Intrinsic osteoinductivity of PCL‐DA/PLLA semi‐IPN shape memory polymer scaffolds

Abstract

Engineering osteoinductive, self‐fitting scaffolds offers a potential treatment modality to repair irregularly shaped craniomaxillofacial bone defects. Recently, we innovated on osteoinductive poly(ε‐caprolactone)‐diacrylate (PCL‐DA) shape memory polymers (SMPs) to incorporate poly‐L‐lactic acid (PLLA) into the PCL‐DA network, forming a semi‐interpenetrating network (semi‐IPN). Scaffolds formed from these PCL‐DA/PLLA semi‐IPNs display stiffnesses within the range of trabecular bone and accelerated degradation relative to scaffolds formed from slowly degrading PCL‐DA SMPs. Herein, we demonstrate for the first time that PCL‐DA/PLLA semi‐IPN SMP scaffolds show increased intrinsic osteoinductivity relative to PCL‐DA. We also confirm that application of a bioinspired polydopamine (PD) coating further improves the osteoinductive capacity of these PCL‐DA/PLLA semi‐IPN SMPs. In the absence of osteogenic supplements, protein level assessment of human mesenchymal stem cells (h‐MSCs) cultured in PCL‐DA/PLLA scaffolds revealed an increase in expression of osteogenic markers osterix, bone morphogenetic protein‐4 (BMP‐4), and collagen 1 alpha 1 (COL1A1), relative to PCL‐DA scaffolds and osteogenic medium controls. Likewise, the expression of runt‐related transcription factor 2 (RUNX2) and BMP‐4 was elevated in the presence of PD‐coating. In contrast, the chondrogenic and adipogenic responses associated with the scaffolds matched or were reduced relative to osteogenic medium controls, indicating that the scaffolds display intrinsic osteoinductivity.

Ultra‐High Modulus Hydrogels Mimicking Cartilage of the Human Body

“…Cytocompatibility: Human bone marrow derived mesenchymal stem cells (hBMSCs) (Texas A&M Institute for Regenerative Medicine) from one donor were cultured as previously reported. [68,69] Briefly, the cells were maintained in Minimum Essential Medium-𝛼 (𝛼-MEM, Gibco) supplemented with 10% MSC-qualified, heat-inactivated fetal bovine serum (FBS, Gibco) and 1X GlutaMAX (Gibco) in a 37 °C-5% CO 2 jacketed incubator. Twenty-four hour prior to seeding in 24-well plates for experimentation, 1% antibiotic solution (10 000 IU mL -1 penicillin, 10 000 μg mL -1 streptomycin) was added to the growth medium, serving as the experimental medium.…”

Methodology for performing biomechanical push-out tests for evaluating the osseointegration of calvarial defect repair in small animal models

“…Such scaffolds have been shown to exhibit interconnected pores (average size of ∼220 μm) and a compressive modulus of ∼23.8 MPa. All scaffolds were prepared with a cell adhesive peptide (RGD; 1 mM) and half of the scaffold specimens were coated with a bioactive polydopamine as previously reported [6] . Yielding 6 push-out test specimens each, defects were treated with (i) uncoated scaffolds, (ii) uncoated scaffolds pre-seeded with rat-derived bone marrow mesenchymal stem cells [ 6 , 7 ] (BMSCs; 35 k), (iii) coated scaffolds, and (iv) coated scaffolds pre-seeded cells.…”

Trends in bioactivity: inducing and detecting mineralization of regenerative polymeric scaffolds

“…89 We likewise applied a PDA coating to polyester SMP scaffolds, which resulted in enhanced osteogenic differentiation of hMSCs as well as HAp mineralization after SBF exposure. 90 Direct surface treatment of polymeric scaffolds has also been utilized to invoke bioactivity. 76,91 Plasma treatment, wherein an electric current passes through a gas (e.g., oxygen, argon, and ammonia), is a popular method.…”

“… 89 We likewise applied a PDA coating to polyester SMP scaffolds, which resulted in enhanced osteogenic differentiation of hMSCs as well as HAp mineralization after SBF exposure. 90 …”