As many medications are administered jointly, they often give larger benefits, counteract disadvantages, and enhance treatment results compared to monotherapy. Whether natural or synthetic, injectable biomaterials can form degradable networks in situ, decreasing patient pain and cost while presenting new and promising possibilities for minimally invasive surgery. Biomaterials' ability to create and manufacture injectable systems is strongly impacted by their physicochemical and mechanical properties. The design and manufacture of injectable systems containing cells, therapeutic molecules, particles, and biomolecules that can be injected into geometrically complex body tissue regions poses a significant challenge as they must ensure drug/biomolecule/material bioactivity, cell survival and retention. Hydrogels are a promising choice in this case given their amazing ability to manipulate, encapsulate and co-deliver pharmaceutical chemicals, cells, biomolecules, and nanomaterials. Hydrogels can alter their mechanical and deteriorating qualities by adjusting the cross-linking technique and chemical composition. The ability to modify IH's mechanical strength permits co-encapsulation of medicinal compounds, cells, nanomaterials, and growth factors in the matrix in situ, allowing for multimodal synergistic therapies.To boost the prospects of translating IHs into normal clinics, various barriers and outstanding scientific issues must be tackled in the future. Future investigations, including the application of IHs in multimodal synergistic treatment, should start with large animal models such as monkeys and dogs or even ex vivo human tissue models. In addition, the period of in vivo evaluations should be prolonged from weeks to months for trustworthy and accurate data to be translated to clinical trials. On the one hand, the toxicity of certain crosslinking agents used in IH synthesis must be considered, as the residues will cause unwanted in vivo reactions.Toxic crosslinkers, on the other hand, may interact with therapeutic molecules/biomolecules or nanomaterials trapped in the hydrogel matrix, causing loss of bioactivity. Similarly, IHs' sol–gel transition is a vital issue requiring much investigation. A quick sol–gel transition of precursor solutions might cause the fluid to be caught in the needle, whereas high-viscosity precursor solutions need high injection force, resulting in physician hand fatigue and patient annoyance. Other concerns for clinical IH translation include fast release and rate of degradation. Degradation rate is critical in controlling therapeutic drug release and tissue regeneration. Fast hydrogel breakdown may trigger early inflammatory reaction due to breakdown products, whereas delayed degradation may result in insufficient release of therapeutic drugs. Changing the composition, structure, and crystallinity of polymers must be employed to customize the breakdown rate. Expert researchers will be better equipped to tackle these challenges if they have a deeper knowledge of polymers' physiochemical features. Overall, future IH design should focus on building simple, well-defined 3D networks with low toxicity, high biodegradation rate, and acceptable functionality.
Thermo-Responsive Hydrogels: From Recent Progress to Biomedical Applications
