Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Its pathophysiology comprises acute and chronic phases and incorporates a cascade of destructive events such as ischemia, oxidative stress, inflammatory events, apoptotic pathways and locomotor dysfunctions. Many therapeutic strategies have been proposed to overcome neurodegenerative events and reduce secondary neuronal damage. Efforts have also been devoted in developing neuroprotective and neuro-regenerative therapies that promote neuronal recovery and outcome. Although varying degrees of success have been achieved, curative accomplishment is still elusive probably due to the complex healing and protective mechanisms involved. Thus, current understanding in this area must be assessed to formulate appropriate treatment modalities to improve SCI recovery. This review aims to promote the understanding of SCI pathophysiology, interrelated or interlinked multimolecular interactions and various methods of neuronal recovery i.e., neuroprotective, immunomodulatory and neuro-regenerative pathways and relevant approaches.

Probiotics are live microorganisms that exert beneficial effects on the host, when administered in adequate amounts. Mostly, probiotics affect the gastrointestinal (GI) tract of the host and alter the composition of gut microbiota. Nowadays, the incidence of hip fractures due to osteoporosis is increasing worldwide. Ovariectomized (OVX) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women. Therefore, this study aimed to examine the effects ofBifidobacterium longum(B. longum) on bone mass density (BMD), bone mineral content (BMC), bone remodeling, bone structure, and gene expression in OVX rats. The rats were randomly assigned into 3 groups (sham, OVX, and the OVX group supplemented with 1 mL ofB. longum10⁸–10⁹colony forming units (CFU)/mL).B. longumwas given once daily for 16 weeks, starting from 2 weeks after the surgery. TheB. longumsupplementation increased (p<0.05) serum osteocalcin (OC) and osteoblasts, bone formation parameters, and decreased serum C-terminal telopeptide (CTX) and osteoclasts, bone resorption parameters. It also altered the microstructure of the femur. Consequently, it increased BMD by increasing (p<0.05) the expression ofSparcandBmp-2genes.B. longumalleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation.

Vitamin E belongs to the family of lipid-soluble vitamins and can be divided into two groups, tocopherols and tocotrienols, with four isomers (alpha, beta, gamma and delta). Although vitamin E is widely known as a potent antioxidant, studies have also revealed that vitamin E possesses anti-inflammatory properties. These crucial properties of vitamin E are beneficial in various aspects of health, especially in neuroprotection and cardiovascular, skin and bone health. However, the poor bioavailability of vitamin E, especially tocotrienols, remains a great limitation for clinical applications. Recently, nanoformulations that include nanovesicles, solid-lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and polymeric nanoparticles have shown promising outcomes in improving the efficacy and bioavailability of vitamin E. This review focuses on the pharmacological properties and pharmacokinetics of vitamin E and current advances in vitamin E nanoformulations for future clinical applications. The limitations and future recommendations are also discussed in this review.

Extracellular vesicles (EVs) are minute vesicles with lipid bilayer membranes. EVs are secreted by cells for intercellular communication. Recently, EVs have received much attention, as they are rich in biological components such as nucleic acids, lipids, and proteins that play essential roles in tissue regeneration and disease modification. In addition, EVs can be developed as vaccines against cancer and infectious diseases, as the vesicle membrane has an abundance of antigenic determinants and virulent factors. EVs for therapeutic applications are typically collected from conditioned media of cultured cells. However, the number of EVs secreted by the cells is limited. Thus, it is critical to devise new strategies for the large-scale production of EVs. Here, we discussed the strategies utilized by researchers for the scalable production of EVs. Techniques such as bioreactors, mechanical stimulation, electrical stimulation, thermal stimulation, magnetic field stimulation, topographic clue, hypoxia, serum deprivation, pH modification, exposure to small molecules, exposure to nanoparticles, increasing the intracellular calcium concentration, and genetic modification have been used to improve the secretion of EVs by cultured cells. In addition, nitrogen cavitation, porous membrane extrusion, and sonication have been utilized to prepare EV-mimetic nanovesicles that share many characteristics with naturally secreted EVs. Apart from inducing EV production, these upscaling interventions have also been reported to modify the EVs’ cargo and thus their functionality and therapeutic potential. In summary, it is imperative to identify a reliable upscaling technique that can produce large quantities of EVs consistently. Ideally, the produced EVs should also possess cargo with improved therapeutic potential.

Three-dimensional bioprinting has rapidly paralleled many biomedical applications and assisted in advancing the printing of complex human organs for a better therapeutic practice. The objective of this systematic review is to highlight evidence from the existing studies and evaluate the effectiveness of using natural-based bioinks in skin regeneration and wound healing. A comprehensive search of all relevant original articles was performed based on prespecified eligibility criteria. The search was carried out using PubMed, Web of Science, Scopus, Medline Ovid, and ScienceDirect. Eighteen articles fulfilled the inclusion and exclusion criteria. The animal studies included a total of 151 animals with wound defects. A variety of natural bioinks and skin living cells were implanted in vitro to give insight into the technique through different assessments and findings. Collagen and gelatin hydrogels were most commonly used as bioinks. The follow-up period ranged between one day and six weeks. The majority of animal studies reported that full wound closure was achieved after 2–4 weeks. The results of both in vitro cell culture and in vivo animal studies showed the positive impact of natural bioinks in promoting wound healing. Future research should be focused more on direct the bioprinting of skin wound treatments on animal models to open doors for human clinical trials.

Background: Proteins are commonly used in the healthcare industry to treat various health conditions, and most proteins are sensitive to physical and chemical changes. Lyophilization, also known as freeze-drying, involves sublimating water in the form of ice from a substance at low pressure, forming a freeze-dried powder that increases its shelf life. Extreme pressure and varying temperatures in the freeze-drying process may damage the protein’s structural integrity. Lyoprotectants are commonly used to protect protein conformations. It is important to choose a suitable lyoprotectant to ensure optimal effectiveness. Method: Twenty articles screened from Scopus, Web of Science, and PubMed were included in this review that discussed potential lyoprotectants and their effectiveness with different protein models. Results: Lyoprotectants were categorized into sugars, polyols, surfactants, and amino acids. Lyoprotectants can exhibit significant protective effects towards proteins, either singularly or in combination with another lyoprotectant. They exert various interactions with the protein to stabilize it, such as hydrogen bonding, hydrophobic interactions, electrostatic interactions, and osmoprotection. Conclusions: This review concludes that disaccharides are the most effective lyoprotectants, while other groups of lyoprotectants are best used in combination with other lyoprotectants.