(4a) 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.

https://proceedings.aiche.org/sites/default/files/aiche-proceedings/con…" v:shapes="_x0000_s1026" height="514" class="documentimage">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.