Human-based fibrillar nanocomposite hydrogels as bioinstructive matrices to tune stem cell behavior

Abstract

The extracellular matrix (ECM)-biomimetic fibrillar structure of platelet lysate (PL) gels along with their enriched milieu of biomolecules has drawn significant interest in regenerative medicine applications. However, PL-based gels have poor structural stability, which severely limits their performance as a bioinstructive biomaterial. Here, rod-shaped cellulose nanocrystals (CNC) are used as a novel approach to modulate the physical and biochemical microenvironment of PL gels enabling their effective use as injectable human-based cell scaffolds with a level of biomimicry that is difficult to recreate with synthetic biomaterials. The incorporation of CNC (0 to 0.61 wt%) into the PL fibrillar network during the coagulation cascade leads to decreased fiber branching, increased interfiber porosity (from 66 to 83%) and modulates fiber (from 1.4 ± 0.7 to 27 ± 12 kPa) and bulk hydrogel (from 18 ± 4 to 1256 ± 82 Pa) mechanical properties. As a result of these physicochemical alterations, nanocomposite PL hydrogels resist the typical extensive clot retraction (from 76 ± 1 to 24 ± 3 at day 7) and show favored retention of PL bioactive molecules. The feedback of these cues on the fate of human adipose-derived stem cells is evaluated, showing how it can be explored to modulate the commitment of encapsulated stem cells toward different genetic phenotypes without the need for additional external biological stimuli. These fibrillar nanocomposite hydrogels allow therefore the exploration of the outstanding biological properties of human-based PL as an efficient engineered ECM which can be tailored to trigger specific regenerative pathways in minimal invasive strategies.

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

“…The development of injectable hydrogel systems with control over the architecture of the fibrillar network has been also demonstrated to have biological relevance [32]. These hydrogels have a controllable and precise internal fibrous structure, which determines their pore size and mechanical properties, while replicating the filamentous architecture of the ECM.…”

Fabrication and properties of an injectable sodium alginate/PRP composite hydrogel as a potential cell carrier for cartilage repair

“…Thus, PRP has been regarded as an appealing alternative to the use of immunologically‐risky and expensive recombinant growth factors in different clinical settings to improve healing of dental implants, bone fractures, and others (Marx, ). Recently, PRP has been also used as component of gels and scaffolds for sustained release of growth factors in different tissue engineering applications (Diaz‐Gomez et al, ; Kutlu, Tiğlı Aydın, Akman, Gümüşderelioglu, & Nohutcu, ; Mendes et al, ). Platelet‐derived growth factors include also those that enhance growth and differentiation of chondrogenic cells, such as transforming growth factor (TGF‐β1) and platelet‐derived growth factor (PDGF; Xie et al, ).…”

Exploring platelet lysate hydrogel-coated suture threads as biofunctional composite living fibers for cell delivery in tissue repair

“…As a proof-of-concept study, we developed a coating strategy and further assessed the Hydrogels based on PL have been increasingly investigated either employing selfcrosslinking mechanisms [17][18][19] or incorporating PL in hydrogel matrices [31][32][33].…”

“…Different incubation times were tested to evaluate their influence on the formation of PL hydrogel coating. Subsequently, suture threads were immersed in PL solution and incubated for 2 hours at 37°C, as previously described [19]. The presence of these clotting factors induces a rapid selfassembly of PL into a 3D hydrogel [17].…”

“…Particularly, PL can be obtained from platelet concentrates by the cryogenic disruption of platelets and constitutes a protein-rich cocktail comprising several growth factors (e.g., platelet-derived growth factor (PDGF), transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF), among others) and molecules A c c e p t e d M a n u s c r i p t 4 involved in cell adhesion (e.g., fibrin, fibronectin and vitronectin) [14,15]. PLderived biomaterials, including hydrogels [17][18][19][20], scaffolds [21][22][23] and patches [24,25], have been receiving great attention toward overcoming some limitations associated to bolus injections of therapeutic growth factors or platelet-derived preparations (e.g., rapid leakage, short half-life of soluble factors, denaturation, injection risks, etc. ), constituting a promising strategy for endogenous regenerative medicine.…”