Chronic Leg Ulcers: Are Tissue Engineering and Biomaterials Science the Solution?

Chronic leg ulcers (CLUs) are full thickness wounds that usually occur between the ankle and knee, fail to heal after 3 months of standard treatment, or are not entirely healed at 12 months. CLUs present a considerable burden on patients, subjecting them to severe pain and distress, while healthcare systems suffer immense costs and loss of resources. The poor healing outcome of the standard treatment of CLUs generates an urgent clinical need to find effective solutions for these wounds. Tissue Engineering and Biomaterials Science offer exciting prospects for the treatment of CLUs, using a broad range of skin substitutes or scaffolds, and dressings. In this review, we summarize and discuss the various types of scaffolds used clinically in the treatment of CLUs. Their structure and therapeutic effects are described, and for each scaffold type representative examples are discussed, supported by clinical trials. Silver dressings are also reviewed due to their reported benefits in the healing of leg ulcers, as well as recent studies on new dermal scaffolds, reporting on clinical results where available. We conclude by arguing there is a further need for tissue-engineered products specifically designed and bioengineered to treat these wounds and we propose a series of properties that a biomaterial for CLUs should possess, with the intention of focusing efforts on finding an effective treatment.

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Causes and the way of treatment of patients with chronic leg ulcers

Phlebologie ◽

10.1055/s-0037-1622275 ◽

2009 ◽

Vol 38 (05) ◽

pp. 211-218 ◽

Cited By ~ 2

Author(s):

C. Wax ◽

A. Körber ◽

J. Dissemond ◽

J. Klode

Keyword(s):

Treatment Period ◽

General Practitioners ◽

Peripheral Arterial Occlusive Disease ◽

Mean Value ◽

Arterial Occlusive Disease ◽

Leg Ulcer ◽

Leg Ulcers ◽

Patient Will ◽

Peripheral Arterial ◽

Chronic Leg Ulcers

SummaryChronic leg ulcer may have various causes, which are currently not centrally recorded in Germany. It is also unclear who treats patients with chronic leg ulcers in Germany and how the basic implementation of diagnosis and treatment of these patients looks like. Patients, methods: Therefore, we started a survey of 1000 general practitioners and practising specialists in dermatology, surgery and phlebology in five different regions of Germany. We carried out the genesis of a total of 6275 patients from 62 different practising therapists, 33 specialists in dermatology, surgery or phlebology and 29 general practitioners. Results: In 66.1% of all patients we found a venous leg ulcer, in 9.1% a leg ulcer from peripheral arterial occlusive disease, and in 8.5% a mixture of both. Thus there suffered a total of 83.8% of patients on chronic venous insufficiency or peripheral arterial occlusive disease as a major factor in the genesis of the chronic leg ulcer. However, even the rarely diagnosed entities such as exogenous factors, vasculitis, pyoderma gangrenosum or infectious diseases are occur in summation in 16.2% of all patients and should therefore be known and excluded. In addition, the treatment periods and referral routes of patients with chronic leg ulcer should be identified. The analysis showed that the vast majority (86.8%) of patients with chronic ulcers who were investigated by us is treated by specialists. The treatment duration of general practitioners is 6.3 weeks (mean value) before the patient will be referred to a specialist. This treatment period is significantly shorter compared to the treatment period of the specialists, who treat their patients 14.1 weeks (mean value) before the patient will be referred to another specialist or to a clinic. Conclusion: Our results show the current aspects of aetiology and the way of treatment of patients with chronic leg ulcers in Germany.

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Ulcer osteoma and periosteal reactions to chronic leg ulcers.

American Journal of Roentgenology ◽

10.2214/ajr.168.1.8976939 ◽

1997 ◽

Vol 168 (1) ◽

pp. 155-157 ◽

Cited By ~ 9

Author(s):

D Karasick ◽

M E Schweitzer ◽

D M Deely

Keyword(s):

Leg Ulcers ◽

Chronic Leg Ulcers

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Effectiveness of an extracellular matrix graft (OASIS Wound Matrix) in the treatment of chronic leg ulcers: A randomized clinical trial

Yearbook of Vascular Surgery ◽

10.1016/s0749-4041(08)70616-x ◽

2007 ◽

Vol 2007 ◽

pp. 361-362

Author(s):

J.D. Raffetto

Keyword(s):

Clinical Trial ◽

Extracellular Matrix ◽

Randomized Clinical Trial ◽

Leg Ulcers ◽

Wound Matrix ◽

Chronic Leg Ulcers

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FRI0073 Topical nerve growth factor for the treatment of chronic leg ulcers in rheumatoid arthritis

10.1136/annrheumdis-2001.1202 ◽

2001 ◽

Author(s):

S Generini ◽

M Tuveri ◽

L Aloe ◽

M Matucci Cerinic

Keyword(s):

Rheumatoid Arthritis ◽

Nerve Growth Factor ◽

Growth Factor ◽

Leg Ulcers ◽

Nerve Growth ◽

Chronic Leg Ulcers

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Harnessing wound healing and regeneration for tissue engineering

Biochemical Society Transactions ◽

10.1042/bst0330413 ◽

2005 ◽

Vol 33 (2) ◽

pp. 413-417 ◽

Cited By ~ 35

Author(s):

A.D. Metcalfe ◽

M.W.J. Ferguson

Keyword(s):

Tissue Engineering ◽

The Body ◽

Biomedical Science ◽

Diabetic Foot Ulcers ◽

Mouse Mutant ◽

Skin Substitutes ◽

Skin Tissue Engineering ◽

Engineered Tissue ◽

Ear Injury ◽

Molecular Manipulation

Biomedical science has made major advances in understanding how cells grow into functioning tissue and the signalling mechanisms used to achieve this are slowly being dissected. Tissue engineering is the application of that knowledge to the building or repairing of organs, including skin, the largest organ in the body. Generally, engineered tissue is a combination of living cells and a supporting matrix. Besides serving as burn coverings, engineered skin substitutes can help patients with diabetic foot ulcers. Today, most of these ulcers are treated with an approach that includes antibiotics, glucose control, special shoes and frequent cleaning and bandaging. The results of such treatments are often disappointing and ineffectual, and scarring remains a major problem, mechanically, cosmetically and psychologically. Within our group we are attempting to address this by investigating novel approaches to skin tissue engineering. We are identifying novel therapeutic manipulations to improve the degree of integration between a tissue engineered dermal construct and the host by both molecular manipulation of growth factors but also by understanding and harnessing mechanisms of regenerative biology. For the purpose of this summary, we will concentrate primarily on the latter of these two approaches in that we have identified a novel mouse mutant that completely and perfectly regenerates skin and cartilaginous components following ear injury. This experimental animal will allow us to characterize not only novel genes involved in the regeneration process but also to utilize cells from such animals in artificial skin equivalents to assess their behaviour compared with normal cells. This approach should allow us to create a tissue-engineered substitute, which more closely resembles the normal regional microanatomy and physiology of the skin, allowing better integration to the host with minimal or no scarring.

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Stem Cell-Engineered Nanovesicles Exert Proangiogenic and Neuroprotective Effects

Materials ◽

10.3390/ma14051078 ◽

2021 ◽

Vol 14 (5) ◽

pp. 1078

Author(s):

Han Young Kim ◽

Suk Ho Bhang

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Mesenchymal Stem Cells ◽

Tissue Regeneration ◽

Therapeutic Agent ◽

Therapeutic Effects ◽

Hydrodynamic Size ◽

Regeneration Strategy ◽

Neuroprotective Effects ◽

The Poor

As a tissue regeneration strategy, the utilization of mesenchymal stem cells (MSCs) has drawn considerable attention. Comprehensive research using MSCs has led to significant preclinical or clinical outcomes; however, improving the survival rate, engraftment efficacy, and immunogenicity of implanted MSCs remains challenging. Although MSC-derived exosomes were recently introduced and reported to have great potential to replace conventional MSC-based therapeutics, the poor production yield and heterogeneity of exosomes are critical hurdles for their further applications. Herein, we report the fabrication of exosome-mimetic MSC-engineered nanovesicles (MSC-NVs) by subjecting cells to serial extrusion through filters. The fabricated MSC-NVs exhibit a hydrodynamic size of ~120 nm, which is considerably smaller than the size of MSCs (~30 μm). MSC-NVs contain both MSC markers and exosome markers. Importantly, various therapeutic growth factors originating from parent MSCs are encapsulated in the MSC-NVs. The MSC-NVs exerted various therapeutic effects comparable to those of MSCs. They also significantly induced the angiogenesis of endothelial cells and showed neuroprotective effects in damaged neuronal cells. The results collectively demonstrate that the fabricated MSC-NVs can serve as a nanosized therapeutic agent for tissue regeneration.

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Degradation of Antiproteinases, Complement and Fibronectin in Chronic Leg Ulcers: Investigative Report

Acta Dermato Venereologica ◽

10.1080/000155500750042925 ◽

2000 ◽

Vol 80 (3) ◽

pp. 179-184 ◽

Cited By ~ 32

Author(s):

Artur Schmidtchen

Keyword(s):

Leg Ulcers ◽

Investigative Report ◽

Chronic Leg Ulcers

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Tissue engineering of urethra: Systematic review of recent literature

Experimental Biology and Medicine ◽

10.1177/1535370217731289 ◽

2017 ◽

Vol 242 (18) ◽

pp. 1772-1785 ◽

Cited By ~ 2

Author(s):

Stanislav Žiaran ◽

Martina Galambošová ◽

L'uboš Danišovič

Keyword(s):

Systematic Review ◽

Tissue Engineering ◽

Clinical Trials ◽

Animal Studies ◽

Recent Literature ◽

Cell Attachment ◽

Experimental Studies ◽

Clinical Results ◽

Bioactive Molecules ◽

Urethral Reconstruction

The purpose of this article was to perform a systematic review of the recent literature on urethral tissue engineering. A total of 31 articles describing the use of tissue engineering for urethra reconstruction were included. The obtained results were discussed in three groups: cells, scaffolds, and clinical results of urethral reconstructions using these components. Stem cells of different origin were used in many experimental studies, but only autologous urothelial cells, fibroblasts, and keratinocytes were applied in clinical trials. Natural and synthetic scaffolds were studied in the context of urethral tissue engineering. The main advantage of synthetic ones is the fact that they can be obtained in unlimited amount and modified by different techniques, but scaffolds of natural origin normally contain chemical groups and bioactive proteins which increase the cell attachment and may promote the cell proliferation and differentiation. The most promising are smart scaffolds delivering different bioactive molecules or those that can be tubularized. In two clinical trials, only onlay-fashioned transplants were used for urethral reconstruction. However, the very promising results were obtained from animal studies where tubularized scaffolds, both non-seeded and cell-seeded, were applied. Impact statement The main goal of this article was to perform a systematic review of the recent literature on urethral tissue engineering. It summarizes the most recent information about cells, seeded or non-seeded scaffolds and clinical application with respect to regeneration of urethra.

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