(805h) Polydopamine-Coated PCL Shape Memory Polymer Foams for Bone Regeneration

Introduction: Scaffolds employed in bone regeneration must promote
new bone formation while forming a strong physical interface with (conforming
with and bonding to) adjacent bone tissue to promote osteointegration.  In the present
study, the osteoinductivity of a ?self-fitting?, polydopamine-coated shape
memory polymer (SMP) scaffold was evaluated. This SMP foam was fabricated by
photopolymerization of diacrylated poly(e-caprolactone)
(DAcPCL) followed by polydopamine coating. When treated with warm saline (T
> T_m of PCL), the compressed DAcPCL foam not only expands but is
in a softened state, which permits its manipulation and conformability along
irregular bone defect ?boundaries? thereby promoting osteointegration. A
polydopamine coating was selected due to its ability to maintain its integrity
under repeated scaffold deformation (in contrast to calcium phosphate coatings)
and due to recent literature indicating that polydopamine stimulates osteoblast
adhesion and matrix mineralization. Results from the current work demonstrate
that polydopamine coatings increase the osteogenic capacity of these SMP foams.

Materials and Methods: Fabrication of DAcPCL foams. Photosensitive DAcPCL macromers were formed into
open porous foams via solvent casting/particulate leaching (SCPL) technique
which increases pore interconnectivity versus traditional salt-leaching. Following
salt leaching, subsets of foams were coated with an aqueous dopamine chloride
solution for 16 h to allow spontaneous oxidative polymerization of dopamine on
pore walls. Construct Culture and Analysis. Coated and uncoated
DAcPCL foams were seeded with human bone-marrow derived MSCs (Lonza) at 1x10⁶
per cm³. The resulting constructs were cultured for 2 weeks in Growth
Medium (GM; DMEM with 10% MSC-qualified FBS) or Osteogenic Medium (OM) (GM
supplemented with 0.1 µM dexamethasone, 50 µg/ml L-ascorbic acid-2-phosphate,
10 mM β-glycerolphosphate). Gene expression was then analyzed relative to β-actin
using qRT-PCR. Total calcium deposition was quantified using the CPC liquid
color kit (Stanbio).

Results
and Discussion: The capacity of polydopamine-coated
foams to support MSC osteogenesis was analyzed following 2 weeks of culture. In
the absence of osteogenic media supplements, general upregulation of adipogenic
(pparγ), chondrogenic (sox9, aggrecan [ACAN]), and osteogenic (runx2,
osteocalcin [BGLAP]) markers was observed in the uncoated scaffolds relative to
initial (day zero) expression levels (p<0.05; Fig 1A). In contrast,
polydopamine-coated scaffolds did not promote chondrogenesis, although they
still stimulated adipogenesis in addition to osteogenesis. When foams were
cultured under conditions of ?enforced? osteogenic specificity (under OM
conditions), an increase in MSC expression of osteogenic markers (runx2, osteopontin
[SPP1]) was observed on polydopamine-coated scaffolds relative uncoated
controls (p< 0.023, Fig. 1B).  Polydopamine-coated foams were also
associated with a 3.2-fold increase in calcium deposition relative to uncoated
scaffolds (p = 0.04, Fig. 1C). Cumulatively, these results support the osteogenic
potential of polydopamine-coated DAcPCL foams.

Conclusions:
DAcPCL SMP foams have significant
potential as bone regeneration scaffolds due to their high porosity,
elastomeric (non-brittle) nature, and capacity to be inserted in conformal
contact with bone defect boundaries (promoting osteointegration). The present
studies indicate that coating these SMP foams with polydopamine increases the
osteoinductive capacity of these novel scaffolds.

Acknowledgements:
MH and MG acknowledge NIH funding.