An aligned fibrous and thermosensitive hyaluronic acid-puramatrix interpenetrating polymer network hydrogel with mechanical properties adjusted for neural tissue

Central nervous system (CNS) injuries such as stroke or trauma can lead to long-lasting disability, and there is no currently accepted treatment to regenerate functional CNS tissue after injury. Hydrogels can mimic the neural extracellular matrix by providing a suitable 3D structure and mechanical properties and have shown great promise in CNS tissue regeneration. Here we present successful synthesis of a thermosensitive hyaluronic acid-RADA 16 (Puramatrix™) peptide interpenetrating network (IPN) that can be applied in situ by injection.Thermosensitive hyaluronic acid (HA) was first synthesized by combining HA with poly(N-isopropylacrylamide). Then, the Puramatrix™ self-assembled peptide was combined with the thermosensitive HA to produce a series of injectable thermoresponsive IPNs. The HA-Puramatrix™ IPNs formed hydrogels successfully at physiological temperature. Characterization by SEM, rheological measurements, enzymatic degradation and swelling tests was performed to select the IPN optimized for neurologic use. SEM images of the optimized dry IPNs demonstrated an aligned porous structure, and the rheological measurements showed that the hydrogels were elastic, with an elastic modulus of approximately 500 Pa, similar to that of brain tissue. An evaluation of the cell–material interactions also showed that the IPN had biological characteristics required for tissue engineering, strongly suggesting that the IPN hydrogel possessed properties beneficial for regeneration of brain tissue.

Fibronectin-Enriched Biomaterials, Biofunctionalization, and Proactivity: A Review

Modern innovation in reconstructive medicine implies the proposition of material-based strategies suitable for tissue repair and regeneration. The development of such systems necessitates the design of advanced materials and the control of their interactions with their surrounding cellular and molecular microenvironments. Biomaterials must actively engage cellular matter to direct and modulate biological responses at implant sites and beyond. Indeed, it is essential that a true dialogue exists between the implanted device and the cells. Biomaterial engineering implies the knowledge and control of cell fate considering the globality of the adhesion process, from initial cell attachment to differentiation. The extracellular matrix (ECM) represents a complex microenvironment able to meet these essential needs to establish a relationship between the material and the contacting cells. The ECM exhibits specific physical, chemical, and biochemical characteristics. Considering the complexity, heterogeneity, and versatility of ECM actors, fibronectin (Fn) has emerged among the ECM protagonists as the most pertinent representative key actor. The following review focuses on and synthesizes the research supporting the potential to use Fn in biomaterial functionalization to mimic the ECM and enhance cell–material interactions.

Hierarchically Structured Polystyrene-Based Surfaces Amplifying Fluorescence Signals: Cytocompatibility with Human Induced Pluripotent Stem Cell

An innovative multi-step phase separation process was used to prepare tissue culture for the polystyrene-based, hierarchically structured substrates, which mimicked in vivo microenvironment and architecture. Macro- (pore area from 3000 to 18,000 µm2; roughness (Ra) 7.2 ± 0.1 µm) and meso- (pore area from 50 to 300 µm2; Ra 1.1 ± 0.1 µm) structured substrates covered with micro-pores (area around 3 µm2) were prepared and characterised. Both types of substrate were suitable for human-induced pluripotent stem cell (hiPSC) cultivation and were found to be beneficial for the induction of cardiomyogenesis in hiPSC. This was confirmed both by the number of promoted proliferated cells and the expressions of specific markers (Nkx2.5, MYH6, MYL2, and MYL7). Moreover, the substrates amplified the fluorescence signal when Ca2+ flow was monitored. This property, together with cytocompatibility, make this material especially suitable for in vitro studies of cell/material interactions within tissue-mimicking environments.

Multiblock copolymers type PDC- a family of multifunctional biomaterials for regenerative medicine1

Multiblock copolymers type PDC are polyetheresterurethanes composed of poly(ɛ-caprolactone) and poly(p-dioxanone) segments. They were designed as degradadable shape-memory polymers for medical devices, which can be implanted minimally-invasively. While providing structural support in the initial phase after implantation, they are capable to modulate soft tissue regeneration while degradation. In this perspective, we elucidate cell-material interactions, compatibility both in-vitro and in-vivo and biofunctionality of PDC, which represents a promising candidate biomaterial family especially for cardiovascular applications.

Advanced Bio-Based Polymers for Astrocyte Cell Models

The development of in vitro neural tissue analogs is of great interest for many biomedical engineering applications, including the tissue engineering of neural interfaces, treatment of neurodegenerative diseases, and in vitro evaluation of cell–material interactions. Since astrocytes play a crucial role in the regenerative processes of the central nervous system, the development of biomaterials that interact favorably with astrocytes is of great research interest. The sources of human astrocytes, suitable natural biomaterials, guidance scaffolds, and ligand patterned surfaces are discussed in the article. New findings in this field are essential for the future treatment of spinal cord and brain injuries.

Beta-Catenin Limits Osteogenesis on Regenerative Materials in a Stiffness-Dependent Manner

Targeted refinement of regenerative materials requires mechanistic understanding of cell-material interactions. The nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) scaffold is a porous biomaterial that promotes regenerative healing of calvaria defects in vivo without addition of exogenous growth factors or progenitor cells, suggesting its potential as an off-the-shelf implant for reconstructing skull defects. In this work, we evaluate the relationship between material stiffness, a tunable MC-GAG property, and activation of the canonical Wnt (cWnt) signaling pathway. Primary human bone marrow-derived mesenchymal stem cells (hMSCs) were differentiated on two MC-GAG scaffolds varying by stiffness (non-crosslinked, NX-MC, 0.3 kPa vs. conventionally crosslinked, MC, 3.9 kPa). hMSCs exhibited increased expression of activated β-catenin, the major cWnt intracellular mediator, and the mechanosensitive YAP protein with near complete subcellular colocalization in stiffer MC scaffolds. Small molecule Wnt pathway inhibitors reduced activated β-catenin and YAP protein quantities and colocalization, osteogenic differentiation, and mineralization on MC, with no effects on NX-MC. Concomitantly, Wnt inhibitors increased BMP4 and phosphorylated Smad1/5 (p-Smad1/5) expression on MC, but not NX-MC. Unlike non-specific Wnt pathway downregulation, isolated canonical Wnt inhibition with β-catenin knockdown increased osteogenic gene expression and mineralization specifically on the stiffer MC. β-catenin knockdown also increased p-Smad1/5, Runx2, and BMP4 expression only on the stiffer MC material. Our data indicates stiffness-induced activation of the Wnt and mechanotransduction pathways promotes osteogenesis in MC-GAG scaffolds. However, activated β-catenin is a limiting agent and may serve as a useful target or readout for optimal modulation of stiffness in skeletal regenerative materials.

Characterization and evaluation of a femtosecond laser-induced osseointegration and an anti-inflammatory structure generated on a titanium alloy

Cell–material interactions during early osseointegration of the bone–implant interface are critical and involve crosstalk between osteoblasts and osteoclasts. The surface properties of titanium implants also play a critical role in cell–material interactions. In this study, femtosecond laser treatment and sandblasting were used to alter the surface morphology, roughness and wettability of a titanium alloy. Osteoblasts and osteoclasts were then cultured on the resulting titanium alloy disks. Four disk groups were tested: a polished titanium alloy (pTi) control; a hydrophilic micro-dislocation titanium alloy (sandblasted Ti (STi)); a hydrophobic nano-mastoid Ti alloy (femtosecond laser-treated Ti (FTi)); and a hydrophilic hierarchical hybrid micro-/nanostructured Ti alloy [femtosecond laser-treated and sandblasted Ti (FSTi)]. The titanium surface treated by the femtosecond laser and sandblasting showed higher biomineralization activity and lower cytotoxicity in simulated body fluid and lactate dehydrogenase assays. Compared to the control surface, the multifunctional titanium surface induced a better cellular response in terms of proliferation, differentiation, mineralization and collagen secretion. Further investigation of macrophage polarization revealed that increased anti-inflammatory factor secretion and decreased proinflammatory factor secretion occurred in the early response of macrophages. Based on the above results, the synergistic effect of the surface properties produced an excellent cellular response at the bone–implant interface, which was mainly reflected by the promotion of early ossteointegration and macrophage polarization.