Chirurgia Cosmetica Morfodinamica e bibliografia pertinente

La Chirurgia Cosmetica Morfodinamica e le sue tecniche si basano su concetti interdisciplinari provenienti dall’Anatomia Funzionale, Ortopedia e Crescita Cranio-Facciale, Meccanobiologia, Craniologia Funzionale, Proloterapia, su recenti acquisizione riguardo i complessi network neuromuscolari dei tessuti, su recenti ricerche riguardanti i biomateriali, la medicina rigenerativa e bioingegneria.
Il principio fondamentale della Chirurgia Cosmetica Morfodinamica è che: la funzione determina la forma. Ossia la morfologia del nostro viso (e ovviamente di tutto il corpo) è solo in parte dovuta a fattori genetici, le dinamiche dei complessi network neuromuscolari ne determinano lo sviluppo e l’evoluzione, per cui modificando queste dinamiche si ottengono notevoli cambiamenti (principio della matrice funzionale di Moss).
Il network neuro-muscolare mediante la stimolazione della matrice periostale causa la crescita diretta dell’unità microscheletrica (comprendente ossa, cartilagini e tessuti tendinei), il meccanismo di deposizione ossea e riassorbimento sotto carico porta ad effetti sulla misura e/o forma della struttura ossea. Come per i muscoli, infatti, che tendono a ingrossarsi e irrobustirsi col tempo a seguito di adeguati stimoli o ad atrofizzarsi in mancanza di tali, anche per le ossa il nostro corpo applica questo tipo di meccanismo.
È su queste concetti che si basano il metodo e le tecniche della Chirurgia Cosmetica Morfodinamica per ottenere rimodellamento dei tessuti, compresi muscoli ed ossa. Un altro principio fondamentale della Chirurgia Cosmetica Morfodinamica è la esclusione di incisioni chirurgiche lineari (come quelle della blefaroplastica e dei lifting), ove possibile. Questo perché le cicatrici lineari che residuano interrompono le fisiologiche dinamiche dei network neuromuscolari dando negli anni successivi esiti sgradevoli. Per ovviare a questo si dà grande rilievo a tecniche mini invasive come quelle dei fili.
Nel mondo dell’estetica gran parte delle procedure cercano di ottenere una blanda fibrosi per rassodare i tessuti cutanei e sottocutanei aumentando l’attività dei fibroblasti, ossia di quelle cellule deputate alla produzione di matrice connettivale. Quindi qualsivoglia filler (acido ialuronico, polilattico, policaprolattone, idrossiapatite, etc.), filo biostimolante o di trazione, radiofrequenza, ultrasuoni focalizzati e non, ozonoterapia, vari tipi di laser, biostimolazioni, etc. in misura maggiore o minore, hanno la finalità di stimolare la produzione endogena di collagene per ottenere dei tessuti più sodi ed un aspetto più giovanile.

In Chirurgia Cosmetica Morfodinamica vengono utilizzati fili di diversa composizione, a rapido (PDO, PLA) e lento riassorbimento (poliammide).
Secondo la United States Farmacopea le suture sono considerate riassorbibili quando sono dissolte in vivo entro sei mesi, oltre questo periodo sono considerate permanenti o non riassorbibili.
Tuttavia studi specialistici sul comportamento in vivo dei polimeri e biomateriali evidenziano che tra le suture non riassorbibili (poliammide, polietilene, poliestere, polivinildenefluoride, seta, …) la poliammide, grazie alla sua struttura polipeptidica e ai gruppi ammidici (ha una struttura chimica simile al collagene), e alla sua capacità di incorporare acqua fino al 10% della sua massa, è il materiale che subisce maggiormente il naturale processo di idrolisi in vivo (circa il 20-25% ad anno), per questi motivi la poliammide è il materiale più utilizzato in Chirurgia Cosmetica Morfodinamica.
La poliammide multifilamenti, non rivestita (quindi senza silicone, cera o altro) subisce il processo di idrolisi molto più intensamente rispetto alle suture monofilamento e alle suture multifilamenti rivestite. La struttura multifilamenti è composta da una miriade di filamenti sottilissimi intrecciati tra di loro, questa struttura insieme all’assenza di qualsiasi rivestimento favoriscono l’azione enzimatica (il polietilene è il più resistente, tra i polimeri il polimetilmetacrilato rimane intatto all’attività degli enzimi) (Karaka E. et al).
Infatti il formato monofilamento della poliammide viene adoperato quando si vuole ridurre al minimo le possibilità di riassorbimento, mantiene le proprie caratteristiche morfologiche e fisiche per molto più tempo, è indicato in cardiochirugia, gastroenterologia, oculistica, neurochirurgia, ortopedia, protesi capelli, etc. Il formato multifilamenti è più adatto per legature vasi, fascia, peritoneo, chirurgia plastica, chirurgia generale, quale medicazione di ferite croniche, etc. Per la sua alta biocompatibilità, capacità biomimetica e alta biodegradabilità, la poliammide viene applicato come veicolante di farmaci e supporto di tecniche rigenerative.
Il Prof. Karaka, Department of Textile Engineering, Faculty of Engineering and Architecture, Uludag University, in una delle sue pubblicazioni scrive” Among the synthetic nonabsorbable sutures, polyamides are probably the one most susceptible to degradation in vivo”.
Lo stesso tipo di materiale viene adoperato dal Prof. Nikolay Serdev, autore di numerose pubblicazioni su tecniche mini invasive. Le sue suture in polycaproamide vengono descritte nel libro del dott. Bacci “semipermanenti e semielastiche, a lento riassorbimento, dai 3 ai 5 anni” (Bacci, La bellezza appesa ad un filo. Minelli Editore. Pag 49).
Le Sedev Suture Polycon sono realizzate in poliammide (polycaproamide) bulgaro con aggiunta di un antimicrobico, sono semielastiche ed assorbibili a lungo termine (2-3 anni), sul sito Medical Devices Int. si legge: “Long-term Absorbable – the surgical threads are absorbed in the human body within two years” ( https://medicaldevices-bg.com/surgical-sutures/). La policaproammide è uno specifico tipo di poliammide (nylon 6).
La poliamide 6 (PA6, Nylon6, da cycloexanone via e-caprolactam) e la poliammide 6,6 (PA66, Nylon6,6, da adipic acid e hexamethylene ), specialmente nella forma intrecciata e non rivestita, possono essere considerate “materiale a lento riassorbimento”, grazie alla loro idrofilia e suscettibilità alla degradazione idrolitica in vivo. La poliammide 6 assorbe circa il 9-10% di acqua, la poliammide 6,6 il 4-5% di acqua. Entrambi questi materiali vengono utilizzati in vivo come impianti semidegradabili. La poliammide 6 si degrada in vivo più velocemente della poliammide 6,6 per idrolisi dei legami ammidici, un processo accelerato in ambienti fisiologici umidi e con enzimi specifici. Inoltre la PA6 ha una minore cristallinità (~40%) rispetto alla PA66 (~50-55%). Una minore cristallinità significa che la PA6 ha più regione amorfe, dove l’acqua può penetrare più facilmente e accelerare la degradazione idrolitica, questa è particolarmente presente in ambienti fisiologici con pH vicino alla neutralità o leggermente acido (come nei tessuti infiammati). Per tutti questi motivi la PA6 viene preferita alla PA66 per dispositivi medici impiantabili bioassorbibili proprio grazie alla sua biodegradabilità quando si vuole un più rapido riassorbimento e per questi motivi le suture in poliammide 6 vengono definite a “lento riassorbimento “, pur appartenendo alla categoria delle suture non riassorbibili.
Una delle complicanze più frequenti nella metodica di inserimento di fili chirurgici a lento riassorbimento è l’eccessiva fibrosi.
In caso di fibrosi in eccesso vanno effettuate infiltrazioni intralesionali di sostanze o farmaci con azione fibrinolitica o stimolante la rigenerazione dei tessuti.
Le sostanza e farmaci utilizzati sono: kenacort, ialuronidasi, collagenasi (PB Serum), 5-fluorouracile, eparina, pentossifillina, verteporfina, verapamil, imiquimod 5%, acido ialuronico, tossina botilinica, etc. È possibile utilizzare tecniche rigenerative con fattori di crescita (PRP naturali o biomimetici) con cellule staminali prelevate dal grasso autologo: (microfat e nanofat), etc.
Dopo diversi mesi nelle fibrosi possono precipitare sali minerali creando delle calcificazioni, in tal caso si adopera:
▪ il tiosolfato sodico, molto efficace in tutte le lesioni da deposito di calcio (calcinosi),
▪ la pentossifillina, che aumenta la microcircolazione nei tessuti con placche calcificate e fibrotiche, riduce il deposito di collagene I e riduce la calcificazione.
La seconda possibilità terapeutica è la terapia sistemica con svariate sostanze, tra cui prednisolone, minociclina, allopurinolo, colchicine, ciclosporine, methotrexate, sostanze fibrinolitiche (serrapeptasi, etc) etc. Buoni risultati sono stati ottenuti anche con la terapia fotodinamica.

Come ultima possibilità c’è la chirurgia, ma solo se tutte le altre non hanno avuto successo. La chirurgia mai è la prima scelta, tranne in caso dei granulomi piogenici (di ben altra natura ed istologia). Eseguire chirurgia per rimuovere tessuto fibrotico senza aver prima tentato le metodiche conservative espone a maggiori rischi il paziente sia per le cicatrici residue che per i rischi insiti nella procedura chirurgica.

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Functional Bio-based Materials for Regenerative Medicine: From Bench to Bedside
Mohd Fauzi Mh Busra
Functional Bio-based Materials for Regenerative Medicine: From Bench to Bedside explores the use of bio-based materials for the regeneration of tissues and organs. The book presents an edited collection of 28 topics in 2 parts focused on the translation of these materials from laboratory research (the bench) to practical applications in clinical settings (the bedside). Chapter authors highlight the significance of bio-based materials, such as hydrogels, scaffolds, and nanoparticles, in promoting tissue regeneration and wound healing. Topics included in the book include: – the properties of bio-based materials, including biocompatibility, biodegradability, and the ability to mimic the native extracellular matrix. – fabrication techniques and approaches for functional bio-based material design with desired characteristics like mechanical strength and porosity to promote cellular attachment, proliferation, and differentiation – the incorporation of bioactive molecules, such as growth factors, into bio-based materials to enhance their regenerative potential. – strategies for the controlled release of molecules to create a favorable microenvironment for tissue regeneration. – the challenges and considerations involved in scaling up the production of bio-based materials, ensuring their safety and efficacy, and obtaining regulatory approval for clinical use Part 2 covers advanced materials and techniques used in tissue engineering. Topics focus on advanced composite materials for 3D scaffolds and the repair of tissues in different organs such as the heart, cornea, bone and ligaments. Materials highlighted in this part include polyamide composites, electrospun nanofibers, and different bio-based hydrogels. Functional Bio-based Materials for Regenerative Medicine: From Bench to Bedside is a valuable reference for researchers in biomedical engineering, cell biology, and regenerative medicine who want to update their knowledge on current developments in the synthesis and application of functional biomaterials.

Polyamide derived from terpenes: advances in their synthesis, characterization and applications. Winnacker M.

Polyamides are very important polymers, with applications from commodities up to high-performance materials for, for example, fibers or for the biomedical sector. Nowadays, still most of them are synthesized from fossil resources. With regards to sustainability and bioeconomy, and especially regarding the new structures and properties that can thus be achieved, the preparation of polyamides (PAs) from natural precursors is getting more and more important. 

Similar approaches are interesting from a scientific point of view regarding, for example, structure-function-relations, but also with regards to different applications as, for example, high-performance or biomedical materials.

Practical applications: Terpene-based polyamides can find many applications, from commodities up to high-performance fibers and special materials in (bio)medicine, for example, drug delivery, tissue engineering, etc.

Polyamide/PEG Blends as Biocompatible Biomaterials for the Convenient Regulation of Cell Adhesion and Growth
Winnacker M.
In addition to their established usage in textiles, commodities, and automotives, classical polyamides (nylons) are recently becoming increasingly interesting for applications in (bio)medicine. This fact relies on many prosperous properties of these polymers, which are toughness, resistance, biocompatibility, low immunogenicity, tunable biodegradability, and their similarity to natural peptides (amide bonds). Some nylon‐based medical products do already exist for wound treatment applications, implants, and biomolecule‐interacting membranes, but the systematic use of these polymers for tissue engineering is—although desired—still to be accomplished. Inspired by this, the suitability of nylon 6 and of a related biobased and more hydrophobic terpene‐derived polyamide as surfaces for the controlled interaction with HaCat cells (human keratinocytes) are investigated herein with regard to possible applications for regenerative skin replacement. The nylons are applied as neat polymers and as hydrophilized blends/composites with polyethylene glycol and confirm their excellent suitability as biomaterials. Polyamides (nylons), which have been used for textiles, commodities, and automotives for decades, are also becoming increasingly interesting for medical applications. Herein, novel blends consisting of a polyamide (nylon 6 or a biobased, terpene‐based polyamide) and polyethylene glycol (and a corresponding copolymer), as well as their interactions with human keratinocytes, are described. This approach is very promising with regard to skin tissue engineering.

Biobased polyamides: academic and industrial aspects for their development and applications Ullrich M.

Polyamides are very important polymers for a wide range of applications. In the context of Green Chemistry and the development of sustainable polymers from renewable resources, many polyamides have meanwhile been developed that are derived from natural building blocks. In addition to sustainability, biobased polyamides can have special structures and properties that cannot be obtained so easily via fossil-based pathways. This article gives an overview over the recent developments in this field and elucidates the potential of these polymers for different applications.

Transcutaneous scarless buttock lift via tha Serdev Suture Technique
Serdev N
Essential equipment consists of a long, curved, semi-elastic needle and Polycon No 4, 6 or 8 (elastic Bulgarian antimicrobial polycaproamide threads)

Insight into Mechanobiology: How Stem Cells Feel Mechanical Forces and Orchestrate Biological Functions.
Argentati C.
Mechanosensing
All organisms have evolved structures, enabling them to recognize and respond to mechanical forces. This cross-talk takes place at the macroscale level (e.g., in organs and tissues), at the microscale level(e.g., in single cells), and also at the nanoscale level(e.g., inmolecular complexes or single proteins). At present, we know that the different types of forces orchestrate the control of all biological functions, including stem cells’ commitment, determination, development, and maintenance of cells and tissues homeostasis.
Notably, between ECM and stem cells exists a dynamic cross-talk, as stem cells may change the ECM composition and remodel the architecture either by the secretion of ECM structural components and matrix metalloproteinases, or by exerting mechanical forces through the cytoskeleton f ibers. The challenge is to create a suitable cell microenvironment that generates mechanosensing/ mechanotransduction signals and guide stem cells’ functions.
The rationale of the use of biomaterials as stem cells support is based on the cross-talk taking place between them. Stem cells act on biomaterials releasing ECM proteins and bioactive molecules and exert forces through the cytoskeletal components to recreate their niche. Conversely, biomaterials act on stem cells through their intrinsic chemical-physical properties, which activate mechanosensing/mechano- transduction signalling and thereby modulate the stem cells fate. Different types of natural (e.g., collagen, fibrin, silk) and synthetic (e.g., polylactic acid, polyamide, polyesters, polyanhydrides, polyurethane) polymers have been manipulated to fabricate biocompatible films (two-dimensional) or scaffolds (three-dimensional) with tuneable properties to guide stem cells fate.
Mechanical cues activated by the ECM and translated to the cell through mechanosensing/mechano- transduction signals represent a general scheme by which cells, tissues, organs, and whole organisms respond to external mechanical stimuli orchestrating their biologic activity.
Advances in the use of biomaterials as support for in vitro stem cells cultures to generate ex-vivo models of tissues and organs, together with computational systems, have highlighted the potentials of mechanobiology as a new therapeutic tool to be investigated for RM applications.

Tissue engineering scaffold material of porous nanohydroxyapatite/polyamide 66
Qian Xu
Polyamide (PA) has good biocompatibility with human tissue, probably due to its similarity to collagen protein in chemical structure. It has been widely used in the biomaterials application of surgical sutures for
nearly half a century. Especially important, PA also exhibits excellent mechanical properties.

Composite scaffolds of mesoporous bioactive glass and polyamide for bone repair.

Jiacan Su

Polyamide (PA), a polymer with excellent biocompatibility, has been used to fill bone defects and to create porous scaffolds for bone tissue engineering.

Mechanical stimulation on mesenchymal stem cells and surrounding microenvironment in bone regeneration: regulations and applications.
Zhang Y
recent studies proves that external mechanical stimulation regulates bone marrow mesenchymal stem cells (BMSCs) toward osteogenic lineage which is independent of osteocytes regulation (Schreivogel et al., 2019). The bone defect first triggers an inflammatory process, which leads to the recruitment of mesenchymal stem cells (MSCs) to the bone defect by inflammatory factors. These MSCs then differentiate into cartilage that gradually ossifies with the growth of blood vessels into the cartilage model. Thus, MSCs play a crucial role in bone regeneration. MSCs regulate the immuno-microenvironment by interacting with macrophages and regulating blood vessel formation by secreting angiogenic growth factors. This process involves interacting cells, including MSCs, macrophages, and vascular endothelial cells, as well as extracellular matrix molecules and cytokines, all of which constitute the MSC niche that is of great significance in regulating bone regeneration (Moore and Lemischka, 2006; Kuhn and Tuan, 2010; Vafaei et al., 2017).
Previous studies have indicated that MSC differentiation was determined by the MSC niches (Chen et al., 2020). Moreover, recent studies have shown that MSC differentiation was also affected by mechanical stimulation (Ravichandran et al., 2017).
The lacunar-canalicular system (LCS) is filled with interstitial fluid (Timmins and Wall, 1977). Intramedullary pressurization alteration and deformation of bone matrix generate interstitial fluid flow (Kwon et al., 2010; Price et al., 2011; Ciani et al., 2014). Therefore, mechanical loading leads to variation in intramedullary pressurization, which results in shear stress generation. Shear stress applies to osteocytes in LCS and MSCs in the bone marrow. Fluid shear stress is the general form of the force applied to MSCs in the bone marrow under physiological conditions (Gurkan and Akkus, 2008). The form of the force applied to MSCs in the periosteum is mainly caused by micro-deformation of bone generated by external mechanical stimuli such as stretching and compression. MSCs respond to the stimulation indirectly by sensing the micro-deformation of the extracellular matrix. Therefore, when investigating the mechanism of the mechanical loading effect on MSC differentiation, the function of both the direct and indirect force ought to be considered.
A variety of mechanical stimuli can be applied to cells using flexible culture substrates as well as scaffolds or bioreactors with suitable mechanical properties.87, 259 Axial, biaxial and cyclic static stresses have been used to induce cell proliferation.251 Studies have shown that cyclic mechanical strain is determinant in the control of the assembly of cells grown on flexible substrates.260, 261

Stem Cell Mechanobiology and the Role of Biomaterials in Governing Mechanotransduction and Matrix Production for Tissue Regeneration.
Naqvi S.
In conclusion, the future of regenerative medicine is based on (creation of metods) (the fabrication of innovative devices) that take into account the feedback between stem cells biology, cell sensing of force, and biomaterials‟ properties (topography, stiffness, electrical conductibility, in vivo behavior, drugs release and form).

Intralesional Injection Therapy and Atypical Peyronie’s Disease: A Systematic Review.
Choi EJ
Overall, 1,357 patients with PD were treated with intralesional therapy, of which 250 patients were considered to have an atypical presentation. 162 (648%) of the patients were treated with intralesional collagenase Clostridium histolyticum, 49 (19.6%) with verapamil, 29 (11.6%) with interferon alfa-2b, 5 (2.0%) with hyaluronic acid, and another 5 (2.0%) with onabotulinumtoxinA.

Intralesional and topical treatments for Peyronie’s disease: a narrative review of current knowledge.
Minore A
effectiveness and safety profiles of collagenase Clostridium histolyticum (CCH), interferon, platelet-rich plasma (PRP), hyaluronic acid, botulinum toxin, stem cell, extracorporeal shock wave therapy (ESWT), and traction therapy

Intralesional injection of adipose-derived stem cells reduces hypertrophic scarring in a rabbit era model
Zhang Q
Myofibroblast differentiation is another intensifier of fibrosis during wound healing. Myofibroblasts, differentiated from fibroblasts in an injury environment, are intended for narrowing the margin of the wounds and accelerating the re-epithelialization by contraction. However, at the same time, they produce tensed, excessive, and irregularly arranged collagen bundles and bring on over-contraction that characterizes hypertrophic scars [14, 15]. Prolonged wound healing usually results in hypertrophic scarring. Consequently, it is very important to ensure the formation of an adequate microvascular network and development into a permanent vascular network during the healing process; otherwise, wound closure will be impaired and hypertrophic scars will occur [16].

Cells biomodulation: the future of Dermatology.

Antonio CR
The anti-inflammatory action of botulinum toxin in the cutaneous vascularization reduces the inflammatory phase of the cicatricial process; besides, its action in fibroblasts and in the expression of TGF-beta1 acts improving the appearance of the scar.
Pruritus, present in many dermatologic conditions, when peripherally induced (pruriceptive pruritus) shows significant improvement with the application of intradermal botulinum toxin. 19 The molecular mechanisms involved in the improvement of pruritus with botulinum toxin are mast cell stabilization and inhibition of its degradation caused by BonT
in areas affected with hair rarefaction, there is relative hypoxemia, slower capillary filling and high levels of dihydrotestosterone. 27 The enzymatic conversion of testosterone into dihydrotestosterone depends on oxygen. In low concentrations of oxygen, the conversion is favored, leading to increased hair loss, whereas in high concentrations of oxygen, the favored conversion is testosterone into estradiol, favoring reduction of hair loss. Therefore, the application of botulinum toxin in the scalp reduces the vascular pressure when reducing muscular tone, creating increased local vascular flow and, consequently, increased oxygen, which reduces the enzymatic conversion of testosterone into dihydrotestosterone