3D-Printed Poly(ε-caprolactone) Scaffold Augmented With Mesenchymal Stem Cells for Total Meniscal Substitution: A 12- and 24-Week Animal Study in a Rabbit Model.

BACKGROUND: Total meniscectomy leads to knee osteoarthritis in the long term. The poly(ε-caprolactone) (PCL) scaffold is a promising material for meniscal tissue regeneration, but cell-free scaffolds result in relatively poor tissue regeneration and lead to joint degeneration. HYPOTHESIS: A novel, 3-dimensional (3D)-printed PCL scaffold augmented with mesenchymal stem cells (MSCs) would offer benefits in meniscal regeneration and cartilage protection. STUDY DESIGN: Controlled laboratory study. METHODS: PCL meniscal scaffolds were 3D printed and seeded with bone marrow-derived MSCs. Seventy-two New Zealand White rabbits were included and were divided into 4 groups: cell-seeded scaffold, cell-free scaffold, sham operation, and total meniscectomy alone. The regeneration of the implanted tissue and the degeneration of articular cartilage were assessed by gross and microscopic (histological and scanning electron microscope) analysis at 12 and 24 weeks postoperatively. The mechanical properties of implants were also evaluated (tensile and compressive testing). RESULTS: Compared with the cell-free group, the cell-seeded scaffold showed notably better gross appearance, with a shiny white color and a smooth surface. Fibrochondrocytes with extracellular collagen type I, II, and III and proteoglycans were found in both seeded and cell-free scaffold implants at 12 and 24 weeks, while the results were significantly better for the cell-seeded group at week 24. Furthermore, the cell-seeded group presented notably lower cartilage degeneration in both femur and tibia compared with the cell-free or meniscectomy group. Both the tensile and compressive properties of the implants in the cell-seeded group were significantly increased compared with those of the cell-free group. CONCLUSION: Seeding MSCs in the PCL scaffold increased its fibrocartilaginous tissue regeneration and mechanical strength, providing a functional replacement to protect articular cartilage from damage after total meniscectomy. CLINICAL RELEVANCE: The study suggests the potential of the novel 3D PCL scaffold augmented with MSCs as an alternative meniscal substitution, although this approach requires further improvement before being used in clinical practice.

Role of scaffold mean pore size in meniscus regeneration.

UNLABELLED: Recently, meniscus tissue engineering offers a promising management for meniscus regeneration. Although rarely reported, the microarchitectures of scaffolds can deeply influence the behaviors of endogenous or exogenous stem/progenitor cells and subsequent tissue formation in meniscus tissue engineering. Herein, a series of three-dimensional (3D) poly(ε-caprolactone) (PCL) scaffolds with three distinct mean pore sizes (i.e., 215, 320, and 515µm) were fabricated via fused deposition modeling. The scaffold with the mean pore size of 215µm significantly improved both the proliferation and extracellular matrix (ECM) production/deposition of mesenchymal stem cells compared to all other groups in vitro. Moreover, scaffolds with mean pore size of 215µm exhibited the greatest tensile and compressive moduli in all the acellular and cellular studies. In addition, the relatively better results of fibrocartilaginous tissue formation and chondroprotection were observed in the 215µm scaffold group after substituting the rabbit medial meniscectomy for 12weeks. Overall, the mean pore size of 3D-printed PCL scaffold could affect cell behavior, ECM production, biomechanics, and repair effect significantly. The PCL scaffold with mean pore size of 215µm presented superior results both in vitro and in vivo, which could be an alternative for meniscus tissue engineering. STATEMENT OF SIGNIFICANCE: Meniscus tissue engineering provides a promising strategy for meniscus regeneration. In this regard, the microarchitectures (e.g., mean pore size) of scaffolds remarkably impact the behaviors of cells and subsequent tissue formation, which has been rarely reported. Herein, three three-dimensional poly(ε-caprolactone) scaffolds with different mean pore sizes (i.e., 215, 320, and 515µm) were fabricated via fused deposition modeling. The results suggested that the mean pore size significantly affected the behaviors of endogenous or exogenous stem/progenitor cells and subsequent tissue formation. This study furthers our understanding of the cell-scaffold interaction in meniscus tissue engineering, which provides unique insight into the design of meniscus scaffolds for future clinical application.

Thermogel-Coated Poly(ε-Caprolactone) Composite Scaffold for Enhanced Cartilage Tissue Engineering.

A three-dimensional (3D) composite scaffold was prepared for enhanced cartilage tissue engineering, which was composed of a poly(ε-caprolactone) (PCL) backbone network and a poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA⁻PEG⁻PLGA) thermogel surface. The composite scaffold not only possessed adequate mechanical strength similar to native osteochondral tissue as a benefit of the PCL backbone, but also maintained cell-friendly microenvironment of the hydrogel. The PCL network with homogeneously-controlled pore size and total pore interconnectivity was fabricated by fused deposition modeling (FDM), and was impregnated into the PLGA⁻PEG⁻PLGA solution at low temperature (e.g., 4 °C). The PCL/Gel composite scaffold was obtained after gelation induced by incubation at body temperature (i.e., 37 °C). The composite scaffold showed a greater number of cell retention and proliferation in comparison to the PCL platform. In addition, the composite scaffold promoted the encapsulated mesenchymal stromal cells (MSCs) to differentiate chondrogenically with a greater amount of cartilage-specific matrix production compared to the PCL scaffold or thermogel. Therefore, the 3D PCL/Gel composite scaffold may exhibit great potential for in vivo cartilage regeneration.

High-Pressure Compression-Molded Porous Resorbable Polymer/Hydroxyapatite Composite Scaffold for Cranial Bone Regeneration.

Fabricating porous scaffolds with sufficient mechanical properties is a challenge for healing bone defects. High-pressure compression-molded (HPCM) porous composite scaffold comprising poly(l-lactide) (PLLA), poly(lactide-co-glycolide) (PLGA), and hydroxyapatite (HA) was prepared and showed upregulated mechanical properties due to a solid network structure and a highly ordered crystalline architecture. The compressive yield strength and modulus of the HPCM scaffold molded at 1000 MPa and 180 °C were 0.91 and 6.84 MPa, respectively. The HPCM scaffold also exhibited an interconnected porous architecture with porosity greater than 80%, an appropriate degradation rate, and enhanced cell proliferation. Moreover, the HPCM scaffold supported the healing of a rat calvarial defect in vivo.

In vitro evaluation of anticancer nanomedicines based on doxorubicin and amphiphilic Y-shaped copolymers.

Four monomethoxy poly(ethylene glycol)-poly(L-lactide-co-glycolide)(2) (mPEG-P( LA-co-GA)(2)) copolymers were synthesized by ring-opening polymerization of L-lactide and glycolide with double hydroxyl functionalized mPEG (mPEG-(OH)(2)) as macroinitiator and stannous octoate as catalyst. The copolymers self-assembled into nanoscale micellar/vesicular aggregations in phosphate buffer at pH 7.4. Doxorubicin (DOX), an anthracycline anticancer drug, was loaded into the micellar/vesicular nanoparticles, yielding micellar/vesicular nanomedicines. The in vitro release behaviors could be adjusted by content of hydrophobic polyester and pH of the release medium. In vitro cell experiments showed that the intracellular DOX release could be adjusted by content of P(LA-co-GA), and the nanomedicines displayed effective proliferation inhibition against Henrietta Lacks's cells with different culture times. Hemolysis tests indicated that the copolymers were hemocompatible, and the presence of copolymers could reduce the hemolysis ratio of DOX significantly. These results suggested that the novel anticancer nanomedicines based on DOX and amphiphilic Y-shaped copolymers were attractive candidates as tumor tissular and intracellular targeting drug delivery systems in vivo, with enhanced stability during circulation and accelerated drug release at the target sites.