robust, smart biomaterials. Overall, methods to achieve hydrogels that simultaneously mimic the hydration, strength, and stiffness of soft and load-bearing tissues have the potential to be used in a much broader range of biomedical applications.
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