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Cell-Free Amniotic Membrane-derived Hydrogel Boosts Skin Wound Healing

Review of “Solubilized Amnion Membrane Hyaluronic Acid Hydrogel Accelerates Full-Thickness Wound Healing” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Treatment strategies for full-thickness skin injuries currently suffer from a number of setbacks that have prompted the search for an efficient bioactive agent that does not require a cellular component. A recent study from the laboratory of Anthony Atala (Wake Forest School of Medicine, North Carolina, USA) demonstrated that a hyaluronic acid (HA) hydrogel [1] containing amniotic fluid stem cells (AFSCs) improved wound healing via the release of paracrine acting factors, even given the transient nature of the cell component [2]. 

The team now returns with a new STEM CELLS Translational Medicine article in which they describe the development of an easy to store and apply cell-free hydrogel containing solubilized amniotic membrane [3] that accelerates wound closure and re-epithelialization [4].

To create the easy to store and apply cell-free hydrogel, known as HA-SAM, Murphy et al. first solubilized the amniotic membrane (SAM) by freezing, pulverizing, and degrading donated tissues before combining with HA. Of note, this process does not remove cells from the amniotic membrane, but in fact keeps all cellular and extracellular components, albeit in a solubilized form. Subsequent protein release analysis demonstrated that HA-SAM slowly releases growth factors known to promote keratinocyte proliferation (bFGF, NGF, HB-EGF), keratinocyte migration (HGF, IGF1, EGF, FGF-7), and neovascularization (FGF-family, EGF-R, EG-VEGF, VEGF) over a period of seven days.

Employing a mouse full-thickness skin wound model, the study highlighted both the easy to apply nature and the wound healing efficacy of HA-SAM. HA-SAM-treated wounds initially closed quicker and resisted contraction, and subsequently, treated wounds presented with thicker regenerated skin, an increased number of blood vessels, and higher numbers of proliferating epidermal keratinocytes than untreated mice or those treated with an HA-gel only (See Figure).

Even given their undoubted success of their cell-free approach, the authors point to the need for studies in large-animal and disease models and the possible assessments of three-dimensional bioprinting approaches to delivery, hydrogel stiffness, and matching protein/growth factor release kinetics to specific wound types. 

Exciting news with the promise of more breakthroughs, keep up to date with all the new advances here at the Stem Cells Portal!

Discussion Points

  • Will this strategy work well in other wounds types?
  • Will large animal trials demonstrate the utility of this therapeutic option?
  • Are there other tissues/cells other than the amniotic membrane that may prove useful in a similar manner?


  1. Murphy SV, Skardal A, and Atala A, Evaluation of hydrogels for bio-printing applications. J Biomed Mater Res A 2013;101:272-84.
  2. Skardal A, Murphy SV, Crowell K, et al., A tunable hydrogel system for long-term release of cell-secreted cytokines and bioprinted in situ wound cell delivery. J Biomed Mater Res B Appl Biomater 2017;105:1986-2000.
  3. John T, Human amniotic membrane transplantation: past, present, and future. Ophthalmol Clin North Am 2003;16:43-65, vi.
  4. Murphy SV, Skardal A, Song L, et al., Solubilized Amnion Membrane Hyaluronic Acid Hydrogel Accelerates Full-Thickness Wound Healing. STEM CELLS Translational Medicine 2017;6:2020-2032.