Melt electrospun fibers of poly(ϵ-caprolactone) are accurately deposited using an automated stage as the collector. Matching the translation speed of the collector to the speed of the melt electrospinning jet establishes control over the location of fiber deposition. In this sense, melt electrospinning writing can be seen to bridge the gap between solution electrospinning and direct writing additive manufacturing processes.

Direct writing by way of melt electrospinning

Articular hyaline cartilage is extensively hydrated, but it is neither innervated nor vascularized, and its low cell density allows only extremely limited self-renewal. Most clinical and research efforts currently focus on the restoration of cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss current clinical approaches for repairing cartilage, as well as research approaches which are currently developing, and those under translation into clinical practice. We also describe potential future directions in this area, including tissue engineering based on scaffolding and/or stem cells as well as a combination of gene and cell therapy. Particular focus is placed on cell-based approaches and the potential of recently characterized chondro-progenitors; progress with induced pluripotent stem cells is also discussed. In this context, we also consider the ability of different types of stem cell to restore hyaline cartilage and the importance of mimicking the environment in vivo during cell expansion and differentiation into mature chondrocytes.

https://www.mdpi.com/1422-0067/19/8/2366/pdf

Repair of Damaged Articular Cartilage: Current Approaches and Future Directions.

Decellularized extracellular matrix scaffolds: Recent trends and emerging strategies in tissue engineering

Biodegradable Polymers for Biomedical Additive Manufacturing

Articular cartilage is composed of chondrons within a territorial matrix surrounded by a highly organized extracellular matrix comprising collagen II fibrils, proteoglycans, glycosaminoglycans, and non-collagenous proteins. Damaged articular cartilage has a limited potential for healing and untreated defects often progress to osteoarthritis. High hopes have been pinned on regenerative medicine strategies to meet the challenge of preventing progress to late osteoarthritis. One such strategy, autologous chondrocyte implantation (ACI), was first reported in 1994 as a treatment for deep focal articular cartilage defects. ACI has since evolved to become a worldwide well-established surgical technique. For ACI, chondrocytes are harvested from the lesser weight bearing edge of the joint by arthroscopy, their numbers expanded in monolayer culture for at least four weeks, and then re-implanted in the damaged region under a natural or synthetic membrane via an open joint procedure. We consider the evolution of ACI to become an established cell therapy, its current limitations, and on-going strategies to improve its efficacy. The most promising developments involving cells and natural or synthetic biomaterials will be highlighted.

https://www.mdpi.com/2306-5354/6/1/22/pdf

Regenerative Medicine: A Review of the Evolution of Autologous Chondrocyte Implantation (ACI) Therapy.

Emerging 3D printing technology permits innovative approaches to manufacture cartilage scaffolds associated with layer-by-layer mechanical property adaptation. However, information about gradients of mechanical properties in human articular cartilage is limited. In this study, we quantified a zone-dependent change of local elastic modulus of human femoral condyle cartilage by using an instrumented indentation technique. From the cartilage superficial zone towards the calcified layer, a gradient of elastic modulus values between 0.020 ± 0.003 MPa and 6.44 ± 1.02 MPa was measured. To validate the tissue quality, the histological tissue composition was visualized by glycosaminoglycan and collagen staining. This work aims to introduce a new protocol to investigate the zone-dependent mechanical properties of graded structures, such as human articular cartilage. From this knowledge, better cartilage repair strategies could be tailored in the future.

/pdf/zone-dependent-mechanical-properties-of-human-articular-23h17hk410.pdf

Zone-dependent mechanical properties of human articular cartilage obtained by indentation measurements.

Cellular thermoplastic structures with multiscale porosity (1–300 µm microporosity to 0.3–10 mm macroporosity) are produced from an integrated approach of 3D printing by Fused Deposition Modeling printing and Supercritical CO2 Foaming. Porous strands and related hierarchical structures are processed in one continuous step. Influence of printing parameters (e.g., deposition temperature and speed) on foam porosity and pores distribution is described for a semicrystalline food grade Poly-Lactide Acid. The process is then applied to other thermoplastics filament with different mechanical properties. In particular, a composite blend of Poly-l-Lactide and βTCP (90–10) ceramic particles and a soft copolymer Poly-Lactide-co-Caprolactone are processed to print foamed strands with various internal cellular microstructures. The dynamic material transformation phenomena controlling the microstructure upon deposition and foaming are determined. This new additive manufacturing method introduces for the first time the possibility to tune cellular morphology in situ and on line, offering an unmatched freedom to design anisotropy in 3D.

3D Printing of Polymers with Hierarchical Continuous Porosity

Tissue decellularisation has gained much attention in regenerative medicine as an alternative to synthetic materials. In decellularised tissues, biological cues can be maintained and provide cellular environments still unmet by synthetic materials. Supercritical CO2 (scCO2 ) has recently emerged as a promising alternative decellularisation technique to aggressive detergents; in addition, scCO2 provides innate sterilisation. However, to date, decellularisation with scCO2 is limited to only a few tissue types with low cellular density. In the current study, a scCO2 technique to decellularise high density tissues, including articular cartilage, tendon and skin, was developed. Results showed that most of the cellular material was removed, while the sample structure and biocompatibility was preserved. The DNA content was reduced in cartilage, tendon and skin as compared to the native tissue. The treatment did not affect the initial tendon elastic modulus [reduced from 126.35 ± 9.79 MPa to 113.48 ± 8.48 MPa (p 〉 0.05)], while it reduced the cartilage one [from 12.06 ± 2.14 MPa to 1.17 ± 0.34 MPa (p 〈 0.0001)]. Interestingly, cell adhesion molecules such as fibronectin and laminin were still present in the tissues after decellularisation. Bovine chondrocytes were metabolically active and adhered to the surface of all decellularised tissues after 1 week of cell culture. The developed method has the potential to become a cost-effective, one-step procedure for the decellularisation of dense tissues.

/pdf/decellularised-tissues-obtained-by-a-co2-philic-detergent-1styksodsx.pdf

Decellularised tissues obtained by a CO2-philic detergent and supercritical CO2.

Chronic and acute tendon injuries are frequent afflictions, for which treatment is often long and unsatisfactory. When facing extended injuries, matrices and scaffolds with sufficient biomechanical properties are required for surgical repair and could additionally serve as supports for cellular therapies to improve healing. In this study, protocols of either commonly used detergents only (SDS 1%, Triton 1%, TBP 1%, and Tween-20 1%) or a combination of freeze/thaw (F/T) cycles with decellularization agents (NaCl 1M, ddH2 O) were evaluated for the decellularization of horse equine superficial digital flexor tendon (SDFT) for hand flexor or extensor tendon reconstruction. Decellularization efficiency was assessed microscopically by histological staining (HE, DAPI) and DNA quantification. Macroscopical structure and biomechanical integrity of the tendon matrices were further assessed by gross observation, histological staining (SR), and mechanical testing (ultimate strain and stress, Young's modulus, energy to failure) for select protocols. Decellularization with hypertonic NaCl 1M in association with F/T cycles produced the most robust tendon matrices, which were nontoxic after 10 days for subsequent recellularization with human fetal progenitor tendon cells (hFPTs). This standardized protocol uses a less aggressive decellularization agent than current practice, which allows subsequent reseeding with allogenic cells, therefore making them very suitable and bioengineered tendon matrices for human tendon reconstruction in the clinic.

Jens Antons

Papers

Zone-dependent mechanical properties of human articular cartilage obtained by indentation measurements.

3D Printing of Polymers with Hierarchical Continuous Porosity

Decellularised tissues obtained by a CO2-philic detergent and supercritical CO2.

Efficient decellularization of equine tendon with preserved biomechanical properties and cytocompatibility for human tendon surgery indications.