**6.3 Clinical uses in dentistry**

*Alginates - Recent Uses of This Natural Polymer*

**Porcine islet types used**

Sertoli cells encapsulated in scaffold

12 Neonatal +

7 Encapsulated neonatal

1 Encapsulated fetal

14 Encapsulated

8 Encapsulated

pre-weaned

*make up the graft which are implanted during transplantation.*

pre-weaned

**Number of islets transplanted/ kg of body weight**

**Transplantation** 

subcutaneous space

**Study outcome Reference**

[124, 125]

[154]

[127]

[127]

[123]

• Deceased exogenous insulin requirement for up to 4 years (50%) • No serum C-peptide detected

• Two patients achieve independence for 32 weeks • 6 Patients demonstrate lower HBA1c

• -12-week period of 30% reduction in insulin requirement • Improvement in glycemic control for 14 weeks • Detectable C-peptide for 11 months • Live Islet detected for 9.5 years

• Moderate decrease in insulin requirement in 57% of patients • Major reduction in hypoglycemic episodes

Patients that received 20,000/kg maintain 7% HbA1c for 600 days. Reduced Hypoglycemic events

**site**

14,000–21,000 Scaffold in

5000–1000 Intraperitoneal space

15,000 Intraperitoneal space

5000–20,000 Intraperitoneal space

5000–20,000 Intraperitoneal space

*Selected clinical encapsulated islet xenotransplantations in humans. IE is used to denote islet equivalents that* 

**Number of subjects (n)**

**48**

**Table 1.**

The hydrophilic nature of alginate along with hydrogel forming and biocompatible nature has made it a staple hydrocolloid for application in the field of dentistry [137]. Alginate-based gels have traditionally been used in dentistry to provide the dentist with impressions of teeth and bitemarks which can then be used as a template for dental implants [138–140]. Alginate is frequently used in clinical trials to obtain impressions when comparing various dental procedures [141–144]. In a recent clinical trial, silicone was found to be favored among patients in terms of comfortability although alginate impressions were found to be a cheaper procedure option [145, 146]. Alginate-containing matrices have also been tested for advanced periodontitis treatment, when compared to the normal 0.2% chlorhexidine treatment alginate-containing Emdogain® saw significant reduction in plaque viability [147]. These alginate-containing enamel matrices have also shown significant clinical regenerative capabilities for periodontal disease symptoms such as intrabony defects and gingival recession [148, 149].

## **7. Future direction for alginate-based biotechnologies**

The development and use of alginate macro/micro devices for implantation have met both improvements and challenges. Specifically, alginate has been used in the production of microcapsules as well as scaffolds as a way to implant encapsulated islet cells in *vivo*. The use of natural polymers such as alginate introduces immunogenic and foreign body responses, which impact the functionality of the device over time [150]. For example, the mechanical integrity or structure of the device could be compromised, or it can decompose while inside the recipient. As a potential solution, alginate can be chemically modified so its properties can be better controlled against inflammatory response and mechanical stress [151]. This chemical modification includes both ionic and covalent crosslinks within alginate polymers which will increase the mechanical stability of both scaffolds and microcapsules [151]. This method of using two types of crosslinking to create the microbeads compared to using only covalent crosslinking has shown results of greater stability of these microcapsules within cells after weeks following implantation [151]. Furthermore, in the long run, purification techniques of alginate hydrogels can be improved to decrease PAMP concentration which would help reduce FBR [92]. Purifying alginate gels of PAMPs can be difficult for those with a high G content, which are stronger and more viscous. However, the use of chemical extraction or dialysis methods as well as specific purification methods would be required to remove these molecules. Another potential

solution to overcome graft failure is to use smaller islet cell graft volumes with vascularized membranes to produce stable neovascularization near the grafted tissue [152]. Using a macroencapsulation device such as TheraCyte and loading it with islet cells of smaller volume can increase blood supply near the site of encapsulation [152].

Given the molecular composition of alginate and its ability to crosslink and form hydrogels, this biomaterial can be used in an array of medical and clinical applications. Unfortunately, the implantation of alginate induces an immune response of the host, producing setbacks that current labs are attempting to solve. Because of both macrophages mediated and T-cell mediated immune response, the alginate macro/micro device loses its viability and long-term function once it is implanted in the host. Strategies aiming to reduce or prevent fibrosis on alginate encapsulated cells present conflicting results. Newly developed capsules contain alginate without a polycation layer shown improvement potential because the pro-inflammatory characteristic of polycations have been connected to fibrotic growth around capsules [153]. For alginate beads, removing the polycation layer can lead to less stability and more permeability to cytokines and growth factors [153].

Currently, the main focus regarding implantable alginate hydrogels is to address problems such as immune response, adequate sources of oxygen, and fibrosis. As more alginate-based devices are being brought into clinical application, these strategies among others should be considered and pursued for current and future alginate-based device production.
