**4. Clinical applications**

The novel approach to use nanomaterials in regenerative medicine has established the design of functional tools to simulate, diagnose and stimulate cell growth of tissue or organs [16].

Burn wounds are a critical issue due to the widespread deaths due to the constant bacterial resistance to conventional antibiotics. In this regard, novel nanomaterials such as topic antimicrobial systems have been obtained to produce combined antibacterial/tissue regeneration responses in thermal burns. Luna-Hernández et al. [68] report the use of nanocomposites based on CTS/AgNPs synthesized by *in situ* chemical reduction method, obtaining embedded spherical AgNPs around 7 nm, as presented in **Figure 3**.

In this research, controlled thermal burns produced in rats were treated with nanocomposites with different NPs concentration deposited at wound areas. These results showed the combined antibacterial responses to *S. aureus* and *P. aeruginosa*, depending on NPs concentration and the mesh formation of hydrated chitosan, which allowed bacterial penetration. As a result, significant tissue regeneration was shown in the thermal burns treated with CTS/AgNPs nanocomposites in comparison with untreated one, as presented in **Figure 4**. Also, histological assays showed important tissue regeneration responses in contact with nanocomposites, suggesting the myofibroblasts regeneration and accelerated healing processes compared to uncovered thermal burns.

Chemotherapy and radiation exert their effects by inhibiting tumor cell growth and by blocking tumor reformation. However, some cancer patients present tumor relapse due to cancer

**Figure 3.** AgNPs synthesized by *in situ* chemical reduction in CTS matrix.

**Figure 2.** Fibers of CTS with AuNPs and AgNP on the surface of the polymer.

list of contributions elsewhere [67].

34 Tissue Regeneration

nanomaterials formulated by AgNPs/CTS and AuNPs/CTS-GMA.

Is clear that there are more possibilities for NPs and natural polymers, here we have offered a slight landscape of that, additionally to Au and Ag different metals such as copper (Cu) also could be used in biomedical applications, but the noble metals are a field with an extensive

**Figure 1.** UV-vis absorption spectra of silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), and their corresponding

penetration. Authors claimed that graphene oxide could act as a light activable switch to trig-

Trends in Tissue Regeneration: Bio-Nanomaterials http://dx.doi.org/10.5772/intechopen.75401 37

In the present chapter, the use of biopolymers-based nanostructures is addressed, including biomaterials and stem cells, bio-nanocomposites, and specific clinical cases where these systems were employed. We addressed the current challenges in the formulation of functional materials based on biopolymers/metal NPs to mimic the cellular behavior of living organisms. It is important to note that material functionality must be improved to synergistic properties, for example, combined antibacterial/tissue regeneration responses, aiming to contribute the specific cell regeneration and avoiding the bacterial colonization. In this sense, the recent trend in nanomaterials development must be focused in the design of functional systems which combine their physic-chemical and biological characteristics, aiming to produce efficient cellular growth and contribute to tissue engineering approaches. We emphasize the future challenges and perspectives in the design of biocompatible and nontoxic nanocomposites with high efficiency as a promoter for tissue regeneration and many other biomedical applications.

The authors would like to thank CONACYT for the financial support through CB-2016- 2101/286926 and Problemas Nacionales 2016-2101-2397 projects. They would also like to thank MC. Reina Aracely Mauricio-Sánchez for their technical support in chitosan experiments and MC. Lourdes Palma Tirado for their technical support in TEM imaging. Thanks to Dr. Lucero Granados-López and Dr. Rodrigo Muñoz-Acosta for their histochemical and

pathology contributions in thermal burns treated with bio-nanocomposites.

The authors declare no conflict of interest, financial or otherwise.

ger drug release from liposomes upon NIR irradiation.

**5. Conclusions**

**Acknowledgements**

**Conflict of interest**

**Abbreviations**

Ag Silver

Au Gold

CTS Chitosan

AgNPs Silver nanoparticles

**Figure 4.** Photographs of controlled thermal burns untreated and treated with CTS/AgNPs nanocomposites.

stem cells, which cannot be killed by these therapies. These cancer stem cells are able to form new colonies and regenerate tumors. It is of great importance to develop new therapeutic approaches to selectively target stem cells. There are novel therapies using NPs to target stem cell-specific markers or signaling pathways [69]. In other hand, glioblastoma multiforme tumors show resistance to radiotherapy and chemotherapy and this is believed to happen due to tumor stem cells. NPs carrying antitumor drugs have to be able to reach the tumor cell, by crossing a series of membranes slide across the blood-brain barrier. For NPs to reach the tumor in a specific way, some strategies have been incorporated like the use of antibodies or peptide molecules which recognize tumor cells antigens to improve the therapeutic efficacy by means of increasing tumor cell uptake and accumulation into the cytoplasm [70].

In other hand, Gilbert and Osterhout suggested the use of NPs from the delivery of chondroitinase ABC in rats, a therapeutic enzyme to treat spinal cord injury in order to cause axon regenerative responses. In this case, the released enzyme from NPs produced digestion of chondroitin sulfate proteoglycans, which are the lesion markers [71]. For spinal cord injuries, it has been reported the use of biocompatible polymer NPs based on poly(lactic-co-glycolic) encapsulated methylprednisolone, which can reduce the possible neurological deficits after spinal cord procedures, considering ultralow drug doses at local delivery [72]. Another route to treat spinal cord disease is by using cerium oxide NPs. In this regard, Das et al. report the anti-oxidant, photocatalytic and biocompatibility behavior of nanomolar concentration of NPs, acting as neuroprotectors without cytotoxic effects [73].

Cancer therapy is a major challenge in order to design alternatives for detection and treatment. In particular, the use of aptasensors is emerging as a novel strategy for cancer detection. Aptasensors described as recognition elements derived from artificial fragments of DNA or RNA, easily synthesized and modified to target as biomarkers, with low immunogenicity and high affinity. In this regard, graphene nanocomposites decorated with metallic NPs obtained from Layer by Layer deposition have been considered a novel tool for specific polypeptides detection [74].

For drug delivery systems, Sahu et al. [75] proposed the use of graphene nanosheets integrated into liposomes as drug delivery vehicles, monitored by NIR light. Some advantages of using NIR light to liposomes detection are their non-toxicity, specificity, and high tissue penetration. Authors claimed that graphene oxide could act as a light activable switch to trigger drug release from liposomes upon NIR irradiation.
