Intrinsic osteoinductivity of PCL-DA/PLLA semi-IPN shape memory polymer scaffolds.
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ABSTRACT:
SUBMITTER: Arabiyat AS
PROVIDER: S-EPMC8736335 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A scaffold that is inherently bioactive, osteoinductive and osteoconductive may guide mesenchymal stem cells (MSCs) to regenerate bone tissue in the absence of exogenous growth factors. Previously, we established that hydrogel scaffolds formed by crosslinking methacrylated star poly(dimethylsiloxane) (PDMSstar-MA) with diacrylated poly(ethylene glycol) (PEG-DA) promote bone bonding by induction of hydroxyapatite formation ("bioactive") and promote MSC lineage progression toward osteoblast-like fate ("osteoinductive"). Herein, we have combined solvent induced phase separation (SIPS) with a fused salt template to create PDMSstar-PEG hydrogel scaffolds with controlled PDMSstar-MA distribution as well as interconnected macropores of a tunable size to allow for subsequent cell seeding and neotissue infiltration ("osteoconductive"). Scaffolds were prepared with PDMSstar-MA of two number average molecular weights (Mns) (2k and 7k) with varying PDMSstar-MA:PEG-DA ratios and template salt sizes. The distribution of PDMSstar-MA within the hydrogels was examined as well as pore size, percent interconnectivity, dynamic and static moduli, hydration, degradation and in vitro bioactivity (i.e. mineralization when exposed to simulated body fluid, SBF). Finally, cell culture with seeded human bone marrow-derived MSCs (hBMSCs) was used to confirm non-cytotoxicity and characterize osteoinductivity. Tunable, interconnected macropores were achieved by utilization of a fused salt template of a specified salt size during fabrication. Distribution of PDMSstar-MA within the PEG-DA matrix improved for the lower Mn and contributed to differences in specific material properties (e.g. local modulus) and cellular response. However, all templated SIPS PDMSstar-PEG hydrogels were confirmed to be bioactive, non-cytotoxic and displayed PDMSstar-MA dose-dependent osteogenesis. STATEMENT OF SIGNIFICANCE: A tissue engineering scaffold that can inherently guide mesenchymal stem cells (MSCs) to regenerate bone tissue without growth factors would be a more cost-effective and safe strategy for bone repair. Typically, glass/ceramic fillers are utilized to achieve this through their ability to induce hydroxyapatite formation ("bioactive") and promote MSC differentiation to an osteoblast-like fate ("osteoinductive"). Herein, we have fabricated an interconnected, macroporous PEG-DA hydrogel scaffold that utilizes PDMSstar-MA as a bioactive and osteoinductive scaffold component. We were able to show that these PDMSstar-PEG hydrogels maintain several key material characteristics for bone repair. Further, bioactivity and osteoinductivity were simultaneously achieved in human bone marrow-derived MSC culture, representing a notable achievement for an exclusively material-based strategy.
| S-EPMC6936328 | biostudies-literature
Project description:Accelerating the rate of polyester hydrolytic degradation is of interest for numerous biomedical applications. Poly(ε-caprolactone) (PCL) and poly(L-lactic acid) (PLLA) have been extensively studied as thermoplastic homo- and copolymers as well as PCL-PLLA blends. PCL-PLLA semi-interpenetrating networks (semi-IPN) prepared with thermoplastic PLLA embedded in a cross-linked PCL diacrylate (PCL-DA) network were previously shown to exhibit uniquely accelerated degradation behavior that increased with PLLA content. Herein, their properties before and during degradation were further investigated to reveal the origin of this behavior and to better understand the semi-IPNs' degradation mechanism. Initially, semi-IPNs exhibited restricted spherulite size and irregularity, as well as a phase-separated morphology and PLLA-rich surface. Under accelerated conditions (1 M NaOH, 37 °C), degradation was revealed to be initiated in PLLA regions. It was also found that the PCL-DA crosslinking and PCL-PLLA phase separation played the largest roles in degradation rates and that semi-IPNs underwent faster rates of degradation than an analogous blend largely due to the reduced crystallinity of PCL-DA. Non-accelerated conditions (PBS [pH = 7.4], 37 °C) up to 56 weeks, which had never before been studied for polyester semi-IPNs, revealed similar trends in degradation rates.
| S-EPMC6801114 | biostudies-literature
Project description:The utility of poly(ε-caprolactone) (PCL) as a shape memory polymer (SMP) may be improved by accelerating its degradation. Recently, we have reported novel semi-interpenetrating networks (semi-IPNs) composed of cross-linked PCL diacrylate (PCL-DA) and thermoplastic poly(l-lactic acid) (PLLA) that exhibited SMP behavior, accelerated degradation, and enhanced moduli versus the PCL-DA control. Herein, we systematically varied the thermoplastic component of the PCL-based semi-IPNs, incorporating homo- and copolymers based on lactic acid of different Mn, hydrophilicity, and crystallinity. Specifically, semicrystalline PLLAs of different Mns (7.5, 15, 30, and 120 kDa) were explored as the thermoplastics in the semi-IPNs. Additionally, to probe crystallinity and hydrophilicity, amorphous (or nearly amorphous) thermoplastics of different hydrophilicities (PDLLA and PLGAs 85:15, 70:30, and 50:50, l-lactide:glycolide mole % ratio) were employed. For all semi-IPNs, the wt % ratio of the cross-linked PCL-DA to thermoplastic was 75:25. The nature of the thermoplastics was linked to semi-IPN miscibility and the trends in accelerated degradation rates.
| S-EPMC8742658 | biostudies-literature
Project description:Blends of poly (L-lactide) (PLLA) and poly (?-caprolactone) (PCL) with and without paclitaxel were prepared via solution casting. DSC analysis as well as SEM analysis of the PLLA/PCL blend solution cast films showed that these blends are all phase separated.%PLLA crystallinity was found to increase with increasing PCL content (up till 15 wt.%). The PCL phase is found to homogeneously disperse in the PLLA matrix as spherical domains where the pore diameters of the PCL domains significantly increased with increasing PCL content. The degradation profiles matched with the slower degrading component PCL rather than PLLA and also increasing PCL content of the blends increased the degradation rate relatively. The increased crystallinity of the PLLA phase with increasing PCL contents confirmed that the degradation occurred through PCL phase. Cell proliferation on PLLA/PCL blends showed that all these blends were suitable for the support of cellular growth. Apoptosis assay with the paclitaxel-loaded PLLA/PCL blends showed an increase in cell death throughout 7 days of incubation where the cell death was increased with increasing PCL contents. This was attributed to the faster release of paclitaxel which was at least partially affected by the faster degradation rate at increasing PCL contents. The paclitaxel release was shown to be degradation controlled in the initial stages followed by a faster diffusion-controlled release in the later stages. These polymer blends were found to be very suitable paclitaxel release agents for which the paclitaxel release times can be altered with the composition of the blend and the film thickness.
| S-EPMC3225542 | biostudies-literature
Project description:This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU), grew within a colloidal solution of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers A and E, respectively). This method, applied for the first time in Semi-Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a 20-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst-solvent combinations. Monomer E-based PHU exhibited higher Mw¯ than monomer A-based PHU (34.1 kDa and 16.4 kDa, respectively). Applying the enhanced methodology to prepare 10 multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating monomer E enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when monomer A was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.
| S-EPMC11013152 | biostudies-literature
Project description:A material-guided, regenerative approach to heal cranial defects requires a scaffold that cannot only achieve conformal fit into irregular geometries but also has bioactivity and suitable resorption rates. We have previously reported "self-fitting" shape-memory polymer (SMP) scaffolds based on poly(ε-caprolactone) diacrylate (PCL-DA) that shape recover to fill irregular defect geometries. However, PCL-DA scaffolds lack innate bioactivity and degrade very slowly. Polydimethylsiloxane (PDMS) has been shown to impart innate bioactivity and modify degradation rates when combined with organic cross-linked networks. Thus, this work reports the introduction of PDMS segments to form PCL/PDMS SMP scaffolds. These were prepared as co-matrices with three types of macromers to systematically alter PDMS content and cross-link density. Specifically, PCL90-DA was combined with linear-PDMS66-dimethacrylate (DMA) or 4-armed star-PDMS66-tetramethacrylate (TMA) macromers at 90:10, 75:25, and 60:40 wt % ratios. Additionally, a triblock macromer (AcO-PCL45-b-PDMS66-b-PCL45-OAc), having a 65:35 wt % ratio PCL/PDMS, was used. Scaffolds exhibited pore interconnectivity and uniform pore sizes and further maintained excellent shape-memory behavior. Degradation rates increased with PDMS content and reduced cross-link density, with phase separation contributing to this effect. Irrespective of PDMS content, all PCL/PDMS scaffolds exhibited the formation of carbonated hydroxyapatite (HAp) following exposure to simulated body fluid (SBF). While inclusion of PDMS expectedly reduced scaffold modulus and strength, mineralization increased these properties and, in some cases, to values exceeding or similar to the PCL-DA, which did not mineralize.
| S-EPMC8742657 | biostudies-literature
Project description:Low-intensity pulsed ultrasound (LIPUS), which has been previously reported to promote bone repair, is proposed to be a noninvasive form of therapy for the treatment of osteonecrosis. Bone fillers made from composite scaffolds have been demonstrated to be effective for preventing bone defects such as osteonecrosis. The present study aimed to investigate whether the application of LIPUS combined with bone morphogenetic protein-2 (BMP-2)-loaded poly-L-lactic acid/polylactic-co-glycolic acid/poly-?-caprolactone (PLLA/PLGA/PCL) composite scaffolds can improve recovery in a rat model of steroid-induced osteonecrosis of the femoral head (ONFH). BMP-2-loaded PLGA microspheres incorporated into PLLA/PLGA/PCL composite scaffolds were constructed. Bilateral femoral head LIPUS intervention was conducted in rats with steroid-induced ONFH. LIPUS intervention alone contributed to the alleviation of osteonecrosis, in addition to improving load-carrying capacity and accelerated bone formation, angiogenesis and differentiation. Subsequently, femoral head parameters and assessment of load-carrying capacity, bone formation-related factors, and angiogenesis- and differentiation-related factors were measured in rats with or without implanted BMP-2-loaded PLLA/PLGA/PCL composite scaffolds. LIPUS combined with the implantation of PLLA/PLGA/PCL composite scaffolds loaded with BMP-2 microspheres protected rats against steroid-induced ONFH and improved load-carrying capacity, bone formation, angiogenesis and differentiation. Together, these data support the use of BMP-2-loaded PLLA/PLGA/PCL composite scaffolds combined with LIPUS for ONFH as a potential alternative curative solution for treating bone diseases.
| S-EPMC7523288 | biostudies-literature
Project description:Mussel-derived nacre and pearl, which are natural composites composed CaCO3 platelets and interplatelet organic matrix, have recently gained interest due to their osteogenic potential. The crystal form of CaCO3 could be either aragonite or vaterite depending on the characteristics of mineralization template within pearls. So far, little attention has been paid on the different osteogenic capacities between aragonite and vaterite pearl. In the current work, aragonite or vaterite pearl powders were incorporated into poly-l-lactic acid (PLLA) scaffold as bio-functional fillers for enhanced osteogenesis. In intro results revealed that PLLA/aragonite scaffold possessed stronger stimulatory effect on SaOS-2 cell proliferation and differentiation, evidenced by the enhanced cell viability, alkaline phosphatase activity, collagen synthesis and gene expressions of osteogenic markers including osteocalcin, osteopotin and bone sialoprotein. The bone regeneration potential of various scaffolds was evaluated in vivo employing a rabbit critical-sized radial bone defect model. The X-ray and micro-CT results showed that significant bone regeneration and bridging were achieved in defects implanted with composite scaffolds, while less bone formation and non-bridging were found for pure PLLA group. Histological evaluation using Masson's trichrome and hematoxylin/eosin (H&E) staining indicated a typical endochondral bone formation process conducted at defect sites treated with composite scaffolds. Through three-point bending test, the limbs implanted with PLLA/aragonite scaffold were found to bear significantly higher bending load compared to other two groups. Together, it is suggested that aragonite pearl has superior osteogenic capacity over vaterite pearl and PLLA/aragonite scaffold can be employed as a potential bone graft for bone regeneration.
| S-EPMC7334395 | biostudies-literature
Project description:Microtia, frequently encountered in plastic surgery practice, is usually corrected by auricular reconstruction with prostheses or autologous cartilages. In recent decades, however, cartilage tissue engineering has been emerging as a promising alternative for its minimal invasion and low immunogenicity. As a critical factor for tissue engineering, scaffolds are expected to be sufficiently porous and stiff to facilitate chondrogenesis. In this work, we introduce novel poly-l-lactic acid (PLLA) porous microsphere-reinforced silk-based hybrid (SBH) scaffolds with a multihierarchical porous structure. The scaffolds are fabricated by embedding PLLA porous microspheres (PMs) into a blending matrix of silk fibroin (SF) and gelatin solution, followed by mixing with a degummed silk fiber mesh and freeze-drying process. Through adjusting the amount of PLLA PMs, the mechanical strength approximates to natural cartilage and also balanced physical properties were realized. Biological evaluations of SBH scaffolds, both in vitro and in vivo, were conducted and PM-free plain silk-based (PSB) scaffolds were applied as control. Overall, it suggests that the incorporation of PLLA PMs remarkably improves mechanical properties and the capability to promote chondrogenesis of SBH scaffolds, and that SBH scaffolds appear to be a promising construct for potential applications in auricular cartilage tissue engineering and relevant fields.
| S-EPMC7860514 | biostudies-literature
Project description:The authors present the preparation procedure and a computational model of a three-layered fibrous scaffold for prolonged drug release. The scaffold, produced by emulsion/sequential electrospinning, consists of a poly(D,L-lactic-co-glycolic acid) (PLGA) fiber layer sandwiched between two poly(ε-caprolactone) (PCL) layers. Experimental results of drug release rates from the scaffold are compared with the results of the recently introduced computational finite element (FE) models for diffusive drug release from nanofibers to the three-dimensional (3D) surrounding medium. Two different FE models are used: (1) a 3D discretized continuum and fibers represented by a simple radial one-dimensional (1D) finite elements, and (2) a 3D continuum discretized by composite smeared finite elements (CSFEs) containing the fiber smeared and surrounding domains. Both models include the effects of polymer degradation and hydrophobicity (as partitioning) of the drug at the fiber/surrounding interface. The CSFE model includes a volumetric fraction of fibers and diameter distribution, and is additionally enhanced by using correction function to improve the accuracy of the model. The computational results are validated on Rhodamine B (fluorescent drug l) and other hydrophilic drugs. Agreement with experimental results proves that numerical models can serve as efficient tools for drug release to the surrounding porous medium or biological tissue. It is demonstrated that the introduced three-layered scaffold delays the drug release process and can be used for the time-controlled release of drugs in postoperative therapy.
| S-EPMC7341868 | biostudies-literature