Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / @xirurgi_2025 / @xirurgi_2025 - 1037 - файл
.pdf
106 B. Cheng and X. Fu
Xia Y, Zhao J, Xie J, et al. The efficacy of platelet-rich plasma dressing for chronic nonhealing
ulcers: a meta-analysis of
(6):1463–74.
Yammine K, Ghanimeh J, Jil A S, et al. PRP versus standard of care for venous leg ulcers: a
systematic review and meta-analysis of prospective comparative studies. Int J Low Extrem
Wounds. 2022;2143344152.
Yang S, Geng Z, Ma K, et al. Efficacy of topical recombinant human epidermal growth factor for
treatment of diabetic foot ulcer: a systematic review and meta-analysis. Int J Low Extrem
Wounds. 2016;15(2):120–5.
Yang Q, Zhang Y, Yin H, et al. Topical recombinant human epidermal growth factor for diabetic
foot ulcers: a meta-analysis of randomized controlled clinical trials. Ann Vasc Surg.
2020;62:442–51.
Zhang Y, Deng H, Tang Z. Efficacy of cellular therapy for diabetic foot ulcer. Cell Transplant.
2017a;26(12):1931–9.
Zhang Y, Deng H, Tang Z. Efficacy of cellular therapy for diabetic foot ulcer. Cell Transplant.
2017b;26(12):1931–9.
Zhang L, Zhang B, Liao B, et al. Platelet-rich plasma in combination with adipose-derived stem
cells promotes skin wound healing through activating Rho GTPase-mediated signaling
pathway. Am J Transl Res. 2019;11(7):4100–12.
Zhao XH, Gu HF, Xu ZR, et al. Efficacy of topical recombinant human platelet-derived growth
factor for treatment of diabetic lower-extremity ulcers: systematic review and meta-analysis.
Metabolism. 2014;63(10):1304–13.
15 randomized controlled trials. Plast Reconstr Surg. 2019;144
Physical, Electromagnetic, Biologic
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Devices
Alberto Piaggesi
Abstract
The inception of Physical, Electromagnetic and Biologic devices into the field of
wound management has greatly changed the standard approach to wound
healing—only think of negative pressure wound therapy. This and other
innovations introduced a completely different approach both on diagnostic and
therapeutic aspects of this multi-specialistic area, in a variety of conditions all
characterized by chronic ulceration. The number and variety of medical devices
focused on wound management would deserve a thorough evaluation and
description, which is beyond the scope of this report, in which a synthesis of the
more relevant among the new technologies applied so far in the clinical field,
reporting also their level of evidence, addressing the reader to the relevant
literature.
Keywords
Bio-PhysicElectromagnetismBiologic DevicesWound management
Evidence
A. Piaggesi (&)
Diabetic Foot Section, Department of Medicine, University of Pisa, Pisa, Italy
e-mail: alberto.piaggesi@med.unipi.it
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
R. Mani (ed.), Chronic Wound Management,
https://doi.org/10.1007/978-3-031-26110-7_6
107
108 A. Piaggesi
Introduction
The ways and the extent at which new technologies influenced the practice of
wound management progressively increased in the last years, changing both
diagnosis and therapy of a number of different pathologies, all characterized by the
presence of chronic wounds (Mani et al. 2016).
The impact of this reevolution has been so relevant that the European Wound of
Management Association (EWMA), a scientific society focused on wound management, decide to edit two documents dedicated to this topic; the first, entitled
Advanced Therapies in Wound Management, was published in 2018 (Piaggesi et al.
2018), while the second, entitled New Technologies for Tissue Replacement, will be
published in September 2022 as a supplement of the Journal of Wound Management (Piaggesi et al. 2022).
In these two documents, both edited by the author of this chapter, a panel of
experienced and extremely qualified authors synthetized both the technical and
clinical features of many classes of devices and technologies related to wound
management, from physical –related technologies to new materials, to dermal and
bone substitutes to nanotechnologies to internet-related technologies. The importance of this contribution is evident when one thinks of the increasing number of
patients with chronic wounds and complex cases, which deserve effective solutions,
to the cost-effectiveness of the interventions, to the new medical technology rules,
which have drastically changed the scenario of medical devices in Europe (Rayman
et al. 2019; Lindholm and Searle 2016).
To adequately address the new technologies in wound management an
exhaustive research on the most important databases has been carried out, in order
to sort out the evidence behind the technologies and evidence tables for any section
were produced as a support for the readers, alongside the reference tables, in which
all the papers included in the analysis were synthetically summarized.
A similar approach will be followed in this display, in which the most important
chapters of the documents will be synthetized, providing the relative evidence
tables.
Physical/Delivery Systems
The inception of physical means into the management of chronic ulceration was
actually a game changer, since it opened to a brand-new philosophy behind diagnosis and treatment of these complex conditions, based on the interaction between
physical forces and the biology of the lesions, rather than on chemical and /or
biochemical reactions. This was in a way a revolution, because the easiness of
supplying, the re-usability, the lack of direct contact and the wide range of solutions, from electric and electro-magnetic fields to light and lasers, ionic plasma to
fluorescence, made it possible to re-shape the diagnostic and therapeutic strategies
Physical, Electromagnetic, Biologic Devices 109
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Fig. 1 Auto fluorescence (left to right). In a chronic infected lesion, where it is difficult to identify
biofilm and infected site to be debrided, the illumination with Infrared polarized light activate
auto-fluorescence in eucariotic cells and bacteria, which react producing light at different
wavelengths, thus separating the infected areas (cyan green) from healthy granulating tissue (dark
green) (Anghel et al. 2016)
in many different complex situations. This has improved our possibility of curing
the patients.
Either the diagnostic approach, with new ecographic-based technologies and
point-of care detectors (Fig. 1) (Pieruzzi et al. 2020; Anghel et al. 2016) and
therapy, with a wid e range of new possibilities (Ennis et al. 2016) has been deeply
affected.
More recently, besides the physical technologies strictu sensu, also delivery
systems and materials came into play, opening new possibilities for patients suffering from chronic wounds.
For the sake of the exposition, the different technologies have been grouped
according to their basic physical principles; In Table 1 the most important physical
technologies and delivery systems are reported together with their level of evidence.
according to SORT system, ranging from 1A (= more than 1 randomized controlled
trial) to 4 (= expert opinion).
Materials
Tissue replacement relies on natural or artificial tri-dimensional (3D) matrices that
provide a temporary template for the invasion of host cells that gradually deposit
their own matrix and neo tissue. Naturally, a successful interaction with host cells is
expected to be reached if they encounter a support that resembles their own
extracellular matrix (ECM) maximizing their response. In fact, ECM-derived
110 A. Piaggesi
Table 1 Evaluation of evidence levels: physical technologies for tissue replacement (VLU = venous leg ulcers; PU = pressure ulcers; DFU = diabetic foot ulcers)
Technology Indication Level of
Autofluorescence VLU,
Hyperspectral imaging VLU,
Cold atmospheric
plasma
Blue light VLU,
Light activated nanofiber
textile
Electric stimulation PU 1B Solid evidence in vitro and in animal
Topical oxygen,
magnetic stimulation
and low-energy light
Injectable hydrogels ––Too early to be proposed for clinical
PU, DFU
PU, DFU
VLU,
PU, DFU
DFU
VLU 2B Good preliminary results in a pivotal
VLU 1C Positive results in one RCT and in one
evidence
1C Preliminary positive results, both
1B Positive results both in vitro and
1B Positive findings in clinical trials,
1C Good evidence in vitro, preliminary
Comments
in vitro and in clinical trials
in vivo, some initial clinical evidence
no RCT at present
good evidence in pre-clinical models
positive results in observational
studies
clinical experience
models, positive results in one RCT
observational trial
applications, but extremely promising
structures to which cell s were removed while preserving (not completely) native
structure and composition, can be considered the gold standard of dermal templates.
Additionally, ECM has been the source of components that are combined in various
formulations and then processed/manufactured as 3D porous structures to form
scaffolds that tend to provide the elements that stand out in the native tissue, to get
improved clinical performance (Casey 2002).
ECM has been the font of inspiration for the development of artificial (bio)-
materials, but it is not evident if these have superior performance than the
ECM-derived ones or if that depends on the application/tissue to be healed (Luo
and Wu 2020).
The properties of artificial materials are highly controlled in opposition to the
variability associated to natural sources, allowing the use of a greater number of
processing methodologies to generate 3D stru ctures that can act as tissue templates.
Nonetheless, this is also directly linked to thei r bioactivity since the coupling of
biomolecules/cues to those materials narrows that window. Therefore, a
well-balanced compromise between bioactivity/ECM resemblance and processing
conditions, is required in the development of tissue templates with a maximized
potential for tissue replacement (Rudge 1999). In Table 2 the most important
technologies on biomaterials are reported, together with their level of evidence.
Physical, Electromagnetic, Biologic Devices 111
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Table 2 Evaluation of evidence levels of biomaterials-based technologies for tissue replacement
Technology Indication Level of
Acellular Dermal
or non-dermal
Matrices
Acellular Dermal
Matrix
Acellular Dermal
Matrix
Artificial Matrices Burns 2C Few RCT with weak evidence; likely to
Non-living tissue
derived matrices
Extracellular
Matrix-derived
Biomaterials
Bioprinting
(cellular skin
substitutes)
3D printing ––Relevant results of customised prosthesis
DFU 1B High-quality studies and good evidence of
VLU 2C Few RCT with weak evidence; likely to
Burns 2C Few RCT with weak evidence; likely to
Complex
DFU
Wounds
––Promising in vivo indications regarding the
––Promising in vivo indications in promoting
evidence
2B Positive results non-RCT studies and case
Comments
effectiveness despite variabilities among
trials
perform equal to other technologies
perform equal to other technologies
perform equal to other technologies
series regarding the healing of bone and/or
tendon tissues during wound closure
importance of biomaterials responding to
specific wound features (vascularization;
inflammation)
wound closure and neovascularization,
potentially reducing scarring
(Bone and device for NPWT) in feasibility
clinical studies but limited use as
regenerative templates for wounds
Skin Substitutes
Since the last three decades the acellular dermal substitutes have changed the
concept of skin reconstruction. The neo-dermal component forming the dermal
substitute limits the secondary retraction of the thin autologous skin graft used to
cover it. Many products have been proposed and they can be with or without
elastin, their collagen can come from different animals like cows, fish, or pigs with
different combination with elastin, and they can be covered by a protective film in
silicone and secondarily skin grafted after 3 weeks. This period is fundamental in
order to permit scaffold’s degradation and consequently the formation of a new
functional tissue which can avoid scar formation (Dai et al. 2020).
The heterogeneity of the different dermal substitutes and their different indica-
tions make the global perception of these medical devices somehow confusing
starting from their classification. Skin substitutes can be classified as epidermal,
dermal, and composite, and further split into different categories depending on their
composition and source of material (xenograft, acellular allograft, cellular allograft,
autograft, synthetic skin substitutes), contraction capacity, pores size, and shape
112 A. Piaggesi
Table 3 Level of evidence of skin substitute based on the last 5 years of references
Dermal substitute Level of
Integra 3b Positive results from case series and retrospective studies.
Matriderm 3b Positive results from case series and retrospective studies
Nevelia 4 Positive results from case series
Pelnac 3b Positive results from retrospective studies. Few
Kerecis 4 Positive results from case series
Dehidrated
amniotic
Membrane
Apligraf 5 Narrative reviews, only one RCT
Oasis N/A Positive results from case reports, only 1 RCT
DeNovo skin N/A Phase I trial
Evidence
3b Positive results from case series retrospective studies.
Comments
Few prospective and/or randomized control trials
prospective or randomized clinical trials
Few randomized control trials
(Goodarzi et al. 2018). Because there is no ideal option for skin substitutes there are
many resear ches evaluating and developing different skin substitute options
(Límová 2010).
In Table 3 the different options in the field of skin substitutes, with the relative
evidence are reported.
Bone Substitutes
It has been estimated that 60% of diabetic foot ulcerations (DFU) are infected at the
time of initial evaluation (59). In the setting of osteomyelitis and/or soft tissue
infection, antibiotic therapy most often in conjunction with surgical debridement of
infected, non-viable tissue and bone is the usual initial course of treatment. In
addition to debridement and systemic antibiotic therapy, local antibiotic delivery
via non-absorbable/non-resorbable bone cement polymethyl-methacrylate (PMMA)
and absorbable/resorbable bone graft substitutes may be a beneficial adjunct to
surgical treatment of osteomyelitis in patients with infected diabetic foot ulceration.
Antibiotic impregnated cement has been used for many years, and recently
resorbable bone graft substitutes have been utilized in the treatment of diabetic foot
osteomyelitis (DFO). The addition of this method for local delivery of antibiotics
during the surgical treatment of DFO may help improve outcomes and reduce
amputation rates (Fillingham and Jacobs 2016).
There are several challenges that can occur with surgi cal resection of infected
tissue/bone and systemic antibiotic therapy. The use of local antibiotic delivery via
non-resorbable and resorbable carriers may help mitigate these potential issues. The
decision to surgically resect infected bone is dependent on several variables to
Physical, Electromagnetic, Biologic Devices 113
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
include location of osteomyelitis, specialty of the provider and available resources.
The extent of debridement is also an area of debate as some advocate for total
resection and clean margins, while others perform limit ed bone resections. Surgical
excision of infected bone can result in dead space and/or bone defects, which can
impact skeletal stability. In addition, despite surgical debridement, residual
microorganisms may remain at the site of infection (i.e. positive margins). It is also
thought that biofilm related to long standing diabetic foot ulceration may have a role
in the development of chronic DFO, serving as a barrier to systemic antibiotic
(Campana et al. 2014). Systemic antibiotics can lead to complications such as renal
toxicity, bacterial resistance and gastrointestinal dysfunction. In theory, local
delivery of antibiotics may provide several benefits compared to oral and intravenous antibiotic therapy. Local delivery can lower the risk for systemic complications and can result in increased concentration of antibiotic at the infection site
which is especially beneficial in the setting of peripheral arterial disease. Local
antibiotic delivery systems can elude a higher concentration of local antibiotics to a
site of infection, as much as 10 to 100 times greater than the minimum inhibitory
concentration. When used as a bone substitute, they can also fill a void or dead
space left by resection of bone and tissue (Busch et al. 2021).
Local antibiotic delivery systems in the form of cement and bone graft substi-
tutes have been widely used and described in the orthopedic literature. Few studies
have been published regarding their role in the surgical treatment of DFO. Recently
a new class of bone substitutes, called bio-glasses because of their derivation from
medical glasses for human use, have proven to be effective to treat osteomyelitis
(OM) in DFU, without the need for using local antibiotics (Fig. 2) (Iacopi et al.
2022). In Table 4 the recent evidence for local antibiotic delivery systems, with a
focus on the role of the newer resorbable bone graft substitutes and their potential
benefits in the surgical management of DFO is reported.
Fig. 2 Bioglass (left to right). In an acutely infected calcaneal bone in a DFU, after drastic
debridement and elimination of all the infected bone, the inception of bioglass granules leads to the
sterilization of the osteomyelitic focus and to the formation of new healthy bone, with complete
restitutio ad integrum (Iacopi et al. 2022)
114 A. Piaggesi
Table 4 Levels of Evidence for non-resorbable bone cement (PMMA) and resorbable bone graft
substitutes for local antibiotic delivery used for the surgical treatment of diabetic foot osteomyelitis
Number Therapy Indication for use Level of
1 Non-resorbable bone
cement for local antibiotic
delivery (PMMA)
2 Resorbable bone graft
substitutes for local
antibiotic delivery
3 Bioactive Glass Surgical treatment
Surgical treatment
of diabetic foot
osteomyelitis
Surgical treatment
of diabetic foot
osteomyelitis
of diabetic foot
osteomyelitis
evidence
4 Small numbers,
4 Small numbers,
4 Small numbers,
Comments
case series,
retrospective
case series,
retrospective
case series,
retrospective
Vascular-Related Technologies
In 2015, occlusive peripheral arterial disease (PAD) was diagnosed in 236,62
million adults older than 25 year of age world-wide. The prevalence, estimated
between 4 et 20%, varies according to, age, smoking habits, diabetes, high blood
pressure, hypercholesterolemia and social status. Of these patients 5–10% will
develop chronic limb-threatening ischemia (CLTI) within five years.
CLTI patients are at high risk of amputation and death. PAD is often under-
diagnosed. In a retrospective German study based on statutory health scheme 81%
of patients received a vascular diagnostic measure and only 50% had a vascular
procedure before amputation. To improve limb salvage and life there is a consensus
to proceed to a revascularization whenever feasible, which has been proved to be
effective in short and long term (Beckman et al. 2021).
The strategies of CLTI management have been reviewed thoroughly by inter-
national societies which issued recommendations concerning the grading of the
diseases, prognosis, explorations, treatments and follow-up (Rogers and Laird
2007). In Table 5 the evidence of vascular-related technologies is reported.
Conclusions
Despite the extreme interest and variety of new technologies in wound management
field, still evidence is scarce and of poor quality and their implementation in clinical
practice, despite being potentially useful, is negatively conditioned by the lack of
solid data in support.
New, more solid and prospective randomized trials are expected to finalize the
inception of many of these technologies in many different pathologies characterized
by chronic wounds.
Physical, Electromagnetic, Biologic Devices 115
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Table 5 Vascular-related technologies and their evidence
Technology Indication Level of
Conservative
treatment
Bypass Long lesions,
Balloon
angioplasty
Bare stent Short and medium
Drug coated
balloon
Drug eluting
stent
Covered
stents
Atherotom Calcified lesions 2C More data required
Cellular
therapies
Frail or
Non-revascularisable
patients
saphenous vein
available
Short lesions 2C Used as a primary option
length lesions
Short and medium
length lesions
Short and medium
length lesions
Long lesions 2B More data required
Non-revascularizable
CLTI patients
evidence
1C High Mortality and/or amputation
1A More durable option, Incisional
2B Used as a bailout procedure
1A Improved patency
1A Improved patency
1C Few long-term adequately
Comments
Wound healing problems
But safety uncertainty
But safety uncertainty
dimensioned studies
Too short follow up
Lack of comparative studies
References
Anghel EL, Falola RA, Kim PJ. Fluorescence technology for point of care wound management.
Surg Technol Int. 2016;28:58–64. PMID: 27175815.
Beckman JA, Schneider PA, Conte MS. Advances in revascularization for peripheral artery
disease: revascularization in PAD. Circ Res. 2021;128(12):1885–912.
Busch A, Jäger M, Mayer C, Sowislok A. Functionalization of synthetic bone substitutes. Int J
Mol Sci. 2021;22(9):4412.
Campana V, Milano G, Pagano E, Barba M, Cicione C, Salonna G, Lattanzi W, Logroscino G.
Bone substitutes in orthopaedic surgery: from basic science to clinical practice. J Mater Sci
Mater Med. 2014;25(10):2445–61.
Casey G. Wound repair: advanced dressing materials. Nurs Stand. 2002;17(4):49–53; quiz 54, 56.
Dai C, Shih S, Khachemoune A. Skin substitutes for acute and chronic wound healing: an updated
review. J Dermatolog Treat. 2020;31(6):639–48.
Ennis WJ, Lee C, Gellada K, Corbiere TF, Koh TJ. Advanced technologies to improve wound
healing: electrical stimulation, vibration therapy, and ultrasound-what is the evidence? Plast
Reconstr Surg. 2016;138(3 Suppl):94S–104S.
Fillingham Y, Jacobs J. Bone grafts and their substitutes. Bone Joint J. 2016;98-B(1 Suppl A):6–9.
Goodarzi P, Falahzadeh K, Nematizadeh M, Farazandeh P, Payab M, Larijani B, Tayanloo Beik A,
Arjmand B. Tissue engineered skin substitutes. Adv Exp Med Biol. 2018;1107:143–88.
Iacopi E, Pieruzzi L, Goretti C, Piaggesi A. Pilot experience on the use of S53P4 bioactive glass in
the surgical management of diabetic foot osteomyelitis. Int J Low Extrem Wounds. 2022;21
(1):57–64.
Соседние файлы в папке @xirurgi_2025