Biodegradable Multi-layered Silk Fibroin-PCL Stent for the Management of Cervical Atresia: In Vitro Cytocompatibility and Extracellular Matrix Remodeling In Vivo.

Cervical atresia is a rare congenital Müllerian duct anomaly that manifests as the absence or deformed nonfunctional presence of the cervix. Herein, a multi-layered biodegradable stent is fabricated using a homogeneous blend of silk fibroin with polycaprolactone using hexafluoroisopropanol as a common solution. Briefly, a concentric cylinder of 3D honeycomb layer is sandwiched within electrospun sheets for fixing at the cervico-uterine junction to pave the way of cervical reconstruction. An average length of 40 mm with 3 mm diameter is fabricated for the hybrid stent design. SEM evidences an evenly distributed pore architecture of the electrospun layer, and mechanical characterization of stent reveals a tensile strength of 1.7 ± 0.2 MPa, with a Young's modulus of 5.9 ± 0.1 MPa. Physico-chemical characterization confirms the presence of silk fibroin and poly caprolactone within the engineered stent. Following 14 days of pepsin enzymatic degradation, 18% degradation and a contact angle measurement of 97° are observed. In vitro cytocompatibility studies are performed using site-specific primary human cervical squamous, columnar epithelial cells, and human endometrial stromal cells. The study demonstrates non-cytotoxic cells' viability (no significant toxicity), improved cell anchoring, adherence among the stent layers, and proliferation in the 3D microenvironment. Furthermore, in vivo subcutaneous studies in the rodent model indicate that the implanted stent undergoes constructive remodeling, neo-tissue creation, neo-vasculature formation, and re-epithelialization while maintaining patency for 2 months.

Design modification of surgical drill bit for final osteotomy site preparation towards improved bone-implant contact.

Implant stability significantly impacts accelerated osseointegration, leading to faster patient recovery. Both primary and secondary stability necessitates superior bone-implant contact influenced by the surgical tool required to prepare the final osteotomy site. Besides, excessive shearing and frictional forces generate heat causing local tissue necrosis. Hence, surgical procedure necessitates proper irrigation with water to minimize heat generation. Notably, the water irrigation system removes bone chips and osseous coagulums, which may help accelerate osseointegration and improve bone-implant contact. The inferior bone-implant contact and thermal necrosis at the osteotomy site are primarily responsible for poor osseointegration and eventual failure. Therefore, optimizing tool geometry is key to minimizing shear force, heat generation, and necrosis during final osteotomy site preparation. The present study explores modified drilling tool geometry, especially cutting edge for osteotomy site preparation. The mathematical modeling is used to find out ideal cutting-edge geometry that facilitates drilling under relatively less operational force (0.55-5.24 N) and torque (98.8-154.5 N-mm) with a significant reduction (28.78%-30.87%) in heat generation. Twenty-three conceivable designs were obtained using the mathematical model; however, only three have shown promising results in static structural FEM platforms. These drill bits are designed for the final drilling operation and need to be carried out during the final osteotomy site preparation.

Comparative evaluation of a patient-specific customised plate designs and screws for partial mandibular reconstruction.

Mandibles with odontogenic tumors are often partially reconstructed with a metallic bone graft analogue with dental roots, crowns, along with a customized plate fixed with monocortical or bicortical screws, following resection of the tumor. In this study, two different designs of patient specific customized Ti reconstruction plates, solid and plate with holes, were considered. Fixation through both bicortical and monocortical screw types were investigated. FE models of the reconstructed mandibles were developed to analyse the influence of the plate-screw type combination on the load transfer across the mandibles under a mastication cycle. The effective homogenized orthotropic material properties of the lattice structures with 0.6 mm fibre diameter with 0.5 mm inter-fibre space were assigned to material properties for the bone graft analogue. The study shows that the combination of plate and screw types influences the state of stresses in the reconstructed mandible. Based on the results of this patient specific study, following resection of the tumor, either solid Ti plate with bicortical screws or Ti plate with holes along with monocortical screws may be used for partial mandibulectomy. It should also be noted that stresses in none of the plates or screws exceeded the yield limit for Ti under the mastication cycle indicating that the components are safe for mandibular reconstruction. However, the choice of this combination of reconstruction plates and screws is dependant on the condition and severity of the tumor in the diseased mandible.

High fibroin-loaded silk-PCL electrospun fiber with core-shell morphology promotes epithelialization with accelerated wound healing.

Silk fibroin (SF) is a widely explored biopolymer for wound-healing applications due to the presence of amino acids in the biodegradable polymer chain with superior mechanical properties. Herein, a high SF-loaded fibrous matrix along with poly(ε-caprolactone) (PCL) was fabricated using electrospinning of emulsion and blend compositions to modulate nanostructure morphology. A comparative study of the physicomechanical properties of electrospun fibers with emulsion (eS7P3) and homogenous blend (bS7P3) was performed as well. In both compositions, SF loading of up to 70% was successfully achieved in the spun fibers while emulsion yielded core-shell morphology, and the blend resulted in monolith fiber architecture as evidenced by TEM microscopy. Further characterization revealed superior mechanical properties in S7P3 fiber with core-shell morphology, as compared to those in the monolith in terms of a higher degree of crystallinity with Young's modulus of 60 MPa under tensile test and nanoindentation modulus of 1.59 ± 0.8 GPa. Further, eS7P3 nanostructure morphology containing silk in the core with a thin outer layer of PCL facilitated relatively faster biodegradation in the lysozyme medium, as compared to that in the monolith. Owing to the presence of a hydrophobic shell, protein adsorption on the fibrous mat presented slow but steady kinetics up to 24 h. When the scaffold was seeded with human placenta-derived mesenchymal stem cells (hPMSCs), in vitro study confirmed that the eS7P3 structure had marginally higher cell proliferation with superior cell infiltration than the monolith. Further, in vivo study involving a rodent model showed the potential of the eS7P3 fiber substrate with a core-shell structure for accelerating full-thickness wound healing by inducing hair follicle and wound closure with less scar formation after 15 days.

Load transfer across a mandible during a mastication cycle: The effects of odontogenic tumour.

The extent to which load transfer in a diseased mandible with odontogenic tumour might influence the potential risk of pathological fracture has scarcely been investigated. The study sought to investigate the quantitative deviations in load transfer across healthy and cancer-affected (diseased) mandibles having odontogenic tumours. The effect of size of the tumours (small: 9 mm diameter, large: 19 mm diameter), and variation in bone mechanical (elastic) properties of the mandible on load transfer in cancer-affected mandibles during a mastication cycle have been investigated. Based on patient-specific computed tomography-scan datasets, detailed three-dimensional finite element models of healthy and diseased mandibles were developed. High stresses of 25-30 MPa and strains ∼700 µÎµ were observed in the healthy mandible during the right molar bite. However, marginal deviations were observed in principal stress distributions in the diseased mandibles with small- and large-sized tumours, as compared to the healthy mandible. Maximum principal strains of ∼1474 µÎµ were found in the body region adjacent to the symphysis region for small-sized tumour. Whereas for large-sized tumour, maximum strains of ∼2700 µÎµ were observed in the right buccal regions. Reduction in Young's modulus due to different stages of odontogenic tumours had a localised effect on the principal stress distributions, but triggered an abrupt increase in the principal tensile strains. It appears that there is a potential risk of pathological fracture for large-sized odontogenic tumour, owing to high tensile stresses and strains.

Role of nanofibers on MSCs fate: Influence of fiber morphologies, compositions and external stimuli.

In regenerative medicine, self-regulated tissue regeneration is perceived by Mesenchymal Stem Cells (MSCs) fate due to their tissue-specific differentiation, which is an emerging yet promising tool for therapeutics. MSCs with their innate nature like secretion of bioactive molecules, multilineage differentiation and proliferation supported tissue repair. MSCs interact with extracellular matrix (ECM) components like collagen, glycosaminoglycans (GAGs), proteoglycans and various proteins that are present in the form of nanofibers representing variable matrix elasticity along with topographies and bioactive cues. Synthetic nanofibers also showed to mimic native tissue microenvironment and supported regeneration owing to structural resemblance with ECM for anchorage-dependent cells. Different nanofibers generated using various polymer precursors and their resultant scaffolds, architectures, compositions etc. were studied for their influence on MSCs activities to improvise cell-cell and cell-material interactions. Electrospinning, popular nanotechnology for fiber formation based on electrohydrodynamic theory, is widely used for many applications due to its simplicity, efficacy and environmentally friendliness. Electrospun nanofibers were extensively investigated to understand the influence of material towards manipulating stem cells based on regenerative medicine. Subsequently, the influence of different solutions and process parameters were studied for nanofiber structure repeatability and emphasized on fiber properties such as diameter, mechanical properties, degradation rate, and porosity. Recent approaches towards scale-up for nanofiber production by electrospinning and other novel techniques are also presented briefly. The fate of MSCs, while seeded on nanofibers under external stimuli viz. electrical, mechanical, magnetic and electromagnetic field, is reviewed to find the niche for differentiation pathways. Further, several external stimuli presented as important factors motivating cellular differentiation in combination with specific conditions without the use of any chemical cues.