Hyaluronic Acid Hydrogel: The Future Key to Tissue Repair and Regeneration

Alexandra G. Brist

Dr. Robert Morrison

NEUR 300-001

15 December, 2021

Hyaluronic Acid Hydrogel: The Future Key to Tissue Repair and Regeneration

“The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord,” a research paper penned by Li et al., focused on “an injectable nanofiber-hydrogel composite” that was investigated to learn whether it is capable of strengthening and potentially healing an “injury to the spinal cord [that] causes long-lasting loss of nervous tissue” (Li et al., 2020). Hyaluronic acid (HA) hydrogel, which was the hydrogel of focus in this study, was used in the place of a contused spinal cord segment by replacing the lumen of the injury that had previously collapsed. The damaged tissue either caused pain or a loss of feeling and functionality in the participants of the study. It was noted that HA hydrogel was utilized in this study because it is especially compatible with the spinal cord and surrounding tissue and is “naturally distributed throughout the central nervous system” (Li et al., 2020). 

This study in particular included the study of HA hydrogel in rats and it was noted early on that “none of the rats required treatment for pain or distress” (Li et al., 2020). It is clear that the researchers were keeping in mind the wellbeing of the animals and holding high ethical standards. Compared to control groups, the researchers revealed that the HA hydrogel succeeded in bettering the innervation within damaged spinal cord segments. Specifically, the researchers explained that improvements were seen “28 days after treatment” and any contused spinal cord segments that were studied had a “higher immature neuron presence” and were noticeably wider, larger, and denser. (Li et al., 2020). 

Some questions to be asked about this procedure, in general, revolve around the costs related to this new science and how safe it is expected to be for patients, especially in the long term. What will the out-of-pocket cost look like for patients, and how much will insurance cover? Will it be accessible to all patients that suffer from spinal cord or nearby tissue injuries? How might this procedure and potential risks change with human patients compared to this study that utilizes rats? With the ability to degrade easily, how long will the HA hydrogel last and improve loss of feeling or pain in these injuries? Will patients need to undergo routine procedures to maintain improved pain levels and feeling in these segments? Were any adverse or allergic reactions recorded in this experiment? How might the reactions differ in humans compared to rats?

It has been recorded that adverse reactions do occur in some patients that are given IV contrast injections including elements like iodine, a naturally-occurring halogen needed to make proper thyroid hormones and regulate the body’s metabolism. Iodine, like hyaluronic acid, is found in the body naturally. Patients that are unable to tolerate IV contrast are given substitutes if they need a CT scan or MRI. Should an adverse reaction occur with HA hydrogel, is there an alternative measure that can be taken or another hydrogel that has been closely studied enough that may be used in place of HA? Are patch tests and other allergy exams run before inserting HA hydrogel in the damaged sections of spinal cords and tissues of patients? If not, they should certainly be done so as not to cause extra complications throughout the procedure. The NIH reports research from Italy that states “delayed immune mediated adverse effects to hyaluronic acid” are not uncommon and can produce other “non-allergic, local side effects” like “slight edema, ecchymoses, hypercorrection, and bluish discoloration” and “other more serious long terms symptoms” like “tender granulomas, edema, and indurated nodules…suggesting an allergic mechanism” (Bitterman-Deutsch, 2015). As HA hydrogel continues to be used in various new procedures like bone and cartilage tissue engineering, maintaining robust procedures for keeping patients safe will be integral to the success of this work. 

In “The Application of Hyaluronic Acid-Based Hydrogels in Bone and Cartilage Tissue Engineering” authored by Li. et al. (a different Li than the original paper), a research team from China discusses the advantages and disadvantages of HA hydrogel usage and recent applications in medicine, specifically in the Department of Orthopedic Surgery in Changchun, China. The researchers reflect that overall, hyaluronic acid hydrogels “have many advantages, such as promoting cell adhesion and proliferation and wound healing” and “they also demonstrate sufficient biological activity for stimulating a microenvironment for cell survival” (Li. et al., 2019).  However, the disadvantages of using HA hydrogel include the requirement of “...further modification and…a poor degradation rate and insufficient mechanical performance” (Li et al., 2019). These disadvantages connect with the earlier notion that it may be worthwhile to experiment with other hydrogels that can be used in the place of HA that may require less alteration to be used in these experiments.

A major application of these HA-based hydrogels is that they can be used to help treat injuries due to cartilage tissue engineering (CTE) and bone tissue engineering (BTE) (Li et al., 2019). Due to disadvantages such as a “hydrophilic nature and lack of mechanical integrity, HA requires chemical modification and cross-linking to alter it for use in BTE and CTE applications”, potentially leading to greater costs for the procedure, extended preparatory time, and overconsumption of resources (Li et al., 2019). Despite these issues, HA hydrogel is preferred in these procedures because it allows for the most extensive, efficient “cell migration and proliferation” (Li et al., 2019). It is clear that the future holds a lot of promise for HA hydrogel in helping patients gain back feeling and lessen pain in contused spinal cord segments and injured tissues.

References 

Bitterman-Deutsch, O., Kogan, L., & Nasser, F. (2015, March 30). Delayed immune mediated adverse effects to hyaluronic acid fillers: Report of five cases and review of the literature. Dermatology reports. Retrieved December 16, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387334/.

Li, H. et al., (2019, December 20). The Application of Hyaluronic Acid-Based Hydrogels in Bone and Cartilage Tissue Engineering. Retrieved December 10, 2021, from https://www.hindawi.com/journals/amse/2019/3027303/.

Li, X. et al., (2020, March 16). The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord. Retrieved December 10, 2021, from https://www.sciencedirect.com/science/article/pii/S0142961220302246?via=ihub.