Autologous Oxygen-Releasing Nano-Biomimetic Scaffold with Chondrocytes Promotes Joint Repair After Trauma

Our study assesses the role of a scaffold constructed by co-culture of autologous oxygen-releasing biomimetic scaffold (AONS) and chondrocytes in joint repair after trauma. A composite scaffold structure was used and a scaffold constructed of AONS and chondrocytes was transplanted into SD rats to create models of patellar cartilage fracture and hip osteochondral fracture, respectively followed by analysis of cell proliferation by immunofluorescence method, osteogenesis-related gene expression by RT-PCR, chondrocytes apoptosis by TUNEL staining. The blank control group and AONS composite chondrocytes have significant differences in apoptosis and cell proliferation of two fracture types (P <0.05). The autologous oxygen-releasing nanometers at 4 and 8 weeks showed a significant difference in the number of PCNA and TUNEL cells between biomimetic scaffold and chondrocytes in two groups (P < 0.05). The AONS and chondrocytes were effective for two types of fractures at 1, 4 and 8 weeks. The expression of various markers of intrachondral osteogenesis was decreased and the markers of hip osteochondral fracture were increased significantly (P < 0.05). Joint recovery was better than patellar cartilage fractures. The AONS composite chondrocyte scaffold promotes repair of patellar cartilage fractures and hip osteochondral fractures with a better effect on hip osteochondral fractures.

Bioactive molecules for regenerative pulp capping

Since the discovery of bioactive molecules sequestered in dentine, researchers have been exploring ways to harness their activities for dental regeneration. One specific area, discussed in this review, is that of dental-pulp capping. Dental-pulp caps are placed when the dental pulp is exposed due to decay or trauma in an attempt to enhance tertiary dentine deposition. Several materials are used for dental-pulp capping; however, natural biomimetic scaffolds may offer advantages over manufactured materials such as improved aesthetic, biocompatibility and success rate. The present review discusses and appraises the current evidence surrounding biomimetic dental-pulp capping, with a focus on bioactive molecules sequestered in dentine. Molecules covered most extensively in the literature include transforming growth factors (TGF-βs, specifically TGF-β1) and bone morphogenetic proteins (BMPs, specifically BMP-2 and BMP-7). Further studies would need to explore the synergistic use of multiple peptides together with the development of a tailored scaffold carrier. The roles of some of the molecules identified in dentine need to be explored before they can be considered as potential bioactive molecules in a biomimetic scaffold for dental-pulp capping. Future in vivo work needs to consider the inflammatory environment of the dental pulp in pulpal exposures and compare pulp-capping materials.

A bioinspired scaffold for rapid oxygenation of cell encapsulation systems

Inadequate oxygenation is a major challenge in cell encapsulation, a therapy which holds potential to treat many diseases including type I diabetes. In such systems, cellular oxygen (O2) delivery is limited to slow passive diffusion from transplantation sites through the poorly O2-soluble encapsulating matrix, usually a hydrogel. This constrains the maximum permitted distance between the encapsulated cells and host site to within a few hundred micrometers to ensure cellular function. Inspired by the natural gas-phase tracheal O2 delivery system of insects, we present herein the design of a biomimetic scaffold featuring internal continuous air channels endowed with 10,000-fold higher O2 diffusivity than hydrogels. We incorporate the scaffold into a bulk hydrogel containing cells, which facilitates rapid O2 transport through the whole system to cells several millimeters away from the device-host boundary. A computational model, validated by in vitro analysis, predicts that cells and islets maintain high viability even in a thick (6.6 mm) device. Finally, the therapeutic potential of the device is demonstrated through the correction of diabetes in immunocompetent mice using rat islets for over 6 months.

Boost Tendon/Ligament Repair With Biomimetic and Smart Cellular Constructs

Tendon and ligament are soft connective tissues that play essential roles in transmitting forces from muscle to bone or bone to bone. Despite significant progress made in the field of ligament and tendon regeneration over the past decades, many strategies struggle to recapitulate basic structure-function criteria of native ligament/tendon. The goal here is to provide a fundamental understanding of the structure and composition of ligament/tendon and highlight few key challenges in functional regeneration of these connective tissues. The remainder of the review will examine several biomaterials strategies including biomimetic scaffold with non-linear mechanical behavior, hydrogel patch with anisotropic adhesion and gene-activated scaffold for interactive healing of tendon/ligament. Finally, emerging technologies and research avenues are suggested that have the potential to enhance treatment outcomes of tendon/ligament injuries.

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.

Adipose-Derived Stem Cells Based on Electrospun Biomimetic Scaffold Mediated Endothelial Differentiation Facilitating Regeneration and Repair of Abdominal Wall Defects via HIF-1α/VEGF Pathway

Application of synthetic or biological meshes is the main therapy for the repair and reconstruction of abdominal wall defects, a common disease in surgery. Currently, no ideal materials are available, and there is an urgent need to find appropriate ones to satisfy clinical needs. Electrospun scaffolds have drawn attention in soft tissue reconstruction. In this study, we developed a novel method to fabricate a composite electrospun scaffold using a thermoresponsive hydrogel, poly (N-isopropylacrylamide)-block-poly (ethylene glycol), and a biodegradable polymer, polylactic acid (PLA). This scaffold provided not only a high surface area/volume ratio and a three-dimensional fibrous matrix but also high biocompatibility and sufficient mechanical strength, and could simulate the native extracellular matrix and accelerate cell adhesion and proliferation. Furthermore, rat adipose-derived stem cells (ADSCs) were seeded in the composite electrospun scaffold to enhance the defect repair and regeneration by directionally inducing ADSCs into endothelial cells. In addition, we found early vascularization in the process was regulated by the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. In our study, overexpression of HIF-1α/VEGF in ADSCs using a lentivirus system promoted early vascularization in the electrospun scaffolds. Overall, we expect our composite biomimetic scaffold method will be applicable and useful in abdominal wall defect regeneration and repair in the future.