A bioabsorbable mechanoelectric fiber as electrical stimulation suture.

In surgical medicine, suturing is the standard treatment for large incisions, yet traditional sutures are limited in functionality. Electrical stimulation is a non-pharmacological therapy that promotes wound healing. In this context, we designed a passive and biodegradable mechanoelectric suture. The suture consists of multi-layer coaxial structure composed of (poly(lactic-co-glycolic acid), polycaprolactone) and magnesium to allow safe degradation. In addition to the excellent mechanical properties, the mechanoelectrical nature of the suture grants the generation of electric fields in response to movement and stretching. This is shown to speed up wound healing by 50% and reduce the risk of infection. This work presents an evolution of the conventional wound closure procedures, using a safe and degradable device ready to be translated into clinical practice.

Bone into Bone technique: An alternative to horizontal bone regeneration techniques. Retrospective case-control study.

PURPOSE: To evaluate the efficacy of lateral ridge augmentation (LRA) of porcine cortical barriers when placed in a surgical bone gap, buccal to the defect, using the Bone into Bone (BiB) technique compared to a guided bone regeneration (GBR) technique. METHODS: The study was a retrospective case-control evaluation. A group of 23 subjects (test) underwent horizontal augmentation procedures using the BiB technique. A group of 18 subjects (control) was treated with the guided bone regeneration (GBR) technique, using a resorbable membrane and a mixture of heterologous bovine particles and autologous bone fragments. Radiological and histological analysis of the outcomes were performed. RESULTS: Mean ridge width varied from a preoperative value of 3.4 mm to a postoperative value, measured 8 months postoperatively, of 7.1 mm in the Control Group. The mean ridge width varied from a preoperative value of 4.8 mm to a postoperative value, measured 8 months after the procedure, of 7.5 mm in the Test Group. Histological images, after 8 months, showed native, mineralized bone with a lamellar pattern of varying thickness (30.3% ± 5.3). CLINICAL SIGNIFICANCE: This technique (Bone-into-Bone) using resorbable heterologous biomaterials and without the use of retention devices for horizontal bone augmentation may be a viable alternative that is easily reproducible and has reduced morbidity for the patient.

Closure of small oroantral communications using heterologous biomaterials: A case series.

PURPOSE: To provide a surgical strategy for small oroantral communication closure and bone regeneration that can meet the needs of an effective, less invasive, and simpler operation by utilizing procedures and biomaterials commonly employed in guided bone regeneration techniques. The primary goal was to close the communication, while the second aim was to achieve bone regeneration. METHODS: This retrospective and monocentric case series was conducted using data from the medical records of 12 subjects with oroantral communications and bone deficits greater than 3 mm who were treated with a heterologous cortico-cancellous graft covered in resorbable collagen membranes. The primary outcome was communication closure, whereas the secondary outcome was bone augmentation, which was demonstrated radiographically and clinically. RESULTS: Twelve individuals were treated consecutively for oroantral communication closure. The subjects consisted of eight men and four women. The mean age was 57.5 years. Closure was effective in all 12 subjects, and radiographic examination after 6 months revealed bone reformation in all cases. This procedure effectively isolated the maxillary sinus from the mouth cavity, resulting in seal and healing, as well as bone regeneration. CLINICAL SIGNIFICANCE: Small oroantral communications are frequent in dentistry, often requiring special expertise and interventions that affect patient morbidity. The use of a heterologous cortico-cancellous graft covered with resorbable collagen membranes can allow effective closure of the small communication, preventing migration of pathological epithelia while increasing the bone ridge.

Bone augmentation using bioresorbable mesh domes containing bone graft granules.

Bone graft granules are valuable tools for ridge area bone grafting owing to their ease of manipulation and interconnected porous structure. Guided bone regeneration (GBR) using barrier membranes is commonly used for alveolar ridge augmentation; however, the surgical procedures are technically complicated. In this study, we fabricated bioresorbable mesh domes (BMDs) using two types of Vicryl mesh (woven and knitted types) containing carbonate apatite granules. BMD samples were prepared in three groups: upper sides made from the woven type (UW) and lower sides made from the woven type (LW) (the UW/LW group), upper sides made from the woven type (UW) and lower sides made from the knitted type (LK) (the UW/LK group), and upper sides made from the knitted type (UK) and lower sides made from the knitted type (LK) (the UK/LK group). The samples were subsequently implanted into rabbit calvaria, and radiomorphometric and histological analyses were conducted. The UK/LK group exhibited enhanced appositional bone formation because the knitted mesh on the skin side prevented the infiltration of a substantial amount of fibrous tissue. This increase in bone formation could be attributed to the interaction between granules and osteoprogenitors that pass through the mesh from the host bone. Conversely, the UW/LW and UW/LK groups presented limited appositional bone formation. Compared with knitted mesh, woven mesh might tend to be absorbed over a short span, allowing fibrous tissue invasion and inhibiting new bone formation. Additionally, BMDs could retain granules in a targeted location and avoid displacement of the granules to unintended locations.

Animal Experimental Study of Bioabsorbable Left Atrial Appendage Occluder.

Left atrial appendage (LAA) closure can prevent stroke in high-risk patients with atrial fibrillation.A bioabsorbable LAA occluder made of degradable polymer materials, such as polydioxanone (PDO) and poly-L-lactic acid (PLA), and nitinol wire was used. Occluders were successfully implanted in 18 Chinese rural dogs, 2 of which died within 48 hours after operation due to pericardial tamponade and hemorrhage, respectively. Follow-up observation was performed after transcatheter LAA closure. New tissue was found on the surface of the occluder 2 months after operation. No adjacent structures such as the mitral valve and the left superior pulmonary vein were affected by the occluder discs. Hematoxylin and eosin (HE) staining was performed at 3 months after operation, which showed intact intimal structure on the occluder surface, and unabsorbed PDO and PLA were observed. Scanning electron microscopy showed irregular arrangement of endothelial cells. New endothelial tissue was observed to completely cover the occluder at 6 months after operation. Most PDOs were replaced by fibrous connective tissue, and scanning electron microscopy showed regularly arranged endothelial cells. Pathological examination at 12 months showed only a small remnant of PDO. The gross specimens of the liver, spleen, and kidneys and pathological examination did not indicate thromboembolism.The bioabsorbable LAA occluder made of PDO, PLA, and nitinol wire was safe and effective for the occlusion of LAA in dogs. The surface of the occluder was endothelialized half a year after operation. The absorbable materials of the occluder were degraded after 1 year.

Comparison of biodegradable and metallic tension-band fixation for paediatric lateral condyle fracture of the elbow.

INTRODUCTION: In our retrospective study we compared the outcomes of paediatric lateral condyle fractures of the elbow fixed by bioabsorbable pins and tension-band sutures or by metallic tension-band with K-wires. MATERIALS AND METHODS: We reviewed the data of children operated on for lateral condyle fractures between 2010 and 2020. Patients were classified as follows: 1. fractures treated with metallic (KW group), 2. fractures treated with resorbable implants (BR group). We compared the distribution of age, sex and fracture type in each group. Operative times of the two techniques were also recorded and compared. We analysed the X-rays taken one year after the injury and measured the following parameters: presence of possible non-union, varus or valgus deviation, lateral spur formation. Patients whose follow-up period was less than one year were excluded. For categorical data, group comparisons were performed with Chi-square test or Fisher's exact test, depending on the sample size. The evaluation of discrete variables was performed with Mann-Whitney U test. RESULTS: 42 patients met the above criteria. We found 19 children in the Kirschner -wire + tansion band wire (KW) group and 23 in the Bioresorbable pin + tension band suture (BR) group. There were no significant differences between the study groups in terms of age, sex, left-right ratio, number of complications, operation time, number of Jacobs II and III cases or follow-up time. The operation time was on average 5 min longer in the bioresorbable group (K-wire mean = 62.1 min, Bioresorbable mean = 67 min), this difference, however, is not statistically significant (P = 0.177). In terms of minor and major complications, there was no statistically significant difference between the two groups. (P = 0.729). CONCLUSIONS: We did not notice any difference between the complication rates of the two methods, so the real advantage of the absorbable implant technique is that no second intervention is necessary. The benefits of using biodegradable implants in various osteosynthesis techniques need further confirmation by randomised trials.

Vascular response following implantation of the third-generation drug-eluting resorbable coronary magnesium scaffold: an intravascular imaging analysis of the BIOMAG-I first-in-human study.

BACKGROUND: The 12-month outcomes of BIOMAG-I - the first-in-human study investigating the third-generation drug-eluting resorbable magnesium scaffold (DREAMS 3G) - showed promising results regarding clinical outcomes and late lumen loss. AIMS: The current study aimed to investigate vascular healing parameters assessed by optical coherence tomography (OCT) and intravascular ultrasound (IVUS), focusing on strut visibility, vessel and scaffold areas, and neointimal growth patterns. METHODS: This is a BIOMAG-I substudy including patients with available serial OCT and IVUS data. We conducted a frame-based analysis of OCT findings in conjunction with IVUS-derived vessel and scaffold areas, evaluating the qualitative and quantitative aspects of vascular healing. RESULTS: Among the 116 patients enrolled in this trial, 56 patients treated with DREAMS 3G were included in the analysis. At 12 months, OCT imaging revealed that 99.0% of the struts were invisible, and no malapposed struts were depicted. While the vessel area showed no significant difference between the timepoints, the minimum lumen area significantly decreased from post-percutaneous coronary intervention to 6 months (6.88 mm2 to 4.75 mm2; p<0.0001), but no significant changes were observed between 6 and 12 months. Protruding neointimal tissue (PNT) - a unique neointimal presentation observed following resorbable magnesium scaffold implantation - was observed in 89.3% of the study patients at 12 months, and its area exhibited a 47.4% decrease from 6 to 12 months. CONCLUSIONS: This imaging substudy revealed that, at 12-month follow-up, virtually all struts of the DREAMS 3G scaffold became invisible, without evident malapposition. The vascular healing response to DREAMS 3G implantation also appeared favourable up to 12 months, which is indicated by advanced strut degradation and spontaneous regressing PNT between 6 and 12 months.

Maglev-fabricated long and biodegradable stent for interventional treatment of peripheral vessels.

While chronic limb-threatening ischemia is a serious peripheral artery disease, the lack of an appropriate stent significantly limits the potential of interventional treatment. In spite of much progress in coronary stents, little is towards peripheral stents, which are expected to be both long and biodegradable and thus require a breakthrough in core techniques. Herein, we develop a long and biodegradable stent with a length of up to 118 mm based on a metal-polymer composite material. To achieve a well-prepared homogeneous coating on a long stent during ultrasonic spraying, a magnetic levitation is employed. In vivo degradation of the stent is investigated in rabbit abdominal aorta/iliac arteries, and its preclinical safety is evaluated in canine infrapopliteal arteries. First-in-man implantation of the stent is carried out in the below-the-knee artery. The 13 months' follow-ups demonstrate the feasibility of the long and biodegradable stent in clinical applications.

Treatment of a urethral stricture by image-guided placement of a custom-made absorbable stent in a standing, sedated horse.

A 10-year-old Irish Sport Horse gelding developed complications from a general anesthesia resulting in sling support and recurrent urinary catheterization. The horse subsequently presented signs of dysuria and pollakiuria, was diagnosed with sabulous cystitis, and developed a urethral stricture from the repeated catheterizations, which was confirmed on urethroscopy. Clinical signs persisted despite conservative management with topical corticosteroids and urethral bougienage with balloon dilators. An image-guided approach was used to treat the stricture with a custom-made polydioxanone stent placed in the urethra after which the horse was able to void normally and fully empty his bladder. Repeat urethroscopy and ultrasonography 6 months after the procedure showed the stent to have completely reabsorbed with urethra remaining patent. Nineten months after the procedure, the owner reports the horse remaining at his intended level of athletic performance with no dysuria.

Nanoparticle-Enabled Zn-0.1Mg Alloy with Long-Term Stability, Refined Degradation, and Favorable Biocompatibility for Biodegradable Implant Devices.

Zinc-based alloys, specifically Zn-Mg, have garnered considerable attention as promising materials for biodegradable implants due to their favorable mechanical strength, appropriate corrosion rate, and biocompatibility. Nevertheless, the alloy's lack of mechanical stability and integrity, resulting from ductility loss induced by age hardening at room temperature, hampers its practical bioapplication. In this study, ceramic nanoparticles have been successfully incorporated into the Zn-Mg alloy system, leading to a significant improvement in long-term stability as well as mechanical strength and ductility. In addition, this study represents the first investigation of Zn-based nanocomposites both in vitro and in vivo to comprehend the influence of nanoparticles on the degradation behavior and biocompatibility of the Zn system. The findings indicate that the incorporation of WC nanoparticles effectively refines and stabilizes the degradation behavior of Zn-Mg without negatively impacting the cytocompatibility of the alloy. The subcutaneous implantation and femoral implantation further prove the benefits of nanoparticle incorporation and found no negative effects. Collectively, Zn-Mg-WC nanocomposites yield great potential for implant usage.

Five-year outcomes of patients with diabetes mellitus treated with a sirolimus-eluting or a biolimus-eluting stents with biodegradable polymer. From the SORT OUT VII trial.

BACKGROUND: Diabetes mellitus is associated with higher risk of target lesion failure (TLF) after percutaneous coronary intervention. We studied the 5-year outcome in patients with diabetes mellitus treated with biodegradable polymer stents. METHODS: The SORT OUT VII was a randomised trial comparing the ultrathin sirolimus-eluting Orsiro stent (O-SES) and the biolimus-eluting Nobori stent (N-BES) in an all-comer setting. Patients (n = 2525) were randomised to receive O-SES (n = 1261, diabetes: n = 236) or N-BES (n = 1264, diabetes: n = 235). Endpoints were TLF (a composite of cardiac death, target-lesion myocardial infarction (MI), target lesion revascularization (TLR)), definite stent thrombosis and a patient related outcome (all-cause mortality, MI and revascularization) within 5 years. RESULTS: Patients with diabetes mellitus had higher TLF (20.6% vs 11.0%, (Rate ratio (RR) 1.85 95% confidence interval (CI): (1.42-2.40) and patient related outcome (42.0% vs 31.0%, RR 1.43 95% CI: (1.19-1.71)) compared to patients without diabetes. Among patients with diabetes mellitus, TLF after 5 years did not differ between O-SES and N-BES (21.2% vs 20.0%), RR 1.05 95% CI: (0.70-1.58), p = 0.81). Cardiac death, MI, TLR, and definite stent thrombosis did not differ between the groups. CONCLUSION: In patients with diabetes mellitus, 5-year outcomes were similar among patients treated with biodegradable polymer O-SES or N-BES. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01879358.

Effect of hematoma on early degradation behavior of magnesium after implantation.

The corrosion of magnesium (Mg)-based bioabsorbable implanting devices is influenced by implantation environment which dynamically changes by biological response including wound healing. Understanding the corrosion mechanisms along the healing process is essential for the development of Mg-based devices. In this study, a hematoma model was created in a rat femur to analyze Mg corrosion with hematoma in the early stage of implantation. Pure Mg specimen (99.9%,ϕ1.2 × 6 mm) was implanted in rat femur under either hematoma or non-hematoma conditions. After a designated period of implantation, the specimens were collected and weighed. The insoluble salts formed on the specimen surfaces were analyzed using scanning electron microscopy, energy-dispersive x-ray spectroscopy, and Raman spectroscopy on days 1, 3, and 7. The results indicate that hematomas promote Mg corrosion and change the insoluble salt precipitation. The weight loss of the hematoma group (27.31 ± 5.91 µg mm-2) was significantly larger than that of the non-hematoma group (14.77 ± 3.28 µg mm-2) on day 7. In the non-hematoma group, carbonate and phosphate were detected even on day 1, but the only latter was detected on day 7. In the hematoma group, hydroxide was detected on day 1, followed by the formation of carbonate and phosphate on days 3 and 7. The obtained results suggest the hypoxic and acidic microenvironment in hematomas accelerates the Mg corrosion immediately after implantation, and the subsequent hematoma resorption process leads to the formation of phosphate and carbonate with organic molecules. This study revealed the risk of hematomas as an acceleration factor of the corrosion of Mg-based devices leading to the early implant failure. It is important to consider this risk in the design of Mg-based devices and to optimize surgical procedures controlling hemorrhage at implantation and reducing unexpected bleeding after surgery.

Gd Added Mg Alloy for Biodegradable Implant Applications.

Microstructure, mechanical, in vitro and in vivo behavior of extruded Mg alloys with varying Zn/Gd ratios, Mg-2Gd-2Zn-0.5Zr (Zn/Gd = 1), Mg-2Gd-6Zn-0.5Zr (Zn/Gd = 3), and Mg-10Gd-1Zn-0.5Zr (Zn/Gd = 0.1) were investigated. The results revealed that the major secondary phases such as W (Mg3Zn3Gd2), (Mg,Zn)3Gd, LPSO (Long period stacking order) and I (Mg3Zn6Gd) phase in alloys depended on Zn/Gd ratio. These second phases influenced the mechanical as well as biological characteristics of the alloys. Among studied alloys, Mg-10Gd-1Zn-0.5Zr alloy showed the highest yield strength and tensile strength of 270 (±9.29) and 330 MPa (±15.8), respectively, with a reasonably good elongation of 12% (±2.36). The presence of Gd2O3 in the degradation film of Mg-10Gd-1Zn-0.5Zr enhanced the resistance offered by the film, which resulted in its lowest biodegradation, better viability, and cell proliferation under in vitro condition. The short term (subcutaneous implantation in rats for 1 month) in vivo studies showed that the alloy Mg-10Gd-1Zn-0.5Zr degraded at a rate of 0.35 mm/y (±0.02) and did not induce any toxicity to the vital organs.

Bioabsorbable, subcutaneous naltrexone implants mitigate fentanyl-induced respiratory depression at 3 months-A pilot study in male canines.

The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly-d,l-Lactic Acid (PDLLA) and/or Polycaprolactone (PCL-1 or PCL-2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97-100 days after implantation. Following the administration of a 30 µg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre-dose respiratory rate (RR). The BIOPIN NTX-implanted dogs were exposed to escalating doses of intravenous fentanyl (30 µg/kg, 60 µg/kg, 90 µg/kg, and 120 µg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 µg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 µg/kg and especially at 120 µg/kg. Bioabsorbable, extended-release BIOPIN naltrexone implants are effective in mitigating fentanyl-induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl-induced respiratory depression in humans.

Rationale and design of INFINITY-SWEDEHEART: A registry-based randomized clinical trial comparing clinical outcomes of the sirolimus-eluting DynamX bioadaptor to the zotarolimus-eluting Resolute Onyx stent.

BACKGROUND: Modern drug-eluting stents have seen significant improvements, yet still create a rigid cage within the coronary artery. There is a 2% to 4% annual incidence of target lesion failure (TLF) beyond 1 year, and half of the patients experience angina after 5 years. The DynamX bioadaptor is a sirolimus-eluting, thin (71 µm) cobalt-chromium platform with helical strands that unlock and separate after in vivo degradation of the bioresorbable polymer coating. This allows the vessel to return to normal physiological function and motion, along with compensatory adaptive remodeling, which may reduce the need for reintervention and alleviate angina following percutaneous coronary intervention (PCI). METHODS: The INFINITY-SWEDEHEART trial is a single-blind, registry-based randomized clinical trial (R-RCT) to evaluate the safety and effectiveness of the DynamX bioadaptor compared to the Resolute Onyx stent in the treatment of patients with ischemic heart disease with de novo native coronary artery lesions. The R-RCT framework allows for recruitment, randomization, and pragmatic data collection of baseline demographics, medications, and clinical outcomes using existing national clinical registries integrated with the trial database. The primary objective is to demonstrate noninferiority in terms of freedom from TLF (cardiovascular death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year. Powered secondary endpoints will be tested sequentially for superiority from 6 months to the end of follow-up (5 years) for the following: 1) TLF in all subjects, 2) target vessel failure in all subjects, and 3) TLF in subjects with acute coronary syndrome (ACS). Subsequent superiority testing will be performed at a time determined depending on the number of events, ensuring sufficient statistical power. Change in angina-related symptoms, function and quality of life will be assessed using the Seattle Angina Questionnaire-short version. Predefined sub-groups will be analyzed. In total, 2400 patients have been randomized at 20 sites in Sweden. Available baseline characteristic reveal relatively old age (68 years) and a large proportion of ACS patients including 25% STEMI and 37% NSTEMI patients. SUMMARY: The INFINITY-SWEDEHEART study is designed to evaluate the long-term safety and efficacy of the DynamX bioadaptor compared to the Resolute Onyx stent in a general PCI patient population.

Biocompatibility and osteogenic capacity of additively manufactured biodegradable porous WE43 scaffolds: An in vivo study in a canine model.

Magnesium is the most promising absorbable metallic implant material for bone regeneration and alloy WE43 is already FDA approved for cardiovascular applications. This study investigates the cyto- and biocompatibility of novel additively manufactured (AM) porous WE43 scaffolds as well as their osteogenic potential and degradation characteristics in an orthotopic canine bone defect model. The cytocompatibility was demonstrated using modified ISO 10993-conform extract-based indirect and direct assays, respectively. Additionally, degradation rates of WE43 scaffolds were quantified in vitro prior to absorption tests in vivo. Complete blood cell counts, blood biomarker analyses, blood trace element analyses as well as multi-organ histopathology demonstrated excellent biocompatibility of porous y WE43 scaffolds for bone defect repair. Micro-CT analyses further showed a relatively higher absorption rate during the initial four weeks upon implantation (i.e., 36 % ± 19 %) than between four and 12 weeks (41 % ± 14 %), respectively. Of note, the porous WE43 implants were surrounded by newly formed bony tissue as early as four weeks after implantation when unmineralized trabecular ingrowth was detected. After 12 weeks, a substantial amount of mineralized bone was detected inside and around the gradually disappearing implants. This first study on AM porous WE43 implants in canine bone defects demonstrates the potential of this alloy for in vivo applications in humans. Our data further underscore the need to control initial bulk absorption kinetics through surface modifications.

Bioresorbable Scaffold Use in Coronary Chronic Total Occlusions: A Long-Term, Single-Center Follow-Up Study.

Background and Objectives: Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) is often associated with longer total stent length. Our aim was to evaluate the long-term safety and effectiveness of bioresorbable scaffold (BRS) implantation in CTO to avoid using a full metal jacket. Materials and Methods: We conducted a single-center prospective longitudinal case study including 34 patients who underwent PCI of CTO with at least one BRS and drug-eluting stent (DES) implantation (n = 27) or BRS-only at the Latvian Centre of Cardiology between 2016 and 2018. Quantitative coronary angiography (QCA) and intravascular ultrasound were performed during the index procedure and long-term follow-up. Results: Of 34 patients with a mean age of 60.6 ± 9.5 years, 76.5% were male. The most common CTO artery was the right coronary artery (73.5%, n = 25). The median length of occlusion was 23.0 mm (interquartile range (IQR) = 13.9-32.7), with a total mean BRS/DES length of 49.6 ± 20.4 mm. During the median follow-up of 5.6 years (IQR = 5.0-5.9), the primary endpoint of target vessel re-occlusion occurred in 5.9% (n = 2) of patients. Target lesion revascularization (TLR) was performed in 35.3% (n = 12) of patients, with a mean time to TLR of 62.5 (95% confidence interval (CI), 53.9-71.2) months. Through QCA, there was a statistically significant increase in median residual diameter stenosis (20.1-31.4%, p < 0.01) and residual length of stenosis (5.2-7.1%, p = 0.04) compared with the index procedure. Conclusions: Our study demonstrates that BRS is a safe and feasible option for PCI of CTO, allowing for the avoidance of long segment stenting and ensuring long-term patency of the coronary artery.