Integrated printed BDNF-stimulated HUCMSCs-derived exosomes/collagen/chitosan biological scaffolds with 3D printing technology promoted the remodelling of neural networks after traumatic brain injury

Abstract

The restoration of nerve dysfunction after traumatic brain injury (TBI) faces huge challenges due to the limited self-regenerative abilities of nerve tissues. In situ inductive recovery can be achieved utilizing biological scaffolds combined with endogenous human umbilical cord mesenchymal stem cells (HUCMSCs)-derived exosomes (MExos). In this study, brain derived neurotrophic factor (BDNF)-stimulated HUCMSCs-derived exosomes (BMExos) were composited with collagen/chitosan by 3D printing technology. 3D-printed collagen/chitosan/BMExos (3D-CC-BMExos) scaffolds have excellent mechanical properties and biocompatibility. Subsequently, in vivo experiments showed that 3D-CC-BMExos therapy could improve the recovery of neuromotor function and cognitive function in a TBI model in rats. Consistent with the behavioral recovery, the results of histomorphological tests showed that 3D-CC-BMExos therapy could facilitate the remodelling of neural networks, such as improving the regeneration of nerve fibers, synaptic connections and myelin sheaths, in lesions after TBI.

Recent advances and future directions of 3D to 6D printing in brain cancer treatment and neural tissue engineering

“…In vivo experiments on rats demonstrated that 3D-CC-BMExos therapy improved neuromotor and cognitive function in TBI models, facilitated the regeneration of nerve fibers, synaptic connections, and myelin sheaths in TBI lesions [67].…”

“…Liu et al [67] conducted a study to evaluate scaffolds made of collagen, chitosan, and exosomes derived from human umbilical cord MSCs using 3D printing technology. These scaffolds were referred to as 3D-CC-BMExos and exhibited exceptional mechanical properties and biocompatibility.…”

Biomaterial strategies for regulating the neuroinflammatory response

“…New insights into the underlying mechanisms of neuroinflammation have prompted the design of novel biomaterials to mitigate the detrimental effects of excessive inflammation and protect surrounding CNS tissue from secondary damage. Recent advances have been made in a variety of biomaterial strategies for modulating neuroinflammation, including nanoparticles with the ability to cross the selectively permeable BBB/ BSCB, [116][117][118] hydrogels that enable controlled delivery of immunomodulatory therapeutics, 119,120 implantable scaffolds with biophysical cues to enhance cellular alignment and promote a growth-permissive environment for neural regeneration, [121][122][123][124][125] and biomaterial coatings to prolong the lifetime of neural probe implants. 32,[126][127][128]…”

Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions

“…A notable application of this strategy involves the use of biological scaffolds combined with EVs derived from HUCMSCs, specifically engineered for in situ inductive recovery. In a pioneering study by Liu et al, exosomes from BDNF-stimulated HUCMSCs (BMExos) were incorporated into collagen/chitosan scaffolds via 3D printing [ 290 ]. These scaffolds, which have outstanding mechanical properties and biocompatibility, were shown in vivo to significantly improve neuromotor and cognitive abilities in a rat TBI model, demonstrating the promise of integrating exosomes with advanced bio-nanomaterials for neural repair.…”