The field of biodegradable synthetic polymers, which
is central
for regenerative engineering and drug delivery applications, encompasses
a multitude of hydrolytically sensitive macromolecular structures
and diverse processing approaches. The ideal degradation behavior
for a specific life science application must comply with a set of
requirements, which include a clinically relevant kinetic profile,
adequate biocompatibility, benign degradation products, and controlled
structural evolution. Although significant advances have been made
in tailoring materials characteristics to satisfy these requirements,
the impacts of autocatalytic reactions and microenvironments are often
overlooked resulting in uncontrollable and unpredictable outcomes.
Therefore, roles of surface versus bulk erosion, in situ microenvironment, and autocatalytic mechanisms should be understood
to enable rational design of degradable systems. In an attempt to
individually evaluate the physical state and form factors influencing
autocatalytic hydrolysis of degradable polymers, this Review follows
a hierarchical analysis that starts with hydrolytic degradation of
water-soluble polymers before building up to 2D-like materials, such
as ultrathin coatings and capsules, and then to solid-state degradation.
We argue that chemical reactivity largely governs solution degradation
while diffusivity and geometry control the degradation of bulk materials,
with thin “2D” materials remaining largely unexplored.
Following this classification, this Review explores techniques to
analyze degradation in vitro and in vivo and summarizes recent advances toward understanding degradation
behavior for traditional and innovative polymer systems. Finally,
we highlight challenges encountered in analytical methodology and
standardization of results and provide perspective on the future trends
in the development of biodegradable polymers.