Current multi-scale biomaterials for tissue regeneration following spinal cord injury.

Spinal cord injury (SCI) may cause loss of motor and sensory function, autonomic dysfunction, and thus disrupt the quality of life of patients, leading to severe disability and significant psychological, social, and economic burden. At present, existing therapy for SCI have limited ability to promote neural function recovery, and there is an urgent need to develop innovative regenerative approaches to repair SCI. Biomaterials have become a promising strategy to promote the regeneration and repair of damaged nerve tissue after SCI. Biomaterials can provide support for nerve tissue by filling cavities, and improve local inflammatory responses and reshape extracellular matrix structures through unique biochemical properties to create the optimal microenvironment at the SCI site, thereby promoting neurogenesis and reconnecting damaged spinal cord tissue. Considering the importance of biomaterials in repairing SCI, this article reviews the latest progress of multi-scale biomaterials in SCI treatment and tissue regeneration, and evaluates the relevant technologies for manufacturing biomaterials.

Swelling-Mediated Mechanical Stimulation Regulates Differentiation of Adipose-Derived Mesenchymal Stem Cells for Intervertebral Disc Repair Using Injectable UCST Microgels.

Mechanical stimulation is an effective approach for controlling stem cell differentiation in tissue engineering. However, its realization in in vivo tissue repair remains challenging since this type of stimulation can hardly be applied to injectable seeding systems. Here, it is presented that swelling of injectable microgels can be transformed to in situ mechanical stimulation via stretching the cells adhered on their surface. Poly(acrylamide-co-acrylic acid) microgels with the upper critical solution temperature property are fabricated using inverse emulsion polymerization and further coated with polydopamine to increase cell adhesion. Adipose-derived mesenchymal stem cells (ADSCs) adhered on the microgels can be omnidirectionally stretched along with the responsive swelling of the microgels, which upregulate TRPV4 and Piezo1 channel proteins and enhance nucleus pulposus (NP)-like differentiation of ADSCs. In vivo experiments reveal that the disc height and extracellular matrix content of NP are promoted after the implantation with the microgels. The findings indicate that swelling-induced mechanical stimulation has great potential for regulating stem cell differentiation during intervertebral disc repair.

Heterozygous mutation of c.3521C>T in COL1A1 may cause mild osteogenesis imperfecta/Ehlers-Danlos syndrome in a Chinese family.

Osteogenesis imperfecta (OI) is an inheritable connective tissue disorder with a broad clinical heterozygosis, which can be complicated by other connective tissue disorders like Ehlers-Danlos syndrome (EDS). OI/EDS are rarely documented. Most OI/EDS mutations are located in the N-anchor region of type I procollagen and predominated by glycine substitution. We identified a c.3521C>T (p.A1174V) heterozygous mutation in COL1A1 gene in a four-generation pedigree with proposed mild OI/EDS phenotype. The affected individuals had blue sclera and dentinogenesis imperfecta (DI) was uniformly absent. The OI phenotype varied from mild to moderate, with the absence of scoliosis and increased skin extensibility. Easy bruising, joint dislocations and high Beighton score were present in some affected individuals. EDS phenotype is either mild or unremarkable in some individuals. The mutation is poorly conserved and in silico prediction support the relatively mild phenotype. The molecular mechanisms of the mutation that leads to the possible OI/EDS phenotype should be further identified by biochemical analysis of N-propeptide processing and steady state collagen analysis.