Shape Memory Polymer Scaffolds Research Articles

Biocompatibility and Bone Regeneration by Shape Memory Polymer Scaffolds.

Biodegradable, shape memory polymer (SMP) scaffolds based on poly(ε-caprolactone) (PCL) offer unique advantages as a regenerative treatment strategy for critical-sized bone defects. In particular, a conformal fit may be achieved following exposure to warm saline, thereby improving osseointegration and regeneration. Advancing the clinical translation of these SMP scaffolds requires establishment of efficacy not only in non-loading models, but also load-bearing or load-sharing models. Thus, the present study evaluated the biocompatibility and bone regeneration potential of SMP scaffolds in a rabbit distal femoral condyle model. Two distinct SMP scaffold compositions were evaluated, a "PCL-only" scaffold formed from PCL-diacrylate (PCL-DA) and a semi-interpenetrating network (semi-IPN) formed from PCL-DA and poly(L-lactic acid) (PCL:PLLA). Semi-IPN PCL:PLLA scaffolds possess greater rigidity and faster rates of degradation versus PCL scaffolds. In vivo biocompatibility was assessed with a rat subcutaneous implantation model, whereas osseointegration was assessed with a 4 mm × 8 mm rabbit distal femoral condyle defect model. Both types of SMP scaffolds exhibited excellent biocompatibility marked by infiltration with fibrous tissue and a minimal inflammatory response. When implanted in the rabbit distal femur, both SMP scaffolds supported bone ingrowth. Collectively, these results demonstrate that the SMP scaffolds are biocompatible and integrate with adjacent host osseous tissues when implanted in vivo in a load-sharing environment. This study provides key proof-of-concept data necessary to proceed with large animal translational studies and clinical trials in human subjects.

Programming-via-spinning: Electrospun shape memory polymer fibers with simultaneous fabrication and programming

Porous shape memory polymer (SMP) scaffolds are promising ‘smart’ materials for potential use in a wide range of biomedical applications. Electrospinning provides an approach to produce fibrous SMP scaffolds to enhance their porosity, mass transfer, and flexibility. Here, we studied the effects of electrospinning parameters (rotating collector rotational speed and solvent) on shape memory and mechanical properties of a biostable thermoplastic polyurethane (PUr) SMP. Scanning electron microscopy confirmed that fiber diameter and tortuosity could be tuned using varied collector rotation speeds and/or solvents. Mechanical properties, including modulus, tensile strength, and ultimate elongation, were tuned independently of chemistry based on variations in fiber architectures. All scaffolds demonstrated shape memory properties. Additionally, due to strains that are trapped in the fibers during the electrospinning process, SMP fibers are programmed into a strained, temporary shape during the fabrication step. These fibers can be immediately triggered to recover to a non-strained primary shape after fabrication to reduce sample preparation time and complexity. As a proof-of-concept, bacterial protease-responsive SMPs were electrospun and exposed to S. aureus in programmed secondary shapes. Upon exposure to bacteria, these SMPs underwent shape recovery, which resulted in reduced bacterial attachment and biofilm formation. These materials could be employed as bacteria-responsive wound dressings in future work. Overall, electrospinning provides a valuable tool for tuning mechanical and shape memory properties independently from chemistry and for programming SMPs during fabrication to enable scale-up of electrospun SMP scaffolds.

Laser additive manufacturing of shape memory biopolymer bone scaffold: 3D conductive network construction and electrically driven mechanism

IntroductionThe electro-actuated shape memory polymer scaffold has gained increasing attentions on the utilization of minimally invasive surgery for bone defect repair, which requires to construct an efficient conductive network to accomplish electrical-to-thermal conversion from conductive fillers to the entire matrix evenly. ObjectivesIn this study, multiwall carbon nanotube (MWCNT) was convective self-assembled on the ZnO tetrapod (t-ZnO) template, where MWCNT was controlled to disperse uniformly and regulated to contact with each other effectively due to the immersion capillary force during the evaporation loss of the convective self-assembly process, leading to an interwoven layer on the t-ZnO surface. MethodsThe prepared t-ZnO@MWCNT assembly was embedded in the poly(L-lactic acid)/thermoplastic polyurethane (PLLA/TPU) scaffold fabricated via selective laser sintering to construct a 3D conductive MWCNT network for improving the electro-actuated shape memory properties. ResultsIt was observed that the interconnected MWCNT formed a 3D conductive network in the matrix without significant aggregation, which boosted the electrical-to-thermal properties of the scaffold, and the scaffold containing t-ZnO@MWCNT assembly possessed better electro-actuated shape memory properties with shape fixity of 98.0% and shape recovery of 98.8%. ConclusionThe scaffold exhibited improved electro-actuated shape memory properties and mechanical properties and the osteogenic inductivity was promoted with the combined effect of t-ZnO and electrical stimulation.

Enhanced degradation and bioactivity in polysiloxane-based shape memory polymer (SMP) scaffolds

“Self-fitting” shape memory polymer (SMP) scaffolds based on poly(ε-caprolactone) diacrylate (PCL-DA) have the potential to improve healing of irregular bone defects due to their capacity to fill complex geometries and to intrinsically support human mesenchymal stem cell (h-MSC) mediated osteogenesis. In prior work, the incorporation of polydimethylsiloxane dimethacrylate (PDMS-DMA) resulted in PCL/PDMS SMP scaffolds that successfully induced in vitro mineralization and accelerated degradation, the latter stemming from phase separation effects. Herein, analogous scaffolds were created with a more hydrophilic polysiloxane, polymethylhydrosiloxane dimethacrylate (PMHS-DMA). When compared to analogous PCL/PDMS scaffolds, the resulting PCL/PMHS scaffolds exhibited desirably faster rates of in vitro degradation and mineralization. In vitro analyses on RGDS [Arg-Gly-Asp-Ser]-modified PCL/PMHS confirmed their capacity to intrinsically support h-MSC bone marker expression with similar specificity and potency as RGDS-containing PCL scaffolds. However, cellular spreading was reduced on RGDS-modified PCL/PMHS scaffolds versus PCL and analogous PCL/PDMS scaffolds due to a decrease in surface-available cell adhesive peptide.

Thermo-Mechanical Characterization of 4D-Printed Biodegradable Shape-Memory Scaffolds Using Four-Axis 3D-Printing System.

This study was conducted on different models of biodegradable SMP (shape-memory polymer) scaffolds. A comparison was conducted utilizing a basic FDM (fused deposition modeling)/MEX (material extrusion) printer with a standard printing technique and a novel, modified, four-axis printing method with a PLA (poly lactic acid) polymer as the printing material. This way of making the 4D-printed BVS (biodegradable vascular stent) made it possible to achieve high-quality surfaces due to the difference in printing directions and improved mechanical properties-tensile testing showed a doubling in the elongation at break when using the four-axis-printed specimen compared to the regular printing, of 8.15 mm and 3.92 mm, respectfully. Furthermore, the supports created using this method exhibited a significant level of shape recovery following thermomechanical programming. In order to test the shape-memory effect, after the thermomechanical programming, two approaches were applied: one approach was to heat up the specimen after unloading it inside temperature chamber, and the other was to heat it in a warm bath. Both approaches led to an average recovery of the original height of 99.7%, while the in-chamber recovery time was longer (120 s) than the warm-bath recovery (~3 s) due to the more direct specimen heating in the latter case. This shows that 4D printing using the newly proposed four-axis printing is an effective, promising technique that can be used in the future to make biodegradable structures from SMP.

Development of Gelatin-Based Shape-Memory Polymer Scaffolds with Fast Responsive Performance and Enhanced Mechanical Properties for Tissue Engineering Applications.

Shape-memory polymers (SMPs) can be defined as a reversibly changing form through deformation and recovery by external stimuli. However, there remain application limitations of SMPs, such as complicated preparation processes and slow shape recovery. Here, we designed gelatin-based shape-memory scaffolds by a facile dipping method in tannic acid solution. The shape-memory effect of scaffolds was attributed to the hydrogen bond between gelatin and tannic acid, which acts as the net point. Moreover, gelatin (Gel)/oxidized gellan gum (OGG)/calcium chloride (Ca) was intended to induce faster and more stable shape-memory behavior through the introduction of a Schiff base reaction. The chemical, morphological, physicochemical, and mechanical properties of the fabricated scaffolds were evaluated, and those results showed that the Gel/OGG/Ca had improved mechanical properties and structural stability compared with other scaffold groups. Additionally, Gel/OGG/Ca exhibited excellent shape-recovery behavior of 95.8% at 37 °C. As a consequence, the proposed scaffolds can be fixed to the temporary shape at 25 °C in just 1 s and recovered to the original shape at 37 °C within 30 s, implying a great potential for minimally invasive implantation.

In-vitro and in-vivo studies of 4D printed shape memory scaffolds with bioactive fillers and coating for enhanced bone tissue regeneration

Bone tissue engineering is considered one of the pivotal treatments for bone defects in patients. However, the conventional strategies for repairing irregular and complex bone defects are highly unsatisfactory, and appropriate repairing of bone defects remains a challenge. In recent years, smart scaffolds integrated with multiple functions have emerged as promising alternatives for the treatment of various bone defects. In this study, 4D printed shape memory polymer (SMP) scaffolds containing bioactive fillers (hydroxyapatite and alendronate) and collagen–dexamethasone (Col–Dex) coating were fabricated, and their microstructures, porosity, mechanical properties, and biological functions were thoroughly investigated. The SMP scaffolds manufactured in this study could be programmed into temporary shapes of small sizes and then recovered to working sizes and shapes under an alternating magnetic field to fill bone defects. In addition, the biological studies including cytotoxicity tests, osteogenesis-related gene expressions, fluorescence staining imaging, and animal experiments demonstrated the effective biological activities and osteogenic effects of the 4D printed SMP scaffolds, with potential applications in bone tissue regeneration. In other words, the prepared 4D printed scaffolds with bioactive fillers and the Col–Dex coating will provide an efficient approach for personalized bone tissue repair as well as enhanced bone tissue regeneration.

Comparative evaluation of mesenchymal stromal cell growth and osteogenic differentiation on a shape memory polymer scaffold.

Trauma-induced, critical-size bone defects pose a clinical challenge to heal. Albeit autografts are the standard-of-care, they are limited by their inability to be shaped to various defect geometries and often incur donor site complications. Herein, the combination of a "self-fitting" shape memory polymer (SMP) scaffold and seeded mesenchymal stromal cells (MSCs) was investigated as an alternative. The porous SMP scaffold, prepared from poly(ε-caprolactone) diacrylate (PCL-DA) and coated with polydopamine, provided conformal shaping and cell adhesion. MSCs from five tissues, amniotic (AMSCs), chorionic tissue (CHSCs), umbilical cord (UCSCs), adipose (ADSCs), and bone marrow (BMSCs) were evaluated for viability, density, and osteogenic differentiation on the SMP scaffold. BMSCs exhibited the fastest increase in cell density by day 3, but after day 10, CHSCs, UCSCs, and ADSCs approached similar cell density. BMSCs also showed the greatest calcification among the cell types, followed closely by ADSCs, CHSCs and AMSCs. Alkaline phosphatase (ALP) activity peaked at day 7 for AMSCs, UCSCs, ADSCs and BMSCs, and at day 14 for CHSCs, which had the greatest overall ALP activity. Of all the cell types, only scaffolds cultured with ADSCs in osteogenic media had increased hardness and local modulus as compared to blank scaffolds after 21days of cell culture and osteogenic differentiation. Overall, ADSCs performed most favorably on the SMP scaffold. The SMP scaffold was able to support key cellular behaviors of MSCs and could potentially be a viable, regenerative alternative to autograft.

Suitability of EtO sterilization for polydopamine-coated, self-fitting bone scaffolds

Irregularly shaped craniomaxillofacial (CMF) defects may be advantageously treated by “self-fitting” shape memory polymer (SMP) scaffolds, namely those prepared from poly(ε-caprolactone)diacrylate (PCL-DA) networks and PCL-DA/poly(L-lactic acid) (PLLA) (75:25 wt%) semi-interpenetrating polymer networks (semi-IPNs). In addition to achieving good scaffold-tissue contact, a polydopamine (PD) coating can be leveraged to enhance bioactivity for improved osseointegration. Sterilization with ethylene oxide (EtO) represents a logical choice due to its low operating temperature and humidity. Herein, for the first time, the impact of EtO sterilization on the material properties of PD-coated SMP scaffolds was systematically assessed. Morphological features (i.e., pore size and pore interconnectivity), and in vitro bioactivity were preserved as were PCL crystallinity, PLLA crystallinity, and crosslinking. These latter features led to sustained shape memory properties, and compressive modulus. EtO-sterilized, PD-coated scaffolds displayed similar in vitro degradation behaviors versus analogous non-sterilized scaffolds. This included maintenance of compression modulus following 28 days of exposure to non-accelerated degradation conditions.

Evaluation of a self-fitting, shape memory polymer scaffold in a rabbit calvarial defect model

Self-fitting scaffolds prepared from biodegradable poly(ε-caprolactone)-diacrylate (PCL-DA) have been developed for the treatment of craniomaxillofacial (CMF) bone defects. As a thermoresponsive shape memory polymer (SMP), with the mere exposure to warm saline, these porous scaffolds achieve a conformal fit in defects. This behavior was expected to be advantageous to osseointegration and thus bone healing. Herein, for an initial assessment of their regenerative potential, a pilot in vivo study was performed using a rabbit calvarial defect model. Exogenous growth factors and cells were excluded from the scaffolds. Key scaffold material properties were confirmed to be maintained following gamma sterilization. To assess scaffold integration and neotissue infiltration along the defect perimeter, non-critically sized (d = 8 mm) bilateral calvarial defects were created in 12 New Zealand white rabbits. Bone formation was assessed at 4 and 16 weeks using histological analysis and micro-CT, comparing defects treated with an SMP scaffold (d = 9 mm x t = 1 or 2 mm) to untreated defects (i.e. defects able to heal without intervention). To further assess osseointegration, push-out tests were performed at 16 weeks and compared to defects treated with poly(ether ether ketone) (PEEK) discs (d = 8.5 mm x t = 2 mm). The results of this study confirmed that the SMP scaffolds were biocompatible and highly conducive to bone formation and ingrowth at the perimeter. Ultimately, this resulted in similar bone volume and surface area versus untreated defects and superior performance in push-out testing versus defects treated with PEEK discs. Statement of significanceCurrent treatments of craniomaxillofacial (CMF) bone defects include biologic and synthetic grafts but they are limited in their ability to form good contact with adjacent tissue. A regenerative engineering approach using a biologic-free scaffold able to achieve conformal fitting represents a potential “off-the-shelf” surgical product to heal CMF bone defects. Having not yet been evaluated in vivo, this study provided the preliminary assessment of the bone healing potential of self-fitting PCL scaffolds using a rabbit calvarial defect model. The study was designed to assess scaffold biocompatibility as well as bone formation and ingrowth using histology, micro-CT, and biomechanical push-out tests. The favorable results provide a basis to pursue establishing self-fitting scaffolds as a treatment option for CMF defects.

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

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.

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

Push-out tests are frequently used to evaluate the bone-implant interfacial strength of orthopedic implants, particularly dental and craniomaxillofacial applications. There currently is no standard method for performing push-out tests on calvarial models, leading to a variety of inconsistent approaches. In this study, fixtures and methods were developed to perform push-out tests in accordance with the following design objectives: (i) the system rigidly fixes the explanted calvarial sample, (ii) it minimizes lateral bending, (iii) it positions the defect accurately, and (iv) it permits verification of the coaxial alignment of the defect with the push-out rod. The fixture and method was first validated by completing push-out experiments on 30 explanted murine cranial caps and two explanted leporine cranial caps, all induced with bilateral sub-critical defects (5.0 mm and 8.0 mm nominal diameter for the murine and leporine models, respectively). Defects were treated with an autograft (i.e., excised tissue flap), a shape memory polymer (SMP) scaffold, or a PEEK implant. Additional validation was performed on 24 murine cranial caps induced with a single, unilateral critically-sized defect (8.0 mm nominal diameter) and treated with an autograft or a SMP scaffold.•A novel fixture was developed for performing push-out mechanical tests to characterize the strength of a bone-implant interface in calvarial defect repair.•The fixture uses a 3D printed vertical clamp with mating alignment component to fix the sample in place without inducing lateral bending and verify coaxial alignment of push-out rod with the defect.•The fixture can be scaled to different calvarial defect geometries as validated with 5.0 mm bilateral and 8.0 mm single diameter murine calvarial defect model and 8.0 mm bilateral leporine calvarial defect model.

Smart Porous Scaffold Promotes Peri-Implant Osteogenesis under the Periosteum.

Background: Adequate peri-implant bone mass and bone quality are essential factors to ensure the initial stability of the implant and success of implant operation. In clinical settings, the lack of bone mass often restricts the implant operation. In this study, we fabricated a smart porous scaffold with a shape memory function and investigated whether it could promote peri-implant osteogenesis under the periosteum. Methods: A porous shape memory polymer (SMP) scaffold was fabricated and its shape memory function, mechanical properties, and degradation rate were tested in vitro. Moreover, the scaffold was implanted in the mandible of rabbits to evaluate its efficacy to promote peri-implant osteogenesis in the periosteum and enhance the initial stability of the implant. Histological, micro-CT, and biomechanical analyses were carried out for further verification. Results: The SMP scaffold has a good shape memory function and biocompatibility in vitro. In vivo experiments demonstrated that the SMP scaffold could recover to its original shape after implantation to create a small gap in the periosteum. After 12 weeks, the scaffold was gradually replaced by a newly formed bone, and the stability of the implant increased when it implanted with the scaffold. Conclusion: The present study indicates that the SMP scaffolds have a good shape memory function and could enhance peri-implant bone formation under the periosteum. The SMP scaffold provides a clinical potential candidate for bone tissue engineering under the periosteum.

Porous shape memory scaffold of dextran and hydroxyapatite for minimum invasive implantation for bone tissue engineering applications.

Minimally invasive implantation of a porous scaffold of large volume into bone defect site remains a challenge. Scaffolds based on shape memory polymer (SMP) show potential to be delivered in the compact form via minimally invasive surgery. The present study chooses poly (ε-caprolactone)-diols (PCL-diols) as the SMP to cross-link carboxyl dextran via ester bonds together with particle leaching method to yield a porous SMP scaffold. The inner surfaces of porous SMP scaffold are then mineralized via in situ precipitation to yield mineralized porous SMP-hydroxyapatite (SMP-HA) scaffold. The porous SMP-HA scaffold possesses pore size of 400-500 μm, with HA particles uniformly distributed and orientationally aligned on the inner surfaces of scaffold. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) are carried out to identify the HA deposition. The phase transition temperature of the scaffold is adjusted to 38°C via changing the dosage of PCL (molecule weight: 2800) to endow the scaffold with shape deformation and fixed properties, as well as well-performed shape recovery property under body temperature. Bone marrow mesenchymal stem cells (BMSCs) adhere on the inner surfaces of SMP-HA scaffold, exhibiting larger spreading area when compared to cells adhered on SMP scaffold without HA, promoting its osteogenesis. In vivo degradation showed that the scaffold degrades completely after 6 months post-implantation. At the same time, significant tissue and capillary invasion indicated that the present porous SMP-HA scaffold hold great promise towards bone tissue engineering applications.

Shape memory materials promoting cell adhesion and tissue invasion towards the applications requiring minimally invasive implantation

Minimally invasive implantation of porous implants with large volume for in vivo filling proposes high requirements for material preparation. Porous scaffolds based on shape memory polymer (SMP) possess great potential for being delivered as the compact form via minimally invasive surgery. Here, poly (ε-caprolactone)-dienes (PCL-dienes) and crylic acid (AA) were polymerized and cross-linked to fabricate SMP scaffolds, the porous structure of which was created through particle leaching method. Three scaffolds, PAA-PCL20, PAA-PCL50 and PAA-PCL80 were fabricated with different content of PCL-dienes, possessing similar pore size (350 μm) and porosity (85%). PAA-PCL50 scaffold had a Tm of 38 °C, exhibiting shape fixing ability at room temperature and shape recovery ability at body temperature. All scaffolds showed limited interaction with cells. The cell adhesion rate of PAA-PCL50 scaffold was 55%, the highest among the three scaffolds. To promote cellular adhesion, PAA-PCL50 scaffold was mineralized via in situ precipitation, exhibiting CaP particles on the inner surfaces. The mineralized scaffold still exhibited well-performed deformation and shape memory ability, with higher cell adhesion rate (86%) and proliferation rate. In vivo implantation result indicated that the mineralized PAA-PCL50 scaffold better supported tissue invasion, holding a great promise to improve neo-tissue formation.

Shape memory activation can affect cell seeding of shape memory polymer scaffolds designed for tissue engineering and regenerative medicine.

The ability of a three-dimensional scaffold to support cell seeding prior to implantation is a critical criterion for many scaffold-based tissue engineering and regenerative medicine strategies. Shape memory polymer functionality may present important new opportunities and challenges in cell seeding, but the extent to which shape memory activation can positively or negatively affect cell seeding has yet to be reported. The goal of this study was to determine whether shape memory activation can affect cell seeding. The hypothesis was that shape memory activation of porous scaffolds during cell seeding can affect both the number of cells seeded in a scaffold and the distribution (in terms of average infiltration distance) of cells following seeding. Here, we used a porous shape memory foam scaffold programmed to expand when triggered to study cell number and average cell infiltration distance following shape memory activation. We found that shape memory activation can affect both the number of cells and the average cell infiltration distance. The effect was found to be a function of rate of shape change and scaffold pore interconnectivity. Magnitude of shape change had no effect. Only reductions in cell number and infiltration distance (relative to control and benchmark) were observed. The findings suggest that strategies for tissue engineering and regenerative medicine that involve shape memory activation in the presence of a cell-containing medium in vitro or in vivo should consider how recovery rate and scaffold pore interconnectivity may ultimately impact cell seeding.

On-command on/off switching of progenitor cell and cancer cell polarized motility and aligned morphology via a cytocompatible shape memory polymer scaffold.

Invitro biomaterial models have enabled advances in understanding the role of extracellular matrix (ECM) architecture in the control of cell motility and polarity. Most models are, however, static and cannot mimic dynamic aspects of invivo ECM remodeling and function. To address this limitation, we present an electrospun shape memory polymer scaffold that can change fiber alignment on command under cytocompatible conditions. Cellular response was studied using the human fibrosarcoma cell line HT-1080 and the murine mesenchymal stem cell line C3H/10T1/2. The results demonstrate successful on-command on/off switching of cell polarized motility and alignment. Decrease in fiber alignment causes a change from polarized motility along the direction of fiber alignment to non-polarized motility and from aligned to unaligned morphology, while increase in fiber alignment causes a change from non-polarized to polarized motility along the direction of fiber alignment and from unaligned to aligned morphology. In addition, the findings are consistent with the hypothesis that increased fiber alignment causes increased cell velocity, while decreased fiber alignment causes decreased cell velocity. On-command on/off switching of cell polarized motility and alignment is anticipated to enable new study of directed cell motility in tumor metastasis, in cell homing, and in tissue engineering.

Cold Plasma Reticulation of Shape Memory Embolic Tissue Scaffolds.

Polyurethane shape memory polymer (SMP) foams are proposed for use as thrombogenic scaffolds to improve the treatment of vascular defects, such as cerebral aneurysms. However, gas blown SMP foams inherently have membranes between pores, which can limit their performance as embolic tissue scaffolds. Reticulation, or the removal of membranes between adjacent foam pores, is advantageous for improving device performance by increasing blood permeability and cellular infiltration. This work characterizes the effects of cold gas plasma reticulation processes on bulk polyurethane SMP films and foams. Plasma-induced changes on material properties are characterized using scanning electron microscopy, uniaxial tensile testing, goniometry, and free strain recovery experiments. Device specific performance is characterized in terms of permeability, platelet attachment, and cell-material interactions. Overall, plasma reticulated SMP scaffolds show promise as embolic tissue scaffolds due to increased bulk permeability, retained thrombogenicity, and favorable cell-material interactions.

Osteogenic Capacity of Human Adipose-Derived Stem Cells is Preserved Following Triggering of Shape Memory Scaffolds.

Recent advances in shape memory polymers have enabled the study of programmable, shape-changing, cytocompatible tissue engineering scaffolds. For treatment of bone defects, scaffolds with shape memory functionality have been studied for their potential for minimally invasive delivery, conformal fitting to defect margins, and defect stabilization. However, the extent to which the osteogenic differentiation capacity of stem cells resident in shape memory scaffolds is preserved following programmed shape change has not yet been determined. As a result, the feasibility of shape memory polymer scaffolds being employed in stem cell-based treatment strategies remains unclear. To test the hypothesis that stem cell osteogenic differentiation can be preserved during and following triggering of programmed architectural changes in shape memory polymer scaffolds, human adipose-derived stem cells were seeded in shape memory polymer foam scaffolds or in shape memory polymer fibrous scaffolds programmed to expand or contract, respectively, when warmed to body temperature. Osteogenic differentiation in shape-changing and control scaffolds was compared using mineral deposition, protein production, and gene expression assays. For both shape-changing and control scaffolds, qualitatively and quantitatively comparable amounts of mineral deposition were observed; comparable levels of alkaline phosphatase activity were measured; and no significant differences in the expression of genetic markers of osteogenesis were detected. These findings support the feasibility of employing shape memory in scaffolds for stem cell-based therapies for bone repair.

Self-deploying shape memory polymer scaffolds for grafting and stabilizing complex bone defects: A mouse femoral segmental defect study

Treatment of complex bone defects places a significant burden on the US health care system. Current strategies for treatment include grafting and stabilization using internal metal plates/screws, intramedullary rods, or external fixators. Here, we introduce the use of shape memory polymer (SMP) materials for grafting and adjunct stabilization of segmental defects. Self-deploying SMP grafts and SMP sleeves capable of expanding and contracting, respectively, under intraoperative conditions were developed and evaluated in a mouse segmental defect model in vivo. Integration between grafts/sleeves and native bone was assessed using x-ray radiography, microcomputed tomography, and torsional mechanical testing. We found that SMP grafts were able to integrate with the native bone after 12 weeks, maintain defect stability, and provide torsional mechanical properties comparable to an allograft alone treatment; however no gross de novo bone formation was observed. SMP sleeves did not inhibit bony bridging at the margins, and limbs treated with a sleeve/allograft combination had torsional mechanical properties comparable to limbs treated with an allograft alone. In vitro torsional and bending tests suggest sleeves may provide additional torsional stability to defects. Incorporation of shape memory into synthetic bone graft substitutes and adjunct stabilization devices is anticipated to enhance functionality of synthetic materials employed in both applications.