Fiber-reinforced Scaffolds Research Articles

GelMA-catechol coated FeHAp nanorods functionalized nanofibrous reinforced bio-instructive and mechanically robust composite hydrogel scaffold for bone tissue engineering

Critical bone defects complicate tissue graft-based surgeries, raising healthcare expenditures and underscoring scaffold-based tissue-engineering strategies to support bone reconstruction. Our study highlighted that the phase-compatible combination of inorganic nanorods, nanofibers, and hydrogels is promising for developing biomimetic and cell-instructive scaffolds since the bone matrix is a porous organic/inorganic composite. In brief, methacrylated gelatin (GelMA) was reacted with dopamine to form catechol-modified GeLMA (GelMA-C). The GelMA-C was nanocoated onto an iron-doped hydroxyapatite (FeHAp) nanorod via metal-catechol network coordination. The modified nanorod (FeHAp@GelMA-C) was loaded onto GelMA-based nanofibers. The nanorods loaded pre-fibers were electrospun onto GelMA solution and photochemically crosslinked to fabricate a fiber-reinforced hydrogel. The structural, mechanical, physicochemical, biocompatibility, swelling properties, osteogenic potential, and bone remodelling potential (using rat femoral defect model) of modified nanorods, simple hydrogel, and nanorod-loaded fiber-reinforced hydrogel were studied. The results supported that the interface interaction between GelMA-C/nanorods, nanorods/nanofibers, nanorods/hydrogels, and nanofiber/hydrogels significantly improved the microstructural and mechanical properties of the scaffold. Compared to pristine hydrogel, the nanorod-loaded fiber-reinforced scaffold better supported cellular responses, osteogenic differentiation, matrix mineralization, and accelerated bone regeneration. The nanorod-loaded fiber-reinforced hydrogel proved more biomimetic and cell-instructive for guided bone reconstruction.

Bio-Inspired Fiber Reinforcement for Aortic Valves: Scaffold Production Process and Characterization.

The application of tissue-engineered heart valves in the high-pressure circulatory system is still challenging. One possible solution is the development of biohybrid scaffolds with textile reinforcement to achieve improved mechanical properties. In this article, we present a manufacturing process of bio-inspired fiber reinforcement for an aortic valve scaffold. The reinforcement structure consists of polyvinylidene difluoride monofilament fibers that are biomimetically arranged by a novel winding process. The fibers were embedded and fixated into electrospun polycarbonate urethane on a cylindrical collector. The scaffold was characterized by biaxial tensile strength, bending stiffness, burst pressure and hemodynamically in a mock circulation system. The produced fiber-reinforced scaffold showed adequate acute mechanical and hemodynamic properties. The transvalvular pressure gradient was 3.02 ± 0.26 mmHg with an effective orifice area of 2.12 ± 0.22 cm2. The valves sustained aortic conditions, fulfilling the ISO-5840 standards. The fiber-reinforced scaffold failed in a circumferential direction at a stress of 461.64 ± 58.87 N/m and a strain of 49.43 ± 7.53%. These values were above the levels of tested native heart valve tissue. Overall, we demonstrated a novel manufacturing approach to develop a fiber-reinforced biomimetic scaffold for aortic heart valve tissue engineering. The characterization showed that this approach is promising for an in situ valve replacement.

3D Fiber Reinforced Hydrogel Scaffolds by Melt Electrowriting and Gel Casting as a Hybrid Design for Wound Healing.

Emerging biomanufacturing technologies have revolutionized the field of tissue engineering by offering unprecedented possibilities. Over the past few years, new opportunities arose by combining traditional and novel fabrication techniques, shaping the hybrid designs in biofabrication. One of the potential application fields is skin tissue engineering, in which a combination of traditional principles of wound dressing with advanced biofabrication methods could yield more efficient therapies. In this study, a hybrid design of fiber-reinforced scaffolds combined with gel casting is developed and the efficiency for in vivo wound healing applications is assessed. For this purpose, 3D fiber meshes produced by melt electrowriting are selectively filled with photocrosslinkable gelatin hydrogel matrices loaded with different growth factor carrier microspheres. Additionally, the influence of the inclusion of inorganic bioactive glass particles within the composite fibrous mesh is evaluated. Qualitative evaluation of secondary wound healing criteria and histological analysis shows that hybrid scaffolds containing growth factors and bioactive glass enhances the healing process significantly, compared to the designs merely providing a fiber-reinforced bioactive hydrogel matrix as the wound dressing. This study aims to explore a new application area for melt electrowriting as a powerful tool in fabricating hybrid therapeutic designs for skin tissue engineering.

Personalized Fiber-Reinforcement Networks for Meniscus Reconstruction.

The menisci are fibrocartilaginous tissues that are crucial to the load-sharing and stability of the knee, and when injured, these properties are compromised. Meniscus replacement scaffolds have utilized the circumferential alignment of fibers to recapitulate the microstructure of the native meniscus; however, specific consideration of size, shape, and morphology has been largely overlooked. The purpose of this study was to personalize the fiber-reinforcement network of a meniscus reconstruction scaffold. Human cadaveric menisci were measured for a host of tissue (length, width) and subtissue (regional widths, root locations) properties, which all showed considerable variability between donors. Next, the asymmetrical fiber network was optimized to minimize the error between the dimensions of measured menisci and predicted fiber networks, providing a 51.0% decrease (p = 0.0091) in root-mean-square (RMS) error. Finally, a separate set of human cadaveric knees was obtained, and donor-specific fiber-reinforced scaffolds were fabricated. Under cyclic loading for load-distribution analysis, in situ implantation of personalized scaffolds following total meniscectomy restored contact area (253.0 mm2 to 488.9 mm2, p = 0.0060) and decreased contact stress (1.96 MPa to 1.03 MPa, p = 0.0025) to near-native values (597.4 mm2 and 0.83 MPa). Clinical use of personalized meniscus devices that restore physiologic contact stress distributions may prevent the development of post-traumatic osteoarthritis following meniscal injury.

Fiber-Reinforced Silk Composite for Enhanced Urokinase Production Using High-Density Perfusion Culture and Bioactive Molecule Supplementation.

Urokinase plasminogen activator (uPA) has been extensively used as a thrombolytic drug in cases of myocardial infarction, thromboembolism, and ischemic brain stroke. Media optimization and high-density perfusion culture are the decisive factors that facilitate enhanced urokinase production in a conditioned medium. In this study, we have aimed for a high-density perfusion culture of HT1080, a human fibrosarcoma cell line, by formulating optimal media for enhanced urokinase productivity. Four scaffold variants were fabricated from silk fibroin and microfibers of Bombyx mori (BM) and Antheraea assamensis (AA) and physico-chemically characterized. Field emission scanning electron microscopy studies revealed a heterogeneous distribution of pores with interconnected networks supporting cell infiltration, attachment, and long-term viability. AA-based fiber-reinforced scaffolds (ASAF) demonstrated superior mechanical strength, integral stability, and increased cell proliferation as compared to pure silk scaffolds. Media formulation was accomplished by limiting serum concentration (2% FBS) and supplementing with 20 μg/mL arginine and 20 ng/mL TGF-β1 to retain the stationary phase of cells and augment the urokinase production. A perfusion bioreactor culture of HT1080-laden scaffolds in the presence of formulated media was performed for improving the production of urokinase, with a maximum activity of 432 U/L. Also, gene expression analysis revealed that the individual silk scaffolds have different effects on regulating the expression of plasminogen activator urokinase and plasminogen activator urokinase receptor. In brief, our results suggest that a perfusion bioreactor culture of HT1080-laden ASAF scaffolds in formulated media promotes an increased urokinase production, such that it can be further used as a novel 3D matrix platform for industrial production of the lifesaving uPA drug.

Tissue-Engineered Total Meniscus Replacement With a Fiber-Reinforced Scaffold in a 2-Year Ovine Model

Background: Meniscus injuries and associated meniscectomies cause patients long-term pain and discomfort and can lead to joint deterioration. Purpose: To evaluate a collagen-hyaluronan sponge reinforced with synthetic resorbable polymer fiber for total meniscus reconstruction in a long-term ovine model. Study Design: Controlled laboratory study. Methods: Eleven skeletally mature sheep were implanted with the total meniscus scaffold. At 2 years, explants were evaluated biologically (radial/circumferential histology, immunofluorescence) and mechanically (compression, tension), and articular surfaces were examined for damage. Results: The fiber-reinforced scaffold induced formation of functional neomeniscus tissue that was intact in 8 of 11 animals. The implant was remodeled into organized circumferentially aligned collagen bundles to resist meniscus hoop stresses. Moreover, type II collagen and proteoglycan deposition near the inner margin suggested a direct response to compressive stresses and confirmed fibrocartilage formation. Cartilage damage was observed, but end-stage (severe) joint deterioration associated with meniscectomy was avoided, even with limitations regarding the ovine surgical procedure and postoperative care. Conclusion: A fiber-reinforced total meniscus replacement device induces formation of functional neomeniscus tissue that has the potential to prevent catastrophic joint deterioration associated with meniscectomy. Clinical Relevance: An off-the-shelf meniscus device that can be remodeled into functional tissue and thus prevent or delay the onset of osteoarthritis could address a widespread clinical need after meniscus injury.

Fiber-reinforced scaffolds in soft tissue engineering.

Soft tissue engineering has been developed as a new strategy for repairing damaged or diseased soft tissues and organs to overcome the limitations of current therapies. Since most of soft tissues in the human body are usually supported by collagen fibers to form a three-dimensional microstructure, fiber-reinforced scaffolds have the advantage to mimic the structure, mechanical and biological environment of natural soft tissues, which benefits for their regeneration and remodeling. This article reviews and discusses the latest research advances on design and manufacture of novel fiber-reinforced scaffolds for soft tissue repair and how fiber addition affects their structural characteristics, mechanical strength and biological activities in vitro and in vivo. In general, the concept of fiber-reinforced scaffolds with adjustable microstructures, mechanical properties and degradation rates can provide an effective platform and promising method for developing satisfactory biomechanically functional implantations for soft tissue engineering or regenerative medicine.

Negative Outcomes of Poly(l-Lactic Acid) Fiber-Reinforced Scaffolds in an Ovine Total Meniscus Replacement Model.

Our objective was to test the efficacy of collagen-hyaluronan scaffolds reinforced with poly(l-lactic acid) (PLLA) fibers in an ovine total meniscus replacement model. Scaffolds were implanted into 9 sheep (n = 1 at 8 weeks, n = 2 at 16 weeks, n = 3 at both 24, 32 weeks) following total medial meniscectomy. From 16 weeks on, explants were characterized by confined compression creep, histological, and biochemical analyses. Articular surfaces were observed macroscopically and damage was ranked histologically using the Mankin score. At sacrifice, three of the nine PLLA scaffolds had completely ruptured, and the intact scaffolds experienced progressive shape changes and severe narrowing in the body region at 16, 24, and 32 weeks. Aggregate compressive modulus and permeability did not improve with time. Histological and biochemical analyses showed significantly less extracellular matrix and less matrix organization compared to native tissue. Osteophytes, bone erosion, and cartilage damage were observed, increasing with time postimplantation. A buildup of lactic acid and/or the rapid loss of scaffold mechanical integrity due to PLLA degradation are probable causes for the joint abnormalities observed in this study. These results are in sharp contrast to those of our previous successful total meniscus replacement studies using polyarylate [p(DTD DD)] fiber-reinforced scaffolds. This suggests that PLLA fiber as produced in this study cannot be used as reinforcement for a meniscus replacement scaffold.

One-Year Outcomes of Total Meniscus Reconstruction Using a Novel Fiber-Reinforced Scaffold in an Ovine Model

Background: Meniscus injuries and resulting meniscectomies lead to joint deterioration, causing pain, discomfort, and instability. Tissue-engineered devices to replace the meniscus have not shown consistent success with regard to function, mechanical integrity, or protection of cartilage. Purpose: To evaluate a novel resorbable polymer fiber–reinforced meniscus reconstruction scaffold in an ovine model for 52 weeks and assess its integrity, tensile and compressive mechanics, cell phenotypes, matrix organization and content, and protection of the articular cartilage surfaces. Study Design: Controlled laboratory study. Methods: Eight skeletally mature ewes were implanted with the fiber-reinforced scaffold after total meniscectomy, and 2 additional animals had untreated total meniscectomies. Animals were sacrificed at 52 weeks, and the explants and articular surfaces were analyzed macroscopically. Explants were characterized by ultimate tensile testing, confined compression creep testing, and biochemical, histological, and immunohistochemical analyses. Cartilage damage was characterized using the Mankin score on histologic slides from both the femur and tibia. Results: One sheep was removed from the study because of a torn extensor tendon; the remaining 7 explants remained fully intact and incorporated into the bone tunnels. All explants exhibited functional tensile loads, tensile stiffnesses, and compressive moduli. Fibrocartilagenous repair with both types 1 and 2 collagen were observed, with areas of matrix organization and biochemical content similar to native tissue. Narrowing in the body region was observed in 5 of 7 explants. Mankin scores showed less cartilage damage in the explant group (femoral condyle: 3.43 ± 0.79, tibial plateau: 3.50 ± 1.63) than in the meniscectomy group (femoral condyle: 8.50 ± 3.54, tibial plateau: 6.75 ± 2.47) and were comparable with Mankin scores at the previously reported 16- and 32-week time points. Conclusion: A resorbable fiber-reinforced meniscus scaffold supports formation of functional neomeniscus tissue, with the potential to prevent joint degeneration that typically occurs after total meniscectomy. Further studies with improvements to the initial mechanics of the scaffold and testing for longer time periods are warranted. Clinical Relevance: Meniscectomy is an extremely common orthopaedic procedure, and few options currently exist for the treatment of significant loss of meniscus tissue. Successful development of a tissue-engineered meniscus scaffold could substantially reduce the incidence of postmeniscectomy joint degeneration and the subsequent procedures used for its treatment.

Vascularized Bone Tissue Formation Induced by Fiber-Reinforced Scaffolds Cultured with Osteoblasts and Endothelial Cells

The repair of the damaged bone tissue caused by damage or bone disease was still a problem. Current strategies including the use of autografts and allografts have the disadvantages, namely, diseases transmission, tissue availability and donor morbidity. Bone tissue engineering has been developed and regarded as a new way of regenerating bone tissues to repair or substitute damaged or diseased ones. The main limitation in engineering in vitro tissues is the lack of a sufficient blood vessel system, the vascularization. In this paper, a new-typed hydroxyapatite/collagen composite scaffold which was reinforced by chitosan fibers and cultured with osteoblasts and endothelial cells was fabricated. General observation, histological observation, detection of the degree of vascularization, and X-ray examination had been done to learn the effect of vascularized bone repair materials on the regeneration of bone. The results show that new vessel and bone formed using implant cultured with osteoblasts and endothelial cells. Nanofiber-reinforced scaffold cultured with osteoblasts and endothelial cells can induce vascularized bone tissue formation.

The Use of Fiber-Reinforced Scaffolds Cocultured with Schwann Cells and Vascular Endothelial Cells to Repair Rabbit Sciatic Nerve Defect with Vascularization

To explore the feasibility of biodegradable fiber-reinforced 3D scaffolds with satisfactory mechanical properties for the repair of long-distance sciatic nerve defect in rabbits and effects of vascularized graft in early stage on the recovery of neurological function, Schwann cells and vascular endothelial cells were cocultured in the fiber-reinforced 3D scaffolds. Experiment group which used prevascularized nerve complex for the repair of sciatic nerve defect and control group which only cultured with Schwann cells were set. The animals in both groups underwent electromyography to show the status of the neurological function recovery at 4, 8, and 16 weeks after the surgery. Sciatic nerve regeneration and myelination were observed under the light microscope and electron microscope. Myelin sheath thickness, axonal diameter, and number of myelinated nerve fiber were quantitatively analyzed using image analysis system. The recovery of foot ulcer, the velocity of nerve conduction, the number of regenerating nerve fiber, and the recovery of ultrastructure were increased in the experimental group than those in the control group. Prevascularized tissue engineered fiber-reinforced 3D scaffolds for the repair of sciatic nerve defects in rabbits can effectively promote the recovery of neurological function.

Design and mechanical evaluation of a novel fiber‐reinforced scaffold for meniscus replacement

A fiber-reinforced degradable scaffold for replacement of meniscal tissue was designed, fabricated, and mechanically evaluated. The hypotheses were that (1) the fiber network design would share a portion of compressive loads via the generation of circumferential tensile loads, and (2) the scaffold tensile properties would be similar to those of the meniscus. Two meniscus scaffold designs varying in fiber content (1000 or 500 fibers: MS1000, MS500) underwent cyclic compressive loading up to 100 and 250N, with resultant tensile loads measured at the anterior and posterior anchors. Standard tensile testing was also performed on each device and ovine menisci. Both scaffolds generated tensile loads directly proportional to the applied compressive loads, with MS1000 scaffolds generating approximately twice the tensile loads of MS500 scaffolds. The tensile strength of MS1000 scaffolds was significantly higher than that of the medial and lateral ovine menisci, and approximately twice that of the MS500 scaffolds. The stiffness of MS1000 scaffolds was lower than that of the lateral meniscus, but not statistically different from that of the medial meniscus. These results support our hypotheses that this novel fiber-reinforced scaffold can mimic the tensile and hoop stress behavior of normal meniscal tissue under compressive loading. The circumferential tensile strength and stiffness are appropriate for a meniscus replacement device.

Improving the mechanical properties of chitosan-based heart valve scaffolds using chitosan fibers

Chitosan is being widely studied for tissue engineering applications due to its biocompatibility and biodegradability. However, its use in load-bearing applications is limited due to low mechanical properties. In this study, we investigated the effectiveness of a chitosan fiber reinforcement approach to enhancing the mechanical properties of chitosan scaffolds. Chitosan fibers were fabricated using a solution extrusion and neutralization method and incorporated into porous chitosan scaffolds. The effects of fiber/scaffold mass ratio, fiber mechanical properties and fiber length on scaffold mechanical properties were studied. The results showed that incorporating fibers improved scaffold strength and stiffness in proportion to the fiber/scaffold mass ratio. A fiber-reinforced, heart valve scaffold achieved leaflet tensile strength values of 220±17 kPa, comparable to the radial values of human pulmonary valve leaflets. Additionally, the effects of 2 mm fibers were found to be up to threefold greater than 10 mm fibers at identical mass ratios. Heparin crosslinking of fibers produced a reduction in fiber strength, and thus failed to produce additional improvements to fiber-reinforced scaffold properties. Despite this reduction in fiber strength, heparin-modified fibers still improved the mechanical properties of reinforced scaffolds, but to a lesser extent than unmodified fibers. The results demonstrate that chitosan fiber reinforcement can be used to achieve porous chitosan scaffold strength approaching that of tissue, and that fiber length and mechanical properties are important parameters in defining the degree of mechanical improvement.

Fiber-reinforced scaffolds for tissue engineering and regenerative medicine: use of traditional textile substrates to nanofibrous arrays

Regenerative medicine is a promising therapeutic strategy for the repair and replacement of diseased or injured tissues and organs. The main approach for this method is the fabrication and use of scaffold materials to act as a surrogate framework and promote cell-seeded populations to develop into a mature and functional tissue. Scaffold based strategies for regenerative medicine have focused on the use of three dimensional, biocompatible, biodegradable structures to provide an adequate template for ex vivo cell expansion and maturation, native tissue ingrowth, and restoration of the original tissue qualities with respect to the tissue's biochemical constituents, morphology, form, and function. To achieve this, the use of fiber and/or textile substrates have been used as either the underlying skeleton or reinforcing agents with or without three-dimensional matrices to provide scaffolds that exhibit suitable mechanical properties, high cellularity, and better mimicry of the natural tissue organization and its resulting composition. In this article we discuss (1) fiber reinforcement in natural tissues, (2) literature examples of fiber reinforcement in engineered tissues, and (3) strategies and next steps to expand this field. Fiber reinforcement continues to be an ideal strategy for tissue scaffolds that require mechanical reinforcement while providing high surface volume in a compliant form.

Porous, resorbable, fiber-reinforced scaffolds tailored for articular cartilage repair.

Porous 75:25 poly(D,L-lactide-co-glycolide) scaffolds reinforced with polyglycolide fibers were prepared with mechanical properties tailored for use in articular cartilage repair. Compression testing was performed to investigate the influence of physiological testing conditions, manufacturing method, anisotropic properties due to predominant fiber orientation, amounts of fiber reinforcement (0 to 20 wt, %), and viscoelasticity via a range of strain rates. Using the same testing modality, the mechanical properties of the scaffolds were compared with pig and goat articular cartilage. Results showed that mechanical properties of the scaffolds under physiological conditions (aqueous, 37 degrees C) were much lower than when tested under ambient conditions. The manufacturing method and anisotropy of the scaffolds significantly influenced the mechanical properties. The compressive modulus and yield strength proportionally increased with increasing fiber reinforcement up to 20%. From 0.01 to 10 mm/mm/min strain rate, the compressive modulus increased in a logarithmic fashion, and the yield strength increased in a semi-log fashion. The compressive modulus of the non-reinforced scaffolds was most similar to the pig and goat articular cartilage when compared using similar testing conditions and modality, but the improvement in yield strength using the stiffer scaffolds with fiber reinforcement could provide needed structural support for in vivo loads.