Advances in cell-laden hydrogels for delivering therapeutics

Almost six decades ago, a visionary scientist reported a new method for encapsulating aqueous solutions of protein within semipermeable polymer membranes [1]. This approach was successfully tested in the 1970s and 1980s by immobilizing xenograft islet cells to control glucose metabolism in small animal models [2,3]. Since then, the concept of cell-laden hydrogels has evolved and progressed but still those pioneering works are perfect examples of the theoretical advantages that this approach may offer in terms of long-term delivery and immune protection [4]. In its most basic form, cell-laden hydrogels or bioartificial organs consist of a polymeric or synthetic membrane structure that entraps a wide range of cells releasing bioactive drugs or proteins [5,6]. The three-dimensional (3D) constructs, typically either shaped as a microcapsule or a hollow-fiber, will regulate with different efficiency the permeability and mechanical stability of the cell-based medicine [7]. The semipermeable membrane is responsible for preventing high molecular weight molecules, antibodies and other immunologic components from entering within the construct but also controls the inward/outward diffusion of critical agents for cell survival and therapeutic efficacy including nutrients, oxygen, waste agents and therapeutic protein products (Figure 1). Even though the journey from theory to practice has been demanding and challenging, recent progress in the field is creating new avenues of hope to use this approach in several unmet clinical needs ranging from diabetes to ophthalmological disorders or rare diseases

Tissue-specific melt electrowritten polymeric scaffolds for coordinated regeneration of soft and hard periodontal tissues

Periodontitis is a chronic inflammatory condition that often causes serious damage to tooth-supporting tissues. The limited successful outcomes of clinically available approaches underscore the need for therapeutics that cannot only provide structural guidance to cells but can also modulate the local immune response. Here, three-dimensional melt electrowritten ( i.e., poly(ε-caprolactone)) scaffolds with tissue-specific attributes were engineered to guide differentiation of human-derived periodontal ligament stem cells (hPDLSCs) and mediate macrophage polarization. The investigated tissue-specific scaffold attributes comprised fiber morphology (aligned vs. random) and highly-ordered architectures with distinct strand spacings (small 250 μm and large 500 μm). Macrophages exhibited an elongated morphology in aligned and highly-ordered scaffolds, while maintaining their round-shape on randomly-oriented fibrous scaffolds. Expressions of periostin and IL-10 were more pronounced on the aligned and highly-ordered scaffolds. While hPDLSCs on the scaffolds with 500 μm strand spacing show higher expression of osteogenic marker (Runx2) over 21 days, cells on randomly-oriented fibrous scaffolds showed upregulation of M1 markers. In an orthotopic mandibular fenestration defect model, findings revealed that the tissue-specific scaffolds ( i.e., aligned fibers for periodontal ligament and highly-ordered 500 μm strand spacing fluorinated calcium phosphate [F/CaP]-coated fibers for bone) could enhance the mimicking of regeneration of natural periodontal tissues

Towards 3D fabrication of MgP-based mechanically competent implants for bone regeneration

The development of the degradable bone implants has gained a great attention during the last years. This need comes from the fact that autologous bone transplantation, which is the current standard and most effective treatment of bone defects, is associated with severe drawbacks regarding donor site morbidity and limited availability. However, there is a lack of synthetic materials that are degradable, osteopromotive and mechanically competent at the same time. Further, materials processing and the implantation of the scaffolds in the body are also an important challenge. In this thesis, by using advanced 3D printing technologies, the fabrication of biodegradable, patient-specific, and mechanically competent MgP-based implants has been explored to treat critical-sized bone defects. The developed MgP-based biomaterial is inspired by the composition of native bone tissue and can be degraded in the body and subsequently be replaced by native bone

Injectable and adhesive hydrogels for dealing with wounds

INTRODUCTION: The development of wound dressing materials that combine healing properties, ability to self-repair the material damages, skin-friendly adhesive nature, and competent mechanical properties have surpassing functional importance in healthcare. Due to their specificity, hydrogels have been recognized as a new gateway in biological materials to treat dysfunctional tissues. The design and creation of injectable hydrogel-based scaffolds have extensively progressed in recent years to improve their therapeutic efficacy and to pave the way for their easy minimally invasive administration. Hence, injectable hydrogel biomaterials have been prepared to eventually translate into minimally invasive therapy and pose a lasting effect on regenerative medicine. AREAS COVERED: This review highlights the recent development of adhesive and injectable hydrogels that have applications in wound healing and wound dressing. Such hydrogel materials are not only expected to improve therapeutic outcomes but also to facilitate the easy surgical process in both wound healing and dressing. EXPERT OPINION: Wound healing seems to be an appealing approach for treating countless life-threatening disorders. With the average increase of life expectancy in human societies, an increase in demand for injectable skin replacements and drug delivery carriers for chronic wound healing is expected

Stable and Antibacterial Magnesium-Graphene Nanocomposite-Based Implants for Bone Repair

Magnesium (Mg)-based alloys are promising biodegradable materials for bone repair applications. However, due to their rapid degradation and high corrosion rate, Mg-based alloys are typically associated with in vivo infections and implant failure. This study evaluated the synergistic stability and anti-inflammatory properties that could potentially be achieved by the modification of the Mg alloy with graphene nanoparticles (Gr). Incorporation of low dosages of Gr (0.18 and 0.50 wt %) in a Mg alloy with aluminum (Al, 1 wt %) and copper (Cu, 0.25 wt %) was successfully achieved by a spark plasma sintering (SPS) method. Notably, the degradation rate of the Mg-based alloys was reduced approximately 4-fold and the bactericidal activity was enhanced up to 5-fold with incorporation of only 0.18 wt % Gr to the Mg-1Al-Cu matrix. Moreover, the modified Mg-based nanocomposites with 0.18 wt % Gr demonstrated compressive properties within the range of native cancellous bone (modulus of approximately 6 GPa), whereas in vitro studies with human mesenchymal stromal cells (hMSCs) showed high cytocompatibility and superior osteogenic properties compared to non-Gr-modified Mg-1Al-Cu implants. Overall, this study provides foundations for the fabrication of stable, yet fully resorbable, Mg-based bone implants that could reduce implant-associated infections

Stable and Antibacterial Magnesium-Graphene Nanocomposite-Based Implants for Bone Repair

Magnesium (Mg)-based alloys are promising biodegradable materials for bone repair applications. However, due to their rapid degradation and high corrosion rate, Mg-based alloys are typically associated with in vivo infections and implant failure. This study evaluated the synergistic stability and anti-inflammatory properties that could potentially be achieved by the modification of the Mg alloy with graphene nanoparticles (Gr). Incorporation of low dosages of Gr (0.18 and 0.50 wt %) in a Mg alloy with aluminum (Al, 1 wt %) and copper (Cu, 0.25 wt %) was successfully achieved by a spark plasma sintering (SPS) method. Notably, the degradation rate of the Mg-based alloys was reduced approximately 4-fold and the bactericidal activity was enhanced up to 5-fold with incorporation of only 0.18 wt % Gr to the Mg–1Al–Cu matrix. Moreover, the modified Mg-based nanocomposites with 0.18 wt % Gr demonstrated compressive properties within the range of native cancellous bone (modulus of approximately 6 GPa), whereas in vitro studies with human mesenchymal stromal cells (hMSCs) showed high cytocompatibility and superior osteogenic properties compared to non-Gr-modified Mg–1Al–Cu implants. Overall, this study provides foundations for the fabrication of stable, yet fully resorbable, Mg-based bone implants that could reduce implant-associated infections

Injectable hydrogels for cartilage and bone tissue regeneration:A review

Annually, millions of patients suffer from irreversible injury owing to the loss or failure of an organ or tissue caused by accident, aging, or disease. The combination of injectable hydrogels and the science of stem cells have emerged to address this persistent issue in society by generating minimally invasive treatments to augment tissue function. Hydrogels are composed of a cross-linked network of polymers that exhibit a high-water retention capacity, thereby mimicking the wet environment of native cells. Due to their inherent mechanical softness, hydrogels can be used as needle-injectable stem cell carrier materials to mend tissue defects. Hydrogels are made of different natural or synthetic polymers, displaying a broad portfolio of eligible properties, which include biocompatibility, low cytotoxicity, shear-thinning properties as well as tunable biological and physicochemical properties. Presently, novel ongoing developments and native-like hydrogels are increasingly being used broadly to improve the quality of life of those with disabling tissue-related diseases. The present review outlines various future and in-vitro applications of injectable hydrogel-based biomaterials, focusing on the newest ongoing developments of in-situ forming injectable hydrogels for bone and cartilage tissue engineering purposes.</p

Multi-leveled Nanosilicate Implants Can Facilitate Near-Perfect Bone Healing

Several studies have shown that nanosilicate-reinforced scaffolds are suitable for bone regeneration. However, hydrogels are inherently too soft for load-bearing bone defects of critical sizes, and hard scaffolds typically do not provide a suitable three-dimensional (3D) microenvironment for cells to thrive, grow, and differentiate naturally. In this study, we bypass these long-standing challenges by fabricating a cell-free multi-level implant consisting of a porous and hard bone-like framework capable of providing load-bearing support and a softer native-like phase that has been reinforced with nanosilicates. The system was tested with rat bone marrow mesenchymal stem cells in vitro and as a cell-free system in a critical-sized rat bone defect. Overall, our combinatorial and multi-level implant design displayed remarkable osteoconductivity in vitro without differentiation factors, expressing significant levels of osteogenic markers compared to unmodified groups. Moreover, after 8 weeks of implantation, histological and immunohistochemical assays indicated that the cell-free scaffolds enhanced bone repair up to approximately 84% following a near-complete defect healing. Overall, our results suggest that the proposed nanosilicate bioceramic implant could herald a new age in the field of orthopedics.</p