# The Impact of Optogenetics on Regenerative Medicine
## 3 Biomedical Applications of Optogenetics
### Clinical and Tissue Engineering and Regenerative Medicine (TERM) Applications  
Optogenetic applications can be related to emerging biomaterials and photoelectric technologies. One of the strategies used to overcome the barriers to human tissue is to transform energy from near infra-red (NIR), X-rays, and ultrasounds into visible light. NIR light is highly promising since lipids, hemoglobin, and water have an absorption coefficient of 650-900 nm, which is lower than such tissues investigated by NIR [49]. [PERSON] et al. [49] demonstrated that optogenetics could stimulate deep-brain neurons. Some neurological applications have taken advantage of the use of lanthanide-doped nanoparticles (UCNP): UCNPs are able to convert the low-energy photons into energy. The optogenetic activation with UCNPs only requires a host material (sodium fluoride ittria--NaYF4) able to ensure a proper photonic absorption (Yb3+) [50]. Unfortunately, several tissues located in the deepest zone cannot be investigated for clinical purposes. For this reason, researchers are studying alternative solutions, such as X-optogenetics, which involves X-rays, and U-optogenetics, which exploits sonoluminescence [51, 52]. It is well known that ultrasonographic waves and X-rays penetrate deeper into human tissues than NIRs. Although promising, these applications must be carefully evaluated for clinical applications and preclinical safety [53]. The inorganic light-emitting diodes (\(\upmu\)-ILED) are able to provide support during minimally-invasive in vivo treatments. The idea is to apply \(\upmu\)-ILEDs in multi-function systems, with mechanical, thermal, and electrophysiological sensors to obtain accurate feedback in complex clinical evaluations [54]. [PERSON] et al. [55] designed a modern example of closed-system technology in 2019, made from \(\upmu\)-ILED, combining optogenetic neuromodulation with optoelectronic technology, to control pathological conditions [55]. [PERSON] et al. [56] have proposed a non-invasive technique based on ultrasounds and optogenetics. Through the application of ultrasounds, the blood-brain barrier (BBB) has been overcome, favoring the non-invasive introduction of channelrhodopsins and their related activation with a light-based activation. The approaches with photostimulation are preferred to those involving the emission of radiation or electrical impulses because of the low invasiveness and the lower possibility to induce side effects. Advances in tissue engineering and regenerative medicine (TERM) have shed light on important scenarios in medicine, with a specific interest in tissue repairing. Optogenetics is pretty useful in the study of mechanisms supporting cell development and regeneration, in order to better understand the physiological processes of tissues and organs replacement [57]. Moreover, optogenetics can monitor the dynamic signaling related to several cellular processes: this is very important to support the future 3D bioprinting techniques that will be aimed to exactly replace cells, growth factors and biomaterials in the conditions able to create tissue-like or organ-like parts of the human body [58]. Furthermore, the optogenetics approach, used with specific target genes, allows monitoring the cellular processes involved in the pathogenesis of some morphological anomalies or even some tumors [59]. The proper combination of photoreceptor and gene engineered effectors has widely improved the fields of application of optogenetics. Generally, this strategy requires guidance modules (GMs) [60], light-sensing modules (LMs), and effector modules (EMs). More in detail, GMs will find the proper target genes; LMs will determine the spectrum of light-based activation and kinetics of transcription [61]; EMs will be involved in different functions, such as gene activation and recombination, and epigenetic modification [62]. Optogenetic stimulation has been found to improve both bradykinesia and hypokinesia that characterize the clinical picture of patients with [PERSON]'s disease [63].