Biomedical Engineering Reference
In-Depth Information
VEGF, VEGFR-2, and NRP-1, and this ultimately enhances the effectiveness
of signal transduction [22, 24, 26]. The importance of ECM components in
VEGFR signaling is further emphasized by the finding that VEGF121 appears
to elicit reduced biologic potency relative to the ECM-binding isoforms [24].
Biomimicry of the ECM's sustained release properties is critical to the ther-
apeutic success of polymeric systems for VEGF delivery. Specifically, recre-
ation of the physiological ECM binding characteristics may result in ways to
stabilize incorporated VEGF, present it in a localized fashion, and improve its
signaling capacity.
3
Bioinspired Polymer Delivery Strategies
The main goal of polymeric VEGF delivery systems is controlling the lo-
calized and sustained availability of the growth factor. Towards this end,
investigation of the physicochemical properties of the delivery vehicle has
been the focus of most research to date. Over the last few years, however, an
improved understanding of VEGF biology has made it clear that it is not suffi-
cient to only equip VEGF delivery systems with appropriate physicochemical
properties, but also that it may be necessary to mimic certain physiological
signaling events. Appropriate design of polymeric vehicles in the context of
the local biology may result in advanced, bioinspired delivery systems that
improve tissue regeneration. In addition, independent from the application,
VEGF delivery systems should readily incorporate into the defect site while
not compromising the remaining tissue functions or limiting the body's in-
trinsic regenerative capacity.
3.1
Biological Design Attributes
The properties specifically demanded from the system are prescribed by the
characteristics of the tissue to be treated. For example, chronic degenerative
diseases such as neurologic diseases and osteoporosis may require continu-
ous delivery of VEGF over a prolonged period of time (months or years) [27],
whereas in acute cases of tissue damage (e.g., myocardial infarction or bone
fracture) VEGF may prove most beneficial if made bioavailable during a time
frame of days or weeks [28, 29]. Furthermore, the spatial dimensions of the
devices may vary significantly for different applications. Specifically, slowly
progressing, degenerative diseases (e.g., Alzheimer's or Parkinson's disease)
not associated with large lesions in early stages of the disease, may be treated
with relatively small VEGF delivery devices. In contrast, acute and oftentimes
large defects resulting from accidents or tissue resections may require bulkier
delivery vehicles that temporarily fill gaps and maintain sufficient space and
