An official website of the United States government
Functional repair of osteochondral (OC) tissue remains challenging because the transition from bone to cartilage presents gradients in biochemical and physical properties necessary for joint function. Osteochondral regeneration requires strategies that restore the spatial composition and organization found in the native tissue. Several biomaterial approaches have been developed to guide chondrogenic and osteogenic differentiation of human mesenchymal stem cells (hMSCs). These strategies can be combined with 3D printing, which has emerged as a useful tool to produce tunable, continuous scaffolds functionalized with bioactive cues. However, functionalization often includes one or more post-fabrication processing steps, which can lead to unwanted side effects and often produce biomaterials with homogeneously distributed chemistries. To address these challenges, surface functionalization can be achieved in a single step by solvent-cast 3D printing peptide-functionalized polymers. Peptide-poly(caprolactone) (PCL) conjugates were synthesized bearing hyaluronic acid (HA)-binding (HAbind–PCL) or mineralizing (E3–PCL) peptides, which have been shown to promote hMSC chondrogenesis or osteogenesis, respectively. This 3D printing strategy enables unprecedented control of surface peptide presentation and spatial organization within a continuous construct. Scaffolds presenting both cartilage-promoting and bone-promoting peptides had a synergistic effect that enhanced hMSC chondrogenic and osteogenic differentiation in the absence of differentiation factors compared to scaffolds without peptides or only one peptide. Furthermore, multi-peptide organization significantly influenced hMSC response. Scaffolds presenting HAbind and E3 peptides in discrete opposing zones promoted hMSC osteogenic behavior. In contrast, presenting both peptides homogeneously throughout the scaffolds drove hMSC differentiation towards a mixed population of articular and hypertrophic chondrocytes. These significant results indicated that hMSC behavior was driven by dual-peptide presentation and organization. The downstream potential of this platform is the ability to fabricate biomaterials with spatially controlled biochemical cues to guide functional tissue regeneration without the need for differentiation factors.
more »
« less
Solvent‐cast 3D printing with molecular weight polymer blends to decouple effects of scaffold architecture and mechanical properties on mesenchymal stromal cell fate
Abstract The biochemical and physical properties of a scaffold can be tailored to elicit specific cellular responses. However, it is challenging to decouple their individual effects on cell‐material interactions. Here, we solvent‐cast 3D printed different ratios of high and low molecular weight (MW) poly(caprolactone) (PCL) to fabricate scaffolds with significantly different stiffnesses without affecting other properties. Ink viscosity was used to match processing conditions between inks and generate scaffolds with the same surface chemistry, crystallinity, filament diameter, and architecture. Increasing the ratio of low MW PCL resulted in a significant decrease in modulus. Scaffold modulus did not affect human mesenchymal stromal cell (hMSC) differentiation under osteogenic conditions. However, hMSC response was significantly affected by scaffold stiffness in chondrogenic media. Low stiffness promoted more stable chondrogenesis whereas high stiffness drove hMSC progression toward hypertrophy. These data illustrate how this versatile platform can be used to independently modify biochemical and physical cues in a single scaffold to synergistically enhance desired cellular response.
more »
« less
- PAR ID:
- 10486676
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Biomedical Materials Research Part A
- Volume:
- 112
- Issue:
- 9
- ISSN:
- 1549-3296
- Format(s):
- Medium: X Size: p. 1364-1375
- Size(s):
- p. 1364-1375
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Electrospun fibrous scaffolds made from polymers such as polycaprolactone (PCL) have been used in drug delivery and tissue engineering for their viscoelasticity, biocompatibility, biodegradability, and tunability. Hydrophobicity and the prolonged degradation of PCL causes inhibition of the natural tissue-remodeling processes. Poliglecaprone (PGC), which consists of PCL and Poly (glycolic acid) (PGA), has better mechanical properties and a shorter degradation time compared to PCL. A blend between PCL and PGC called PPG can give enhanced shared properties for biomedical applications. In this study, we fabricated a blend of PCL and PGC nanofibrous scaffold (PPG) at different ratios of PGC utilizing electrospinning. We studied the physicochemical and biological properties, such as morphology, crystallinity, surface wettability, degradation, surface functionalization, and cellular compatibility. All PPG scaffolds exhibited good uniformity in fiber morphology and improved mechanical properties. The surface wettability and degradation studies confirmed that increasing PGC in the PPG composites increased hydrophilicity and scaffold degradation respectively. Cell viability and cytotoxicity results showed that the scaffold with PGC was more viable and less toxic than the PCL-only scaffolds. PPG fibers were successfully coated with polydopamine (PDA) and collagen to improve degradation, biocompatibility, and bioactivity. The nanofibrous scaffolds synthesized in this study can be utilized for tissue engineering applications such as for regeneration of human articular cartilage regeneration and soft bones.more » « less
-
Additive manufacturing has been used to develop a variety of scaffold designs for clinical and industrial applications. Mechanical properties (i.e., compression, tension, bending, and torsion response) of these scaffolds are significantly important for load-bearing orthopaedic implants. In this study, we designed and additively manufactured porous metallic biomaterials based on two different types of triply periodic minimal surface structures (i.e., gyroid and diamond) that mimic the mechanical properties of bone, such as porosity, stiffness, and strength. Physical and mechanical properties, including compressive, tensile, bending, and torsional stiffness and strength of the developed scaffolds, were then characterised experimentally and numerically using finite element method. Sheet thickness was constant at 300 μm, and the unit cell size was varied to generate different pore sizes and porosities. Gyroid scaffolds had a pore size in the range of 600–1200 μm and a porosity in the range of 54–72%, respectively. Corresponding values for the diamond were 900–1500 μm and 56–70%. Both structure types were validated experimentally, and a wide range of mechanical properties (including stiffness and yield strength) were predicted using the finite element method. The stiffness and strength of both structures are comparable to that of cortical bone, hence reducing the risks of scaffold failure. The results demonstrate that the developed scaffolds mimic the physical and mechanical properties of cortical bone and can be suitable for bone replacement and orthopaedic implants. However, an optimal design should be chosen based on specific performance requirements.more » « less
-
Abstract Engineered composite scaffolds composed of natural and synthetic polymers exhibit cooperation at the molecular level that closely mimics tissue extracellular matrix's (ECM) physical and chemical characteristics. However, due to the lack of smooth intermix capability of natural and synthetic materials in the solution phase, bio‐inspired composite material development has been quite challenged. In this research, we introduced new bio‐inspired material blending techniques to fabricate nanofibrous composite scaffolds of chitin nanofibrils (CNF), a natural hydrophilic biomaterial and poly (ɛ‐caprolactone) (PCL), a synthetic hydrophobic‐biopolymer. CNF was first prepared by acid hydrolysis technique and dispersed in trifluoroethanol (TFE); and second, PCL was dissolved in TFE and mixed with the chitin solution in different ratios. Electrospinning and spin‐coating technology were used to form nanofibrous mesh and films, respectively. Physicochemical properties, such as mechanical strength, and cellular compatibility, and structural parameters, such as morphology, and crystallinity, were determined. Toward the potential use of this composite materials as a support membrane in blood–brain barrier application (BBB), human umbilical vein endothelial cells (HUVECs) were cultured, and transendothelial electrical resistance (TEER) was measured. Experimental results of the composite materials with PCL/CNF ratios from 100/00 to 25/75 showed good uniformity in fiber morphology and suitable mechanical properties. They retained the excellent ECM‐like properties that mimic synthetic‐bio‐interface that has potential application in biomedical fields, particularly tissue engineering and BBB applications.more » « less
-
Biomedical_Engineering_Society (Ed.)Synthetic polymers have contributed significantly to the development of advanced scaffolds for load bearing tissue engineering applications. Despite this, there is still a need to create scaffolds that can simultaneously present multiple biophysical and biochemical properties to better mimic native cellular environments. Polyglycidol has been shown to be a biocompatible polyether polyol, that forms different, sometimes complex, polymeric architectures. Furthermore, it has multiple hydroxyl groups that are capable of numerous chemical modifications. However, little is known about the biocompatibility of modified polyglycidols and their resulting 3-D network. The overarching hypothesis for this project is that changes in the mechanical, structural, and compositional cues within a polyglycidol-based network can be tailored to influence cell responses. Therefore, as a crucial first step, we investigated the biocompatibility of functionalized polyglycidols, and the swelling, degradation, and mechanical properties of polyglycidol based hydrogels. Ongoing studies aim to show that a defined subset of biophysical and biochemical cues can be incorporated simultaneously within the polyglycidol hydrogel. Such an advanced scaffold would allow us to study the synergistic effects of various chemical and physical cues on cellular behavior.more » « less
