Development Of Bioactive Scaffolds Research Articles

Pearl Powder Hybrid Bioactive Scaffolds from Microfluidic 3D Printing for Bone Regeneration.

The development of bioactive scaffolds by mimicking bone tissue extracellular matrix is promising for bone regeneration. Herein, inspired by the bone tissue composition, a novel pearl powder (PP) hybrid fish gelatin methacrylate (GelMa) hydrogel scaffold loaded with vascular endothelial growth factor (VEGF) for bone regeneration is presented. With the help of microfluidic-assisted 3D printing technology, the composition and structure of the hybrid scaffold can be accurately controlled to meet clinical requirements. The combination of fish skin GelMa and PP also endowed the hybrid scaffold with good biocompatibility, cell adhesion, and osteogenic differentiation ability. Moreover, the controlled release of VEGF enables the scaffold to promote angiogenesis. Thus, the bone regeneration in the proposed scaffolds could be accelerated under the synergic effect of osteogenesis and angiogenesis, which has been proved in the rat skull defect model. These features indicate that the PP hybrid scaffolds will be an ideal candidate for bone regeneration in clinical applications.

Novel bioactive collagen-polyurethane-pectin scaffolds for potential application in bone regenerative medicine

Recently, the development of bioactive scaffolds that allow improved bone repair is of interest for hard tissue regenerative medicine strategies. The use of biopolymers with synthetic polymer represents an innovative alternative for this purpose due to its excellent capacity to mimic the bone extracellular matrix. In this work, scaffolds based on bovine tendon collagen and pectin derived from orange (Citrus sinensis) peels were designed. The surfaces were prepared by a polymeric semi-interpenetration process where linear pectin chains were interpenetrated in a polyurethane-crosslinked collagen matrix. The effect of pectin content (10–40 wt.%) on the structural, physicochemical and biological properties of this type of scaffolds was evaluated. The increment in pectin content generates amorphous, granular surfaces with interconnected porosity, improving crosslinking, decreasing swelling and accelerating its rate of degradation in physiological and proteolytic media, also promoting antibacterial capacity showing inhibition of growth of pathogens such as E. coli. Specifically, the scaffold with 20 wt.% pectin (CPc20) shows a mechanical improvement of 342 ± 12% (with respect to crosslinked collagen), allowing the mineralization of 15 ± 1.5% of carbonated apatite on its surface, showing no cytotoxic effects on fibroblasts and allowing their proliferation; in addition, it was determined that immune system cells such as human monocytes can secrete high levels of transforming growth factor beta (TGF-β) and low levels of tumor necrosis factor alpha (TNF-α), conditions required in the process of bone formation. These results demonstrate that these bioactive scaffolds could be applied in bone tissue regenerative medicine strategies.

Chitosan-Based Scaffolds for Facilitated Endogenous Bone Re-Generation.

Facilitated endogenous tissue engineering, as a facile and effective strategy, is emerging for use in bone tissue regeneration. However, the development of bioactive scaffolds with excellent osteo-inductivity to recruit endogenous stem cells homing and differentiation towards lesion areas remains an urgent problem. Chitosan (CS), with versatile qualities including good biocompatibility, biodegradability, and tunable physicochemical and biological properties is undergoing vigorously development in the field of bone repair. Based on this, the review focus on recent advances in chitosan-based scaffolds for facilitated endogenous bone regeneration. Initially, we introduced and compared the facilitated endogenous tissue engineering with traditional tissue engineering. Subsequently, the various CS-based bone repair scaffolds and their fabrication methods were briefly explored. Furthermore, the functional design of CS-based scaffolds in bone endogenous regeneration including biomolecular loading, inorganic nanomaterials hybridization, and physical stimulation was highlighted and discussed. Finally, the major challenges and further research directions of CS-based scaffolds were also elaborated. We hope that this review will provide valuable reference for further bone repair research in the future.

SDF-1 Molecularly Imprinted Biomimetic Scaffold as a Potential Strategy to Repair the Infarcted Myocardium

Background: In situ cardiac tissue engineering aims to heal the infarcted myocardium by guiding tissue regeneration within the patient body. A key step in this approach is the design of a bioactive scaffold, able to stimulate tissue repair at the site of damage. In the development of bioactive scaffolds, molecular imprinting nanotechnology has been recently proposed as a new functionalization strategy. Objectives: In this work, Molecularly Imprinted Particles (MIP) with recognition properties towards the stromal-derived factor-1 (SDF-1) were synthesized, characterized and used for the functionalization of a biomimetic scaffold. MIP are expected to favor the enrichment of the SDF-1 bioactive molecule within the scaffold, thereby promoting myocardial regeneration. Methods: MIP were obtained by precipitation polymerization, using the SDF-1 molecule as a template. Alginate/gelatin/elastin sponges were fabricated by freeze-drying and functionalized by MIP deposition. Morphological, physicochemical and functional analyses were performed both on MIP and on MIP-modified scaffolds. A preliminary biological in vitro investigation was also carried out using rat cardiac progenitor cells (rCPCs). Results: Imprinted nanoparticles with an average diameter between 0.6 and 0.9 µm were obtained. Infrared analysis of MIP confirmed the expected chemical structure. Recognition and selectivity tests showed that MIP were able to selectively recognize and rebind the template, even after their deposition on the scaffold. In vitro biological tests showed that cell adhesion to the scaffold was promoted by MIP functionalization. Conclusion: Results obtained in the present study suggest that biomimetic alginate/gelatin/elastin sponges, functionalized by MIP with recognition properties towards SDF-1, could be successfully used for tissue engineering approaches to repair the infarcted heart.

Three dimensionally printed mesoporous bioactive glass and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) composite scaffolds for bone regeneration.

Development of bioactive scaffolds with controllable architecture and high osteogenic capability for bone tissue engineering is hotly pursued. In this study, three-dimensional (3D) mesoporous bioactive glass (MBG) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds with well-defined pore structures and high compressive strength (∼5-12 MPa) were synthesized by a 3D printing technique. Compared to reported polymer-bonded MBG scaffolds, the incorporation of the biocompatible PHBHHx polymer as a particle binder enhanced their bioactive and osteogenic properties, including fast apatite-forming ability, and promoted human bone marrow-derived mesenchymal stem cell (hBMSC) adhesion, proliferation, alkaline phosphatase (ALP) activity and bone-related gene expression. Furthermore, MBG/PHBHHx composite scaffolds were explored to repair critical-size rat calvarial defects. The results showed that MBG/PHBHHx composite scaffolds exhibited a controlled degradation rate and more significant potential to stabilize the pH environment with increasing PHBHHx ratio. At 8 weeks post-implantation, MBG/PHBHHx scaffolds were demonstrated to stimulate bone regeneration in the calvarial defects and have largely repaired them through analysis of micro-CT, sequential fluorescent labeling and histology. These results lay a potential framework for future study by using modified MBG/PHBHHx-based functional scaffolds to improve the osteogenic activity and bone defect restoration.

Extracellular matrix-mediated osteogenic differentiation of murine embryonic stem cells

Embryonic stem cells (ESCs) are pluripotent and have the ability to differentiate into mineralising cells in vitro. The use of pluripotent cells in engineered bone substitutes will benefit from the development of bioactive scaffolds which encourage cell differentiation and tissue development. Extracellular matrix (ECM) may be a suitable candidate for use in such scaffolds since it plays an active role in cellular differentiation. Here, we test the hypothesis that tissue-specific ECM influences the differentiation of murine ESCs. We induced murine ESCs to differentiate by embryoid body formation, followed by dissociation and culture on ECM prepared by decellularisation of either osteogenic cell (MC3T3-E1) or non-osteogenic cell (A549) cultures, or on defined collagen type I matrix. We assessed osteogenic differentiation by formation of mineralised tissue and osteogenic gene expression, and found it to be significantly greater on MC3T3-E1 matrices than on any other matrix. The osteogenic effect of MC3T3-E1 matrix was reduced by heat treatment and abolished by trypsin, suggesting a bioactive proteinaceous component. These results demonstrate that decellularised bone-specific ECM promotes the osteogenic differentiation of ESCs. Our results are of fundamental interest and may help in tailoring scaffolds for tissue engineering applications which both incorporate tissue-specific ECM signals and stimulate stem-cell differentiation.

Robotic dispensing of composite scaffolds and in vitro responses of bone marrow stromal cells

The development of bioactive scaffolds with a designed pore configuration is of particular importance in bone tissue engineering. In this study, bone scaffolds with a controlled pore structure and a bioactive composition were produced using a robotic dispensing technique. A poly(epsilon-caprolactone) (PCL) and hydroxyapatite (HA) composite solution (PCL/HA = 1) was constructed into a 3-dimensional (3D) porous scaffold by fiber deposition and layer-by-layer assembly using a computer-aided robocasting machine. The in vitro tissue cell compatibility was examined using rat bone marrow stromal cells (rBMSCs). The adhesion and growth of cells onto the robotic dispensed scaffolds were observed to be limited by applying the conventional cell seeding technique. However, the initially adhered cells were viable on the scaffold surface. The alkaline phosphatase activity of the cells was significantly higher on the HA-PCL than on the PCL and control culture dish, suggesting that the robotic dispensed HA-PCL scaffold should stimulate the osteogenic differentiation of rBMSCs. Moreover, the expression of a series of bone-associated genes, including alkaline phosphatase and collagen type I, was highly up-regulated on the HA-PCL scaffold as compared to that on the pure PCL scaffold. Overall, the robotic dispensed HA-PCL is considered to find potential use as a bioactive 3D scaffold for bone tissue engineering.