Regenerative medicine using autologous stem cells is showing potential in accelerating healing for a number of conditions. These authors explore the future of regenerative medicine in burns, particularly in patients with diabetes.
At the intersection of increasing healthcare costs, an aging population, recognition of difﬁcult-to-treat infection threats, and the rise in diabetes and obesity worldwide, the treatment of wounds and burns associated with patients with diabetes has become a significant challenge.
A recent retrospective analysis of Medicare beneﬁciaries identiﬁed that 8.2 million people had wounds with or without infections, with costs for acute and chronic wound treatments ranging from $28.1 billion to $96.8 billion.1 The highest expenses were for surgical wounds followed by diabetic foot ulcers (DFUs), with a higher trend toward costs associated with outpatient wound care compared with inpatient. With the alarming emergence of antibiotic drug-resistant pathogens and ineffective care of diabetic foot ulcers, incidences of sepsis and leg amputations, respectively, continue to rise precipitously.
But at this moment in time, regenerative medicine—a promising field of medicine that harnesses the body’s innate abilities to heal and defend—is a treatment approach with the potential to restore tissue, perhaps equaling or exceeding pre-trauma levels. This is good news for burn center and healthcare professionals, who can look forward to delivering improved patient outcomes and quality of life at lower overall costs.
A Snapshot of the Challenges
Diabetes mellitus affects 463 million adults globally with an increase to 700 million expected by 2045.2 Diabetes is the leading cause of non-traumatic lower extremity amputations in the United States. A DFU, a major complication of diabetes, is a full thickness wound located below the ankle in patients with diabetes and is associated with diabetic neuropathy and peripheral arterial damage. DFUs occur in 15% of patients with diabetes at an annual healthcare cost of $9 billion in the U.S.3 Approximately 14-24% of these DFU patients will require limb amputation.
Patients with diabetes comprise a significant population seen in burn centers, with most of these burns resulting from contact with hot objects or scalds. The American Diabetes Association lists the hazards of treating diabetic feet with hot water bottles, heating pads and hot water soaks.4 Patients with diabetes are also known to experience more infections in clean wounds than patients without diabetes, and also heal slower, especially in the extremities.
What’s more, people with diabetes experience longer hospitalizations and increased morbidity, regardless of the quality of the patient’s anti-diabetes therapy prior to injury, and diabetes in burn patients is associated with an increased risk of total morbidity.5
Currently, burn patients with diabetes comprise 6% of the adult population and 32% of the senior population.4 Because this population is on target to become a large percent of burn center and hospital admissions in the years ahead, they will require special attention.
Chronic wounds such as venous, diabetic and pressure ulcers are difficult to heal and cause considerable suffering. Complications include infection, amputation and even death.6 Advanced therapies help a portion of patients, but significant percentages remain unhealed after treatment, and even more patients are at risk for recurrence and continued morbidity due to underlying pathophysiology.
What Chronic Wounds Cost
Conservative estimates for total Medicare annual spending for all wound types ranged from $28.1 billion to $31.7 billion.1 Among Medicare recipients, diabetic ulcers cost $18,000 per patient per year.7 As the population ages and the absolute number of chronic wounds increases, these costs will likely become unsustainable.
Important contributors to chronic wound costs include outpatient/physician office visits, emergency department visits, hospitalizations, and, for diabetic foot ulcers, amputations.6 Expensive complications, such as infection, only occur if wounds are open. Any kind of treatment that heals a high proportion of wounds quickly, completely and sustainably, like regenerative medicine using autologous stem cells, has the potential to significantly improve outcomes, reduce expenses and enhance quality of life.
Reaching this goal will require not only compelling efficacy and safety data, but also comparative effectiveness, health economic and population health analyses to demonstrate the impact of innovative approaches for patients, burn centers and healthcare systems.6 This is where regenerative medicine comes in.
How Regenerative Medicine Can Help Burn Patients
Regenerative medicine is a branch of translational research in tissue engineering, cell biology, and molecular biology that encompasses the process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function. It has been shown to accelerate healing in a clinically relevant way and restore the structure and function of damaged tissues and organs.6 Cosmetic restoration may also be afforded by regenerative medicine for many conditions (e.g., burn wounds, diabetic foot ulcers, breast reconstruction, etc.).
This could give clinicians and administrators of outpatient wound clinics an effective approach to treat acute and chronic wounds. The goal is to find a way to restore the structure, function, and cosmesis of tissues and organs that have undergone trauma, surgery, or disease, such as body disfigurement from accidents and cancer with the hope of replacing allogeneic organ transplantation with strategic self-cell replacement using autologous stem cells.
Regenerative medicine holds the promise of improving quality of life for patients worldwide, with scientists utilizing powerful technology to create new body parts from a patient’s own cells and tissues and eliminating tissue rejection.
The field consists of four key areas: Medical devices and artificial organs; tissue engineering and biomaterials; cellular therapies; and clinical translation—“research that leads to better understanding of disease, and/or development of new diagnostic tests or treatments,” according to the Walter + Eliza Hall Institute of Medical Research.8
Regenerative medicine is a logical approach to wound healing because of the accessibility, abundance, and types of stem cells in skin and adipose tissues, the lack of success using bone marrow-derived stem cells, the regenerative nature of healing, absence of good limb salvage treatments and the current application of cell therapies. As a result, additional basic and applied research is badly needed to inform regenerative strategies and usher in the development of innovative and viable methods and therapeutic products.
Regenerative medicine using autologous stem cells has the potential to effectively treat acute and chronic wounds associated with burns and diabetes; heal wounds faster and more completely without further tissue grafting or surgeries; and prevent serious complications, such as infection and amputation.
How Regeneration Works
In wound healing, repair leads to a nonfunctional scar, while regeneration leads to tissue that is similar to its original form, function, and appearance, basically restoring missing tissue.9
Regenerative medicine may include tissue repair and/or enhancement, the development of “new” tissue and techniques, such as stem cell therapies, molecular medicines, genetic manipulations, organ- and tissue-engineered constructs, and nanotechnology.6
As a multidisciplinary field, regenerative medicine incorporates surgery, dermatology, organ transplantation, biomaterials science, bioengineering, developmental biology, and stem cell biology, with a scope that includes technologies that induce the body to redevelop missing tissue and engineer tissue or organs that replace missing structures.
Why Collaboration Is the Key to Scientific Advances
Further scientific discovery and product/process development that lead to improved clinical outcomes will require not only investment, but also consensus and collaboration among leading organizations across every area of regenerative medicine.
For example, regenerative technologies developed in one therapeutic area could be applicable in other areas to uncover the full range of regenerative medicine benefits. Currently, research collaborations are focusing on much-needed research in regenerative medicine and chronic diseases to revolutionize methods for reducing complications from burn wounds and diabetic foot ulcers across large populations.
Such collaborations hold great potential for fostering breakthroughs in biomedical technologies. Consider the scenario of an automated, closed medical device isolating stem cells from autologous tissues used in conjunction with a medical device that sprays these cells onto a wound gently as single cells. The process lasts 90 minutes from tissue isolation to completion of cell spraying. Such a scenario is becoming a reality and may present a special opportunity for investigations and applications in a wide range of regenerative therapies to improve the quality, efficiency and effectiveness of patient care by not only engendering new treatment methods, but also by making thoughtful and systematic changes to healthcare and health systems.
Pressure Grows for Research Support
A campaign to adapt new strategies based upon sound scientific evidence should support the continuation of scientific and medical work, providing needed infrastructure—such as lab certification, advanced technology and equipment, clinical and administrative staff to support research initiatives, and start-up funding for biotech companies to pursue product development and commercialization.
Following the awarding of the Nobel Prize to Shinya Yamanaka in 2012 for his pioneering work in adult stem cell biology, the Japanese government undertook an ambitious program and promoted the rapid advancement and translation of basic and applied research in regenerative medicine to medical treatments with the Regenerative Medicine Promotion Act of 2014, regulatory allowances, and funding programs.10 This led to the availability of many new commercially viable stem cell therapies for many clinical diseases and conditions in Japan.
Here in the United States, regenerative strategies have the potential to transform our approach to disease, and how wounds are treated in burn centers and hospitals. To reach this goal, developments toward regenerative medicine in wound healing must be explored more fully to identity the challenges and opportunities facing this emerging field and to prepare and incorporate new advances.
Key challenges include the basic understanding of which cell type and tissue source of stem cells work best to heal or restore damaged tissues and organs. What’s more, the regulatory pathway for approval of regenerative medicines needs to keep pace with basic and applied stem cell discoveries. Finally, the reimbursement of medical costs associated with regenerative medicine treatments by governments and third-party payers must be clarified and in step with the oncoming wave of regenerative medicine regulatory approvals.
Such high-level initiatives require greater federal funding, philanthropic donations and academic-industry partnerships to aid in the significant advances in regenerative medicine. Research collaborations in this area represent the first phase toward developing meaningful and quality therapeutic treatments that will benefit patients in the United States and around the globe.
Bill Oldham is the Founder and Chairman of the Board of the Thought Leadership & Innovation Foundation (TLI).
Robin Robinson is a Fellow of TLI and the Vice President–Scientific Affairs of RenovaCare, Inc.
1. Nussbaum SR, Carter MJ, Fife CE, et al. An economic evaluation of the impact, cost, and Medicare policy implications of chronic non-healing wounds. Value Health. 2018;21(1):27–32.
2. International Diabetes Federation. About diabetes. Available at https://www.idf.org/aboutdiabetes/what-is-diabetes/facts-figures.html.
3. American Podiatric Medical Association. What is a diabetic foot ulcer? Available at https://www.apma.org/diabeticwoundcare .
4. Memmel H, Kowal-Vern A, Latenser BA. Infections in diabetic burn patients. Diabetes Care. 2004; 27(1):229-33.
5. Dolp R, Rehou S, Pinto R, et al. The effect of diabetes on burn patients: a retrospective cohort study. Crit Care. 2019; 23:28.
6. Gurtner GC, Chapman MA. Regenerative medicine: charting a new course in wound healing. Adv Wound Care. 2016; 5(7):314-28.
7. Rice JB, Desai U, Cumming AK, et al. Burden of diabetic foot ulcers for Medicare and private insurers. Diabetes Care. 2014; 37(3):651-8.
8. Walter + Eliza Hall Institute of Medical Research. Clinical translation. Available at https://www.wehi.edu.au/research/research-fields/clinical-translation.
9. Oldham B, Robinson R. A new approach to lessen diabetic wound complications. Chain Drug Rev. Available at https://www.chaindrugreview.com/a-new-approach-to-lessen-diabetic-wound-complications/.
10. Hara A, Sato D, Sahara Y. New governmental regulatory system for stem cell-based therapies in Japan. Ther Innov Regul Sci. 2014; 48(6):681-88.