Collagen Biomatrix Research Articles

Localized trans-browning and pro-angiogenesis inductive self-assembled collagen resveratrol bio-matrix for tissue repair and regeneration in obese conditions

The present study probes into the complexities of wound management in obesity by proposing a novel biomaterial designed to reprogram the altered skin physiology prevalent in obese conditions. The strategy involves the development of a multifunctional biomaterial addressing issues such as excessive exudate, pressure ulcers, and reduced vascularity. The bio-matrix demonstrates the localized transformation of white adipocytes through trans-browning, coupled with the simultaneous induction of angiogenesis at obese wound sites, resulting in expedited wound closure. The collagen bio-matrices, stabilized with Resveratrol (Rsv), exhibit remarkable thermal, mechanical, and biological stability. The porous 3D microstructure of the Rsv-stabilized collagen bio-matrix closely resembled the natural extracellular matrix, facilitating effective cell adhesion. The bio-matrix exhibited the unique capability to induce localized thermogenesis in the subcutaneous fat layer while concurrently activating angiogenesis. In vivo wound healing studies conducted on DIO-C57BL6 mice demonstrated complete healing within 10 days, showcasing accelerated tissue regeneration, blood vessel formation, robust collagen deposition, and significant activation of browning in the subcutaneous adipose layer. This study introduces the concept of tailored regenerative biomaterials with the ability to reprogram the challenging wound environment associated with obesity. This innovative approach opens up new avenues for enhanced wound care strategies, particularly for bariatric patients.

Apigenin Self-Assembled Collagen Biomatrix for Reprogramming the Obese Wound Microenvironment for Its Management and Repair.

Wound management in obesity is complicated by excessive exudates from wounded areas, pressure ulcerations due to stacking of the fat layer, and vascular rarefaction. The current study explored the development of biomaterials for reprogramming the altered wound microenvironment under obese conditions. Self-assembled collagen biomatrix with trans and de novo browning activator, apigenin, was fabricated as a soft tissue regenerative wound dressing material. The as-synthesized self-assembled collagen biomatrix exhibited excellent thermal, mechanical, and biological stability with a superior wound exudate absorption capacity. The apigenin self-assembled collagen biomatrix exhibited porous 3-D microstructure that mimicked the extracellular matrix that promoted cell adhesion and proliferation. The apigenin self-assembled collagen multifunctional biomatrix triggered adaptive localized thermogenesis in the subcutaneous fat layer, resulting in the activation of angiogenesis and fibroblast spreading and migration. The in vivo wound healing assay performed in DIO-C57BL6 mice showed faster tissue regeneration within 9 days, with well-defined neo-epidermis, blood vessel formation, thick collagen deposition, minimal inflammation, and significant activation of browning in the subcutaneous adipose layer. This study paves the way forward for the development of specialized regenerative biomatrices that reprogram the obese wound bed for faster tissue regeneration.

Decoupling the Influence of Poly(3,4-Ethylenedioxythiophene)-Collagen Composite Characteristics on Cell Stemness.

Conductive polymers (CPs) are widely studied for their ability to influence a myriad of tissue systems. While their mixed ionic/electronic conductivity is commonly considered the primary driver of these benefits, the mechanisms by which CPs influence cell fate remain unclear. In this study, CP-biomaterial interactions are investigated using collagen, due to its widespread prevalence throughout the body and in tissue engineering constructs. Collagen is functionalized with both electrostatically and covalently bound derivatives of the CP poly(3,4-ethylenedioxythiophene) (PEDOT) doped via backbone-tethered sulfonate groups, which enable high solubility and loading to the collagen biomatrix. Intrinsically doped scaffolds are compared to those incorporated with a commercially available PEDOT formulation, which is complexed with polyanionic polystyrene sulfonate (PSS). Low loadings of intrinsically doped PEDOT do not increase substrate conductivity compared to collagen alone, enabling separate investigation into CP loading and conductivity. Interestingly, higher PEDOT loading bolsters human mesenchymal stromal (hMSC) cell gene expression of Oct-4 and NANOG, which are key transcription factors regulating cell stemness. Conductive collagen composites with commercial PEDOT:PSS do not significantly affect the expression of these transcription factors in hMSCs. Furthermore, it is demonstrated that PEDOT regulates cellular fate independently from physical changes to the material but directly to the loading of the polymer.

Caffeine-reinforced Collagen as Localized Microenvironmental Trans-Browning Bio-Matrix for Soft Tissue Repair and Regeneration in Bariatric Condition.

The wound exudates, hypoperfusion of the subcutaneous fat layer, and poor vasculature worsen wound management in obese subjects. In the current study, a multifunctional Caffeine-reinforced collagen biomaterial is developed that can simultaneously modulate lipid metabolism and angiogenesis in obese wound microenvironments for faster tissue regeneration. The biomaterial is fabricated specialized for obese conditions to initiate simultaneous lipolysis and angiogenesis locally in the hypoxic subcutaneous fat in wound margins of obese subjects. Caffeine-reinforced collagen biomatrix shows better structural integrity, thermal stability, bio-compatibility, and lesser proteolytic susceptibility. Caffeine-collagen biomaterial promote angiogenesis, fibroblast migration, and localized browning of white adipocytes to activate thermogenesis in the subcutaneous fat layer at the wound site. Full-thickness excision wound healing studies performed in obese C57BL6 mice shows faster wound closure within day 9 when compare to control mice. The Caffeine-reinforced collagen biomaterial remodeled the wound site locally by activating fibroblast to secrete collagen, activate endothelial cells to promote angiogenesis, and induce browning in white adipocytes in subcutaneous fat. The study opens a new direction in bariatric tissue regenerative medicine by locally modulating lipid metabolism, angiogenesis, and trans-browning at the injured site for faster complete restoration of the damaged tissue.

Recent Approaches to the Modification of Collagen Biomatrix as a Corneal Biomatrix and Its Cellular Interaction

Over the last several decades, numerous modifications and advancements have been made to design the optimal corneal biomatrix for corneal epithelial cell (CECs) or limbal epithelial stem cell (LESC) carriers. However, researchers have yet to discover the ideal optimization strategies for corneal biomatrix design and its effects on cultured CECs or LESCs. This review discusses and summarizes recent optimization strategies for developing an ideal collagen biomatrix and its interactions with CECs and LESCs. Using PRISMA guidelines, articles published from June 2012 to June 2022 were systematically searched using Web of Science (WoS), Scopus, PubMed, Wiley, and EBSCOhost databases. The literature search identified 444 potential relevant published articles, with 29 relevant articles selected based on inclusion and exclusion criteria following screening and appraising processes. Physicochemical and biocompatibility (in vitro and in vivo) characterization methods are highlighted, which are inconsistent throughout various studies. Despite the variability in the methodology approach, it is postulated that the modification of the collagen biomatrix improves its mechanical and biocompatibility properties toward CECs and LESCs. All findings are discussed in this review, which provides a general view of recent trends in this field.

Hennotannic acid stabilised collagen bio-matrix for aberrant wound healing applications

The present study demonstrates the fabrication of Lawsone cross-linked collagen bio-scaffold for management of aberrant wound healing especially wound healing in post-surgical cancer margins. Lawsone reinforced with collagen resulted in increased thermal and mechanical stability, structural integrity, decreased proteolytic susceptibility and biocompatibility. It exhibited anti-angiogenic, anti-migratory and apoptotic effect selectively in cancer cells mediated by intrinsic increase of reactive oxygen species production in cancer cells. The biological properties exhibited by Lawsone cross-linked collagen bio-scaffold makes it a promising anti-cancerous wound dressing 3-D bio-matrix biomaterial for healing of postsurgical wound margins.

Lanthanum oxide nanoparticle-collagen bio matrix induced endothelial cell activation for sustained angiogenic response for biomaterial integration

Rare earth lanthanum oxide nanoparticle reinforced collagen biomatrix that elicited the endothelial cell activation to promote angiogenesis for biomaterial integration was developed and evaluated in the present study. The structural integrity of collagen was not compromised on crosslinking of lanthanum oxide nanoparticle to collagen biomolecule. As-synthesised collagen biomatrix was shown to have improved mechanical strength, a lesser susceptibility to proteolytic degradation and good swelling properties. Superior cytocompatibility, hemocompatibility and minimal ROS generation was observed with Lanthanum oxide nanoparticle reinforced collagen bio matrix. The Lanthanum oxide nanoparticle reinforced collagen bio matrix elicited endothelial cell activation eliciting pro-angiogensis as observed in tube formation and aortic arch assays. The bio-matrix promoted the infiltration and proliferation of endothelial cells which is an unexplored domain in the area of tissue engineering that is very essential for biomaterial integration into host tissue. The wound healing effect of Lanthanum oxide nanoparticle stabilized collagen showed enhanced cell migration in vitro in cells maintained in Lanthanum oxide nanoparticle reinforced collagen bio matrix. The study paves the way for developing rare earth-based dressing materials which promoted biomatrix integration by enhancing vascularisation for tissue regenerative applications in comparison with traditional biomaterials.

Assessment of Two Commonly used Dermal Regeneration Templates in a Swine Model without Skin Grafting

In the medical care of partial and full-thickness wounds, autologous skin grafting is still the gold standard of dermal replacement. In contrast to spontaneous reepithelializing of superficial wounds, deep dermal wounds often lead to disturbing scarring, with cosmetically or functionally unsatisfactory results. However, modern wound dressings offer promising approaches to surface reconstruction. Against the background of our future aim to develop an innovative skin substitute, we investigated the behavior of two established dermal substitutes, a crosslinked and a non-crosslinked collagen biomatrix. The products were applied topically on a total of 18 full-thickness skin defects paravertebrally on the back of female Göttingen Minipigs—six control wounds remained untreated. The evaluation was carried out planimetrically (wound closure time) and histologically (neoepidermal cell number and epidermis thickness). Both treatment groups demonstrated significantly faster reepithelialization than the controls. The histologic examination verified the highest epidermal thickness in the crosslinked biomatrix-treated wounds, whereas the non-crosslinked biomatrix-treated wounds showed a higher cell density. Our data presented a positive influence on epidermal regeneration with the chosen dermis substitutes even without additional skin transplantation and, thus, without additional donor site morbidity. Therefore, it can be stated that the single biomatrix application might be used in a clinical routine with small wounds, which needs to be investigated further in a clinical setting to determine the size and depths of a suitable wound bed. Nevertheless, currently available products cannot solely achieve wound healing that is equal to or superior to autologous tissue. Thus, the overarching aim still is the development of an innovative skin substitute to manage surface reconstruction without additional skin grafting.

Synergistic effect of photobiomodulation and phthalocyanine photosensitizer on fibroblast signaling responses in an in vitro three-dimensional microenvironment.

Photobiomodulation (PBM) is a promising medical treatment modality in the area of photodynamic therapy (PDT). In this study, we investigated the effect of combined therapy in a 3D microenvironment using aluminum chloride phthalocyanines (AlClPc) as the photosensitizing agent. Normal human fibroblast-containing collagen biomatrix was prepared and treated with an oil-in-water (o/a) AlClPc-loaded nanoemulsion (from 0.5 to 3.0μM) and irradiated at a range of fluences (from 0.1 to 3.0J/cm2) using a continuous-wave light-emitting diode (LED) irradiation system (660nm). PBM at 1.2J/cm2 and AlClPc/NE at 0.5μM modified the fibroblast signaling response under 3D conditions, promoting collagen synthesis, ROS production, MMP-9 secretion, proliferation of the actin network, and facile myofibroblastic differentiation. PBM alone (at 1.2J/cm2 and 0.3J/cm2) had no significant effect on any of these parameters. The combined therapy affected myofibroblastic differentiation, inflammatory response, and extracellular matrix pliability, and should thus be examined further in subsequent studies considering that no side effects of PBM have been reported. Even though significant progress has been made in the field of phototherapy in recent years, it is necessary to further elucidate the detailed mechanisms underlying its effects already shown in 2D conditions to increase the acceptance of this beneficial and non-invasive therapeutic approach.

Organotypic & in vitro monolayer modeling of urothelial carcinoma gives different cellular responses to proteinase activated receptor (PAR) agonism/antagonism

We hypothesized that microenvironment proteases generated by urothelial carcinoma (UC) cells dictate cell invasion & metastasis by signaling via Proteinase-Activated Receptors (PARs) and evaluated this hypothesis in UC cell lines in in vitro monolayer & organotypic 3D cultures UC cell lines: RT4, SW780, T24, 5637 In vitro: PAR1/2 function was assessed via calcium signalling assays. 2 methods detected UC-secreted proteases that cleave PAR1/2: 1) N-luciferase tag fused to PAR1/2 in a non-UC cell line released upon cleavage (paracrine proteinase activity); 2) N-terminal mCherry/RFP;C-terminal eYFP-tagged PAR construct transfected into UC cells to visualize receptor autocrine cleavage (intact receptor=yellow; cleaved receptor=green). The PAR1/2 effect on UC cell migration & invasion was assessed in monolayer wound healing assays with & without PAR1/2 agonism. Organotypic Model: UC cells were cultured in a bladder-derived fibroblast-containing 3D collagen biomatrix model that maintains epithelial phenotype & supports the growth of UC cell lines. UC cells were evaluated for proliferation, apoptosis, differentiation, & invasion in this model with/without PAR activation/inhibition. UC cell lines express PAR1/2 & secrete proteases & protease inhibitors that induce &/or affect signaling. PAR1/2 activating peptides stimulated migration & invasion of UC cells in monolayer cultures with inhibition by a PAR1 antagonist. In the organotypic setting neither PAR1 or 2 agonism caused significant proliferation, apoptosis, or invasion. Uniquely in the organotypic model we observed induction of differentiation in non-invasive cells (SW780 & RT4) & increased cytokeratin CK5-6 expression switching in the cell lines induced by PAR1 agonism & antagonism. Functional PAR1/2 are expressed by UC cells. Activation of these receptors increases invasion & migration in monolayer cultures, but not in organotypic cultures. Our data illustrate significant differences between monolayer & organotypic cultures & suggest PAR1 impacts cytokeratin expression & UC cell differentiation.

Bladder augmentation using acellular collagen biomatrix: a pilot experience in exstrophic patients

A preliminary experience on in vivo bladder wall regeneration in a subset of patients born with exstrophy-epispadias complex is reported. The objective was to improve bladder capacity and compliance without bowel augmentation. Five patients (3 males, 2 females), mean age 10.4 years, presenting poor bladder capacity and compliance after complete exstrophy repair, underwent bladder augmentation using small intestinal submucosa (SIS) scaffold. Ultrasonography, cystoscopy with cystogram, assessment of bladder volume and compliance and bladder biopsy were performed before surgery (T0), at 6 (T1) and 18 months (T2) follow-up. Histology was compared with normal bladder specimens. Wilcoxon test was adopted for statistics. Bladder capacity and compliance resulted increased (+30%) at T1 (p < 0.05) and remained stable at T2, despite dry intervals did not changed significantly. Bladder biopsy at T1 showed no evidence of SIS, but normal transitional mucosa and sero-muscular layer containing smooth muscle fascicles, small nerve trunks and vessels within abundant type-3 collagen. Muscle/collagen ratio was decreased compared with controls at T1 and T2 (p < 0.05). No kidney damage, bladder diverticula, or stones were observed at 3 years follow-up. Bladder regeneration was feasible in these patients, but bladder capacity and compliance was poorly increased to obtain significant clinical benefit. Histology showed poor muscle components. The acellular matrix grafting failed to provide long-term effective results in terms of continence achievement.

Use of a collagen biomatrix (TissuDura®) for dura repair: a long-term neuroradiological and neuropathological evaluation

The aim of this study was to evaluate the clinical, neuroradiological, and neuropathological outcomes of patients treated with equine collagen foil (TissuDura) as a dura mater substitute during cranial and spinal neurosurgical procedures. All patients treated at the Department of Neurosurgery of the Second University of Naples with TissuDura between 2005 and 2009 were included. Dural reconstruction was performed using TissuDura, overlaid 1 cm over the dural defect with additional fixation using fibrin glue. No surgical sutures were used. Patients underwent postoperative contrast-enhanced magnetic resonance scans at 1 week, 1 month, and 1 year after surgery to detect any cerebrospinal fluid (CSF) leaks, infections, inflammations, or CSF circulation in the surgical region. Dural reconstruction was performed in 74 patients, including 50 patients with tumors, two with C2 neurinoma, two with acoustic neurinoma, six with Chiari I malformation, two with severe head injury, and 12 requiring spinal surgery. Clinical and neuroradiological findings were normal and no signs of graft rejection or CSF leaks at postoperative follow-up were observed. In two cases of atypical meningioma, re-operation of the dural reconstruction was performed after 1 year. No adherences between brain and neodura were detected, and histopathological investigations demonstrated dural regeneration. Following dural reconstructions with TissuDura without surgical sutures, no local toxicity or complications were observed for up to 1 year. TissuDura demonstrated elasticity, non-reactivity, and good adaptability. The overlay technique using fibrin glue was simple and fast. Future studies and longer follow-up are needed to confirm the efficacy of TissuDura.

252 BLADDER TISSUE REGENERATION WITH A COLLAGEN-BASED BIOMATRIX IN A MODEL FOR BLADDER EXSTROPHY COMPARED TO REGENERATION IN NORMAL BLADDER

Purpose Patients with bladder exstrophy may need a bladder augmentation to improve function. Tissue engineering aims to develop alternatives for the current technique in which intestinal tissue is used. In this study we compared the regeneration of bladder tissue with a collagen-based biomatrix in a sheep model for bladder exstrophy with bladder tissue regeneration in normal bladder. Material and Methods Biomatrices of bovine collagen type I were prepared by subsequent freezing, lyophilisation and crosslinking. In 12 fetal sheep a bladder exstrophy was surgically created at 79 days’ gestation. Lambs were born at full term (140 days' gestation) by normal delivery. After one week the bladder lesion was reconstructed with a collagen biomatrix (group 1). In 10 normal newborn lambs the bladder was opened one week after birth, and closed with a collagen biomatrix (group 2). Functional (cystogram and urodynamic) and histological studies were performed to evaluate the bladders at 1 or 6 months after surgery. Results Survival rate was 58% in group 1 and 90% in group 2. In all animals the cystograms were normal, except for low grade reflux in some lambs of group 1. Urodynamic studies at 6 months showed lower compliance in group 1 (2.0 ± 1.4 versus 4.0 ± 2.7 ml/cmH2O). Histological evaluation at 1 month revealed small areas of squamous differentiation of regenerated urothelium in group 1. At 6 months in both groups normal urothelial lining was present, extracellular matrix was comparable, and slight smooth muscle cell ingrowth was seen. Conclusions This study indicates that bladder regeneration with a collagen-based biomatrix in diseased bladders results in functional bladder tissue with comparable characteristics as normal regenerated bladder tissue. This collagen-based biomatrix might be useful in reconstruction of bladder defects.

Bladder Tissue Regeneration with a Collagen-Based Biomatrix in a Model for Bladder Exstrophy Compared to Regeneration in Normal Bladder

Purpose Patients with bladder exstrophy may need a bladder augmentation to improve function. Tissue engineering aims to develop alternatives for the current technique in which intestinal tissue is used. In this study we compared the regeneration of bladder tissue with a collagen-based biomatrix in a sheep model for bladder exstrophy with bladder tissue regeneration in normal bladder. Material and Methods Biomatrices of bovine collagen type I were prepared by subsequent freezing, lyophilisation and crosslinking. In 12 fetal sheep a bladder exstrophy was surgically created at 79 days’ gestation. Lambs were born at full term (140 days' gestation) by normal delivery. After one week the bladder lesion was reconstructed with a collagen biomatrix (group 1). In 10 normal newborn lambs the bladder was opened one week after birth, and closed with a collagen biomatrix (group 2). Functional (cystogram and urodynamic) and histological studies were performed to evaluate the bladders at 1 or 6 months after surgery. Results Survival rate was 58% in group 1 and 90% in group 2. In all animals the cystograms were normal, except for low grade reflux in some lambs of group 1. Urodynamic studies at 6 months showed lower compliance in group 1 (2.0 ± 1.4 versus 4.0 ± 2.7 ml/cmH2O). Histological evaluation at 1 month revealed small areas of squamous differentiation of regenerated urothelium in group 1. At 6 months in both groups normal urothelial lining was present, extracellular matrix was comparable, and slight smooth muscle cell ingrowth was seen. Conclusions This study indicates that bladder regeneration with a collagen-based biomatrix in diseased bladders results in functional bladder tissue with comparable characteristics as normal regenerated bladder tissue. This collagen-based biomatrix might be useful in reconstruction of bladder defects.

Coverage of Fetal Skin Defects With a Collagen Biomatrix Loaded With Growth Factors in a Sheep Model

Purpose Patients with spina bifida suffer from severe morbidity. In former animal studies we have shown that coverage of a surgically created spina bifida during the fetal period can result in decreased morbidity after birth: less incontinence and less paralysis of the hindlimbs.1 However, to enhance skin regeneration, i.e. more angiogenesis and cell attraction, the biomatrix needs to be improved. Aim of this study is to evaluate the coverage of fetal skin defects with a collagen biomatrix, a biomatrix loaded with heparin and growth factors (VEGF and FGF) and wound healing without a biomatrix. Material and Methods At 79 days' gestation, 3 skin defects (O 10 mm) were created on the back of 11 fetal lambs. One defect was left uncovered, one was covered with a collagen biomatrix, and one with a biomatrix loaded with glycosaminoglycans (heparin) and growth factors (VEGF and FGF-2). Lambs were sacrificed at 93 (n = 4), 107 (n = 3) and 138 (n = 4) days' gestation. The skin defects were macroscopically and histologically examined. Results Macroscopic evaluation revealed wound healing mainly by wound contraction for the uncovered defects. The covered defect with plain biomatrix showed partially contraction and the covered defect with growth factor loaded biomatrix showed minor contraction. Histological evaluation revealed increased angiogenesis and keratinocyt growth in the growth-factor-loaded biomatrix. Additionally, decreased degradation of the biomatrix was seen in these defects, i.e. at 138 days' gestation the biomatrix was still largely present. Overall, improved maturation of skin tissue was seen in time. Conclusions Coverage of fetal skin defects with a VEGF and FGF-2 loaded collagen biomatrix resulted in less wound contraction, increased angiogenesis and keratinocyt growth. This biomatrix can be useful in coverage of large spina bifida defects to improve neonatal outcome. 1:Eggink et al. Fetal Diagnosis and Therapy 2005 Sep-Oct;20(5):335-40.

Collagen-Based Biomatrix with Growth Factors for Postnatal Repair in a Sheep Model with Bladder Exstrophy

Purpose Bladder exstrophy comes with extensive reconstructive surgery. Replacement of the currently used techniques by biomatrices might improve the final functional outcome. In this study we used a growth factor enriched collagen-based biomatrix to enhance bladder regeneration in a sheep model with bladder exstrophy. Material and Methods Biomatrices were prepared and crosslinked to increase structural integrity and to incorporate heparin. Heparin was used to specifically bind heparin binding growth factors (VEGF, FGF-2 and EGF) to induce bioactivity. In 12 fetal sheep a bladder exstrophy was prepared at 79 days' gestation. Lambs were born at 140 days' gestation with normal delivery. Bladder defect was reconstructed with plain collagen biomatrix (group 1) or a growth factor enriched biomatrix (group 2). Lambs were evaluated 1 or 6 months after surgery with contrast cystogram, urodynamic assessment and histology. Results After birth all bladder defects (n = 12) were open and reconstruction was performed. One lamb died during delivery. For all groups the cystogramic images were close to normal. After 6 months, the engineered bladders were more compliant and had greater capacity than those closed with the plain collagen biomatrix. Histological evaluation revealed increased angiogenesis and urothelial cell growth in the growth factor loaded biomatrix. Overall, improved maturation of bladder tissue was seen in time. Conclusions Coverage of bladder defects with a VEGF and FGF-2 loaded collagen biomatrix resulted in less wound contraction, increased angiogenesis and urothelial lining. The growth factor enriched biomatrix can be useful in repair and regeneration of bladder and cloacal exstrophies to improve neonatal outcome.

Transparent equine collagen biomatrix as dural repair. A prospective clinical study

Numerous materials have been used to replace defects in the dura mater as result of neurosurgical and spinal procedures. Tissudura is a biomatrix made of cross-linked equine collagen fibrils, mainly of the interstitial type I. The specially engineered dura-like layered structure provides a non porous primary water tight structure, is transparent and allows verification of the efficacy of cerebral hemostasis. A consecutive series of patients between 18 years and 75 years of age were prospectively enrolled from three separate European institutions between May 2007 and February 2008. All patients underwent elective cranial or spinal surgery and required implantation of a dural substitute. We assessed the efficacy and safety of the collagen biomatrix as a dural substitute, intraoperatively and postoperatively, with a median follow-up 4.3 months. Fifty-six patients had cranial surgery, four patients underwent a spinal operation. Surgical cranial approaches included supratentorial procedures in 45 patients and posterior cranial fossa exploration in 11. At 7-days follow-up, a CSF leak was reported in one patient after excision of a vestibular schwannoma and in another with a thoracic vertebral body fracture and spinal cord transaction. Neither needed reoperation. A subgaleal fluid collection in two patients who had been treated for a supratentorial lesion resolved after tapping. The transparency of the implant was beneficial to inspect the underlying surgical area at the end of the procedure in one patient in whom a hematoma formed after secondary to oozing glioblastoma removal. Of the 56 patients who reached the 3-month follow-up, none had a CSF leak, meningitis, wound infection or fistulae. No duroplasty failure was observed. In one patient who underwent reoperation after 40 days, histopathological findings revealed the replacement of the implant by ingrowth from the original dura. Tissudura is simple, efficacious and safe to use. The use of fibrin glue reduces suturing and facilitates the implantation of the collagen biomatrix. Its transparency makes it unique and beneficial in inspection of the underlying area of operation. The lack of adverse reaction indicates that this graft may be used as an option in the repair of dural defects.

Rabbit Urethra Replacement With a Molecularly-Defined Tubular Type I Collagen Biomatrix

Purpose The evaluation of a tubular molecularly-defined type I collagen biomatrix for replacement of the urethra in a rabbit model as a preclinical model. Material and Methods Highly purified type I collagen was obtained according to protocol. Tubular collagen biomatrices (O 3 mm) were prepared by lyophilization and strengthened by chemical crosslinking. Sixteen rabbits underwent tubular urethral replacement (resection of 1.0 cm segment of the urethra) which was replaced with the tubular biomatrix. The grafts of regenerated urethras were harvested at 2 weeks, 1, 3 and 6 months after surgery. Retrograde urethrography was performed in all rabbits before sacrifice. Then, the total penis of the rabbit was excised for histopathological examination. Results Biomatrices were biochemically analyzed and crosslinking was successful. No animals died before sacrifice. No strictures or urethrocutaneous fistula were observed on control urethrography. All animals showed no stenosis or loss of calibre at the biomatrix's position. There was relative anastomotic narrowing of the urethra in one rabbit at 2 weeks. Two rabbits had small diverticula at 3 months. Macroscopically, no infectious tissue was harvested. Currently, histological analysis is ongoing. Conclusions The tubular molecularly-defined biomatrices are successful in repairing urethral lesions. The results with our tubular biochemically defined biomatrix are promising, but remain to be confirmed by histological evaluation. Futurewise, the use of longer tubular segments and the addition of growth factors to biomatrices may be investigated.

Rabbit Urethra Replacement With a Molecularly-Defined Tubular Type I Collagen Biomatrix

Purpose The evaluation of a tubular molecularly-defined type I collagen biomatrix for replacement of the urethra in a rabbit model as a preclinical model. Material and Methods Highly purified type I collagen was obtained according to protocol. Tubular collagen biomatrices (Ø 3 mm) were prepared by lyophilization and strengthened by chemical crosslinking. Sixteen rabbits underwent tubular urethral replacement (resection of 1.0 cm segment of the urethra) which was replaced with the tubular biomatrix. The grafts of regenerated urethras were harvested at 2 weeks, 1, 3 and 6 months after surgery. Retrograde urethrography was performed in all rabbits before sacrifice. Then, the total penis of the rabbit was excised for histopathological examination. Results Biomatrices were biochemically analyzed and crosslinking was successful. No animals died before sacrifice. No strictures or urethrocutaneous fistula were observed on control urethrography. All animals showed no stenosis or loss of calibre at the biomatrix's position. There was relative anastomotic narrowing of the urethra in one rabbit at 2 weeks. Two rabbits had small diverticula at 3 months. Macroscopically, no infectious tissue was harvested. Currently, histological analysis is ongoing. Conclusions The tubular molecularly-defined biomatrices are successful in repairing urethral lesions. The results with our tubular biochemically defined biomatrix are promising, but remain to be confirmed by histological evaluation. Futurewise, the use of longer tubular segments and the addition of growth factors to biomatrices may be investigated. The evaluation of a tubular molecularly-defined type I collagen biomatrix for replacement of the urethra in a rabbit model as a preclinical model. Highly purified type I collagen was obtained according to protocol. Tubular collagen biomatrices (Ø 3 mm) were prepared by lyophilization and strengthened by chemical crosslinking. Sixteen rabbits underwent tubular urethral replacement (resection of 1.0 cm segment of the urethra) which was replaced with the tubular biomatrix. The grafts of regenerated urethras were harvested at 2 weeks, 1, 3 and 6 months after surgery. Retrograde urethrography was performed in all rabbits before sacrifice. Then, the total penis of the rabbit was excised for histopathological examination. Biomatrices were biochemically analyzed and crosslinking was successful. No animals died before sacrifice. No strictures or urethrocutaneous fistula were observed on control urethrography. All animals showed no stenosis or loss of calibre at the biomatrix's position. There was relative anastomotic narrowing of the urethra in one rabbit at 2 weeks. Two rabbits had small diverticula at 3 months. Macroscopically, no infectious tissue was harvested. Currently, histological analysis is ongoing. The tubular molecularly-defined biomatrices are successful in repairing urethral lesions. The results with our tubular biochemically defined biomatrix are promising, but remain to be confirmed by histological evaluation. Futurewise, the use of longer tubular segments and the addition of growth factors to biomatrices may be investigated.

Comparison of collagen biomatrix and omentum effectiveness on peripheral nerve regeneration

Despite the presence of various nerve coaptation materials and techniques, achievement of the functional nerve regeneration is still inadequate. This study was aimed to compare the effectiveness of conduit composed of collagen biomatrix and omentum graft on peripheral nerve regeneration. Thirty-five male Wistar rats were divided into four groups. In the control group, the right sciatic nerve was skeletonized from the sciatic notch till the point of bifurcation. In the primary epineural repair group, the nerve was transected 1 cm proximal to the bifurcation with a sharp pair of micro scissors and then repaired with four epineural sutures. In the collagen biomatrix group, the epineural repaired nerve was wrapped with collagen biomatrix. In the collagen group, the epineural repaired nerve was wrapped with the nonpediculated omentum. Assessment of the nerve regeneration was based on functional (Walking Track Analysis, Electrophysiological Measurements), histological, and morphometric criteria. Light and electron microscopic examinations showed that collagen-biomatrix-wrapped specimens have the best regeneration. The electrophysiological study confirmed the recovery of electrical activity in the regenerated axons.