HealDot: Subcutaneous Hydrogel to Enable Non-Scarring Regenerative Healing

Lead investigator: Ellen Heber-Katz, PhD

Unmet need

Tissue loss or injury due to trauma or degenerative processes present an arena of enormous clinical need unaddressed by medical or surgical science. While considerable effort has been devoted to developing stem cell therapies to address these needs, broadly effective medicines to restore normal tissues and their functions after trauma or degeneration have remained elusive.

Basic research studying the regenerative capabilities of amphibians and the MRL mouse strain that can regenerate lost appendages, where scars do not develop at the injury site as a result of epimorphic healing, have now led to the development of a novel medicinal agent that mimics these unique capabilities. This agent — informally referred to as a HealDot due to its delivery as a subcutaneous hydrogel injection — offers an off-the-shelf modality to reprogram inflammatory and indigenous stem cell capabilities needed for non-scarring regenerative healing in mammals.


HealDot is a proprietary supramolecular polymer composed of a hydrogel-delivery component that is conjugated to a pro-drug component. This polymer conjugate is injected subcutaneously at a site remote to the site of tissue injury or degeneration. From this depot, the active drug is released from the hydrogel continuously over a 7- to 10-day period, after which the hydrogel depot is dissolved. Injections of this type offer the opportunity to tailor time-release regimen of drug administration to clinical needs. The regimen does not interfere with standard-of-care clinical protocols for tissue healing in various settings, since the polymer conjugate is delivered distal to the site of tissue injury/degeneration.

In utilizing a supramolecular design, HealDot offers an off-the-shelf modality that captures a latent capability in patients for epimorphic healing, a process suppressed in mammals after fetal development but not in adult amphibians. Accordingly, this technology restores an inherent capability that bypasses any need for exogenous stem cells in stimulating tissue regeneration, avoiding implantation of a foreign material directly into the injury site.

Unique attributes

First, unlike stem cell approaches, this technology is comprised of a small-molecule–based medicine.

Second, this technology constitutes an off-the-shelf modality, the synthesis and storage of which is less complex and less expensive that stem cell approaches. Preclinical investigations conducted to date illustrate efficacy in models of cartilage healing, lethal liver resection and jawbone degeneration. Accordingly, HealDot may have utility in many different tissue types to promote regenerative healing by unleashing a latent capability in mammals that is present during fetal development but lost in adults.

Lastly, pilot studies suggest that HealDot can exert anti-aging effects, possibly based in restoring tissues damaged by natural aging processes.

Clinical applications

HealDot drug-hydrogel conjugates deposited under the skin by subdermal injection offer a novel treatment modality for non-scarring healing of tissue wounds caused by trauma or natural or pathogenic degenerative processes. In principle, this invention enables a general medicinal strategy to program indigenous stem cell-dependent processes of regenerative healing that avoids fibrotic deposition (scar tissue formation). Accordingly, development in many clinical settings of tissue trauma or degeneration, including those characterized by orphan status, could be conceived as a pathway toward clinical proof of concept.

Stage of development

Preclinical genetic and therapeutic proof of concept in mice has been published for a first-generation drug-hydrogel formulation. The current stage of work focuses on a second-generation drug-hydrogel conjugate thought to represent a potential clinical lead agent.

Intellectual property

  1. Novel drug-hydrogel conjugates and their uses for epimorphic tissue regeneration. Pending patent application filed with University of California at Berkeley.
  2. Epimorphic tissue regeneration and related hydrogel delivery systems. U.S. Patent No. 10,307,415 (issued 4 June 2019) and U.S. Patent No. 9,675,607 (issued 13 June 2017) are each co-assigned to The Wistar Institute and Northwestern University where Dr. Heber-Katz and her co-inventor (now at University of California at Berkeley) had worked previously.

Collaboration opportunity

LIMR seeks partners to advance IND-enabling studies of the subdermal HealDot drug-hydrogel as unique modality for regenerative healing.

References and Publications

  1. Zhang Y, Strehin I, Bedelbaeva K, Gourevitch D, Clark L, Leferovich J, Messersmith PB and Heber-Katz E. Drug-induced regeneration in adult mice. Sci Transl Med 2015:7;290ra92.
  2. Cheng J, Amin D, Latona J, Heber-Katz E and Messerschmidt PB. Supramolecular polymer hydrogels for drug-induced tissue regeneration. ACS Nano 2019;13:5493-5.
  3. Nagai K, Ideguchi H, Kajikawa T, Li X, Chavakis T, Cheng J, Messersmith PB, Heber-Katz E, Hajishengallis G. An injectable hydrogel-formulated inhibitor of prolyl-4-hydroxylase promotes T regulatory cell recruitment and enhances alveolar bone regeneration during resolution of experimental periodontitis. FASEB J. 2020 Aug 19. doi: 10.1096/fj.202001248R.


Institutional contact: George C. Prendergast, PhD, LIMR President and CEO, 484.476.8475, [email protected]

L2C Partners contact: Merle Gilmore, 610.662.0940, [email protected]