A comprehensive bench-to-bed look into the application of gamma-sterilized 3D-printed polycaprolactone/hydroxyapatite implants for craniomaxillofacial defects, an in vitro, in vivo, and clinical study.

This study investigates the safety and efficacy of 3D-printed polycaprolactone/hydroxyapatite (PCL/HA) scaffolds for patient-specific cranioplasty surgeries, employing liquid deposition modeling (LDM) technology. This research is pioneering as it explores the impact of gamma radiation on PCL/HA scaffolds and utilizes printing ink with the highest content of HA known in the composite. The mechanical, morphological, and macromolecular stability of the gamma-sterilized scaffolds were verified before implantation. Subsequent research involving animal subjects was conducted to explore the effects of sterilized implants. Eventually, three clinical cases were selected for the implantation studies as part of a phase 1 non-randomized open-label clinical trial. It was shown that a 25 kGy gamma-ray dose for sterilizing the printed implants did not alter the required geometrical precision of the printed implants. The implants exhibited well-distributed HA and strength comparable to cancellous bone. Gamma radiation reduced hydrophobicity and water uptake capacity without inducing pyrogenic or inflammatory responses. Personalized PCL/HA substitutes successfully treated various craniomaxillofacial defects, including trauma-induced facial asymmetry and congenital deformities. HA nanoparticles in the ink stimulated significant osteoconductive responses within three months of implantation. Moreover, the results revealed that while larger implants may exhibit a slower bone formation response in comparison to smaller implants, they generally had an acceptable rate and volume of bone formation. This clinical trial suggests the application of a sterilized PCL/HA composite for craniomaxillofacial surgery is safe and could be considered as a substitute for autologous bone.

Effects of low-intensity pulsed ultrasound stimulation on cell seeded 3D hybrid scaffold as a novel strategy for meniscus regeneration: An in vitro study.

Menisci are fibrocartilaginous structures in the knee joint with an inadequate regenerative capacity, which causes low healing potential and further leads to osteoarthritis. Recently, three-dimensional (3D) printing techniques and ultrasound treatment have gained plenty of attention for meniscus tissue engineering. The present study investigates the effectiveness of low-intensity pulsed ultrasound stimulations (LIPUS) on the proliferation, viability, morphology, and gene expression of the chondrocytes seeded on 3D printed polyurethane scaffolds dip-coated with gellan gum, hyaluronic acid, and glucosamine. LIPUS stimulation was performed at 100, 200, and 300 mW/cm2 intensities for 20 min/day. A faster gap closure (78.08 ± 2.56%) in the migration scratch assay was observed in the 200 mW/cm2 group after 24 h. Also, inverted microscopic and scanning electron microscopic images showed no cell morphology changes during LIPUS exposure at different intensities. The 3D cultured chondrocytes under LIPUS treatment revealed a promotion in cell proliferation rate and viability as the intensity doses increased. Additionally, LIPUS could stimulate chondrocytes to overexpress the aggrecan and collagen II genes and improve their chondrogenic phenotype. This study recommends that the combination of LIPUS treatment and 3D hybrid scaffolds can be considered as a valuable treatment for meniscus regeneration based on our in vitro data.

Fabrication and assessment of a novel hybrid scaffold consisted of polyurethane-gellan gum-hyaluronic acid-glucosamine for meniscus tissue engineering.

The meniscus has inadequate intrinsic regenerative capacity and its damage can lead to degeneration of articular cartilage. Meniscus tissue engineering aims to restore an injured meniscus followed by returning its normal function through bioengineered scaffolds. In the present study, the structural and biological properties of 3D-printed polyurethane (PU) scaffolds dip-coated with gellan gum (GG), hyaluronic acid (HA), and glucosamine (GA) were investigated. The optimum concentration of GG was 3% (w/v) with maintaining porosity at 88.1%. The surface coating of GG-HA-GA onto the PU scaffolds increased the compression modulus from 30.30 kPa to 59.10 kPa, the water uptake ratio from 27.33% to 60.80%, degradation rate from 5.18% to 8.84%, whereas the contact angle was reduced from 104.8° to 59.3°. MTT assay, acridine orange/ethidium bromide (AO/EB) fluorescent staining, and SEM were adopted to assess the behavior of the seeded chondrocytes on scaffolds, and it was found that the ternary surface coating stimulated the cell proliferation, viability, and adhesion. Moreover, the coated scaffolds showed higher expression levels of collagen II and aggrecan genes at day 7 compared to the control groups. Therefore, the fabricated PU-3% (w/v) GG-HA-GA scaffold can be considered as a promising scaffold for meniscus tissue engineering.

Poly (sodium 4-styrene sulfonate)-modified hydroxyapatite nanoparticles in zein-based scaffold as a drug carrier for vancomycin.

In order to prepare bone tissue engineered scaffolds, zein, a natural polymer isolated from corn, was used as a starting material. Zein provides ideal properties for tissue engineered scaffolds, and the products derived from its degradation are non-toxic. To enhance the osteogenic properties of the scaffold, hydroxyapatite mineral was used in the form of nanospheres. Hydroxyapatite nanoparticles are designed to carry a drug in addition to the role they play in bone tissue engineering. The surface of the hydroxyapatite nanoparticles was modified with negatively charged poly (sodium 4-styrene sulfonate) polymer, and their surface was then loaded with positively charged Vancomycin as a model drug. The scaffolds were evaluated by structural and cellular assays. FTIR and particle zeta potential tests confirmed the presence of PSS and Vancomycin in nanoparticles. The results showed a decrease in the porosity of the scaffolds and a reduction of scaffold degradation over an eight week period by increasing the concentration of hydroxyapatite nanoparticles, compared to the pure zein sample. It was observed that increasing the concentration of nanoparticles to an optimum concentration can improve the mechanical properties of scaffolds. The drug release from the scaffolds over two weeks was increased with an increase in hydroxyapatite concentration, and cell viability assays showed >90% viability of cells in scaffolds containing hydroxyapatite nanoparticles, which were confirmed to be accumulating in a proper fashion according to cell adhesion assays.