Recent Advances in the Degradability and Applications of Tissue Adhesives Based on Biodegradable Polymers.

In clinical practice, tissue adhesives have emerged as an alternative tool for wound treatments due to their advantages in ease of use, rapid application, less pain, and minimal tissue damage. Since most tissue adhesives are designed for internal use or wound treatments, the biodegradation of adhesives is important. To endow tissue adhesives with biodegradability, in the past few decades, various biodegradable polymers, either natural polymers (such as chitosan, hyaluronic acid, gelatin, chondroitin sulfate, starch, sodium alginate, glucans, pectin, functional proteins, and peptides) or synthetic polymers (such as poly(lactic acid), polyurethanes, polycaprolactone, and poly(lactic-co-glycolic acid)), have been utilized to develop novel biodegradable tissue adhesives. Incorporated biodegradable polymers are degraded in vivo with time under specific conditions, leading to the destruction of the structure and the further degradation of tissue adhesives. In this review, we first summarize the strategies of utilizing biodegradable polymers to develop tissue adhesives. Furthermore, we provide a symmetric overview of the biodegradable polymers used for tissue adhesives, with a specific focus on the degradability and applications of these tissue adhesives. Additionally, the challenges and perspectives of biodegradable polymer-based tissue adhesives are discussed. We expect that this review can provide new inspirations for the design of novel biodegradable tissue adhesives for biomedical applications.

The role of sealants for achieving anastomotic hemostasis in vascular surgery.

BACKGROUND: During vascular interventions, connections that link arteries, veins, or synthetic grafts, which are known as an 'anastomosis', may be necessary. Vascular anastomoses can bleed from the needle holes that result from the creation of the anastomoses. Various surgical options are available for achieving hemostasis, or the stopping of bleeding, including the application of sealants directly onto the bleeding vessels or tissues. Sealants are designed for use in vascular surgery as adjuncts when conventional interventions are ineffective and are applied directly by the surgeon to seal bleeding anastomoses. Despite the availability of several different types of sealants, the evidence for the clinical efficacy of these hemostatic adjuncts has not been definitively established in vascular surgery patients. OBJECTIVES: To evaluate the benefits and harms of sealants as adjuncts for achieving anastomotic site hemostasis in patients undergoing vascular surgery. SEARCH METHODS: The Cochrane Vascular Information Specialist conducted systematic searches of the following databases: the Cochrane Vascular Specialised Register via the Cochrane Register of Studies; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE via Ovid; Embase via Ovid ; and CINAHL via EBSCO. We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform for clinical trials. Reference lists of included trials and relevant reviews were also searched. The latest search date was 6 March 2023. SELECTION CRITERIA: We included randomized controlled trials that compared fibrin or synthetic sealant use with alternative interventions (e.g. manual compression, reversal of anticoagulation) for achieving anastomotic-site hemostasis in vascular surgery procedures. We included participants who underwent the creation of an anastomosis during vascular surgery. We excluded non-vascular surgery patients. DATA COLLECTION AND ANALYSIS: We have used standard Cochrane methods. Our primary outcomes were time to hemostasis, failure of hemostatic intervention, and intraoperative blood loss. Our secondary outcomes were operating time, death from bleeding complications up to 30 days, postoperative bleeding up to 30 days, unplanned return to the operating room for bleeding complications management up to 30 days, quality of life, and adverse events. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We found 24 randomized controlled trials that included a total of 2376 participants who met the inclusion criteria. All trials compared sealant use with standard care controls, including oxidized cellulose, gelatin sponge, and manual compression. All trials were at high risk of performance bias, detection bias, and other sources of bias. We downgraded the certainty of evidence for risk of bias concerns, inconsistency, imprecision and possible publication bias. Combining data on time to hemostasis showed that sealant use may reduce the mean time to hemostasis compared to control (mean difference (MD) -230.09 seconds, 95% confidence interval (CI) -329.24 to -130.94; P < 0.00001; 7 studies, 498 participants; low-certainty evidence). Combining data on failure of hemostatic intervention showed that sealant use may reduce the rate of failure compared to control, but the evidence is very uncertain (risk ratio (RR) 0.46, 95% CI 0.35 to 0.61; P < 0.00001; 17 studies, 2120 participants; very low-certainty evidence). We did not detect any clear differences between the sealant and control groups for intraoperative blood loss (MD -32.69 mL, 95% CI -96.21 to 30.83; P = 0.31; 3 studies, 266 participants; low-certainty evidence); operating time (MD -18.72 minutes, 95% CI -40.18 to 2.73; P = 0.09; 4 studies, 436 participants; low-certainty evidence); postoperative bleeding (RR 0.78, 95% CI 0.59 to 1.04; P = 0.09; 9 studies, 1216 participants; low-certainty evidence), or unplanned return to the operating room (RR 0.27, 95% CI 0.04 to 1.69; P = 0.16; 8 studies, 721 participants; low-certainty evidence). No studies reported death from bleeding or quality of life outcomes. AUTHORS' CONCLUSIONS: Based on meta-analysis of 24 trials with 2376 participants, our review demonstrated that sealant use for achieving anastomotic hemostasis in vascular surgery patients may result in reduced time to hemostasis, and may reduce rates of hemostatic intervention failure, although the evidence is very uncertain, when compared to standard controls. Our analysis showed there may be no differences in intraoperative blood loss, operating time, postoperative bleeding up to 30 days, and unplanned return to the operating room for bleeding complications up to 30 days. Deaths and quality of life could not be analyzed. Limitations include the risk of bias in all studies. Our review has demonstrated that using sealants may reduce the time required to achieve hemostasis and the rate of hemostatic failure. However, a significant risk of bias was identified in the included studies, and future trials are needed to provide unbiased data and address other considerations such as cost-effectiveness and adverse events with sealant use.

Treatment of gastric varices with cyanoacrylate complicated by systemic embolization.

Acute gastric variceal bleeding is a life-threatening condition that could be effectively treated with endoscopic cyanoacrylate injection diluted with lipiodol. The mixture acts as a tissue adhesive that polymerizes when in contact with blood in a gastric varix. This work reports a patient that presented to the emergency department with upper gastrointestinal bleeding due to acute variceal bleeding, who developed systemic embolization following cyanoacrylate injection therapy. This complication culminated in cerebral, splenic and renal infarctions with a fatal outcome. Systemic embolization is a very rare, but the most severe complication associated with endoscopic cyanoacrylate injection and should be considered in patients undergoing this treatment.

Glued suture-less peritoneum closure in laparoscopic inguinal hernia repair reduces acute postoperative pain.

Inguinal hernia repair is performed more than 20 million times per annum, representing a significant health and economic burden. Over the last three decades, significant technical advances have started to reduce the invasiveness of these surgeries, which translated to better recovery and reduced costs. Here we bring forward an innovative surgical technique using a biodegradable cyanoacrylate glue instead of a traumatic suture to close the peritoneum, which is a highly innervated tissue layer, at the end of endoscopy hernia surgery. To test how this affects the invasiveness of hernia surgery, we conducted a cohort study. A total of 183 patients that underwent minimally invasive hernia repair, and the peritoneum was closed with either a conventional traumatic suture (n = 126, 68.9%) or our innovative approach using glue (n = 57, 31.1%). The proportion of patients experiencing acute pain after surgery was significantly reduced (36.8 vs. 54.0%, p = 0.032) by using glue instead of a suture. In accordance, the mean pain level was higher in the suture group (VAS = 1.5 vs. 1.3, p = 0.029) and more patients were still using painkillers (77.9 vs. 52.4%, p = 0.023). Furthermore, the rate of complications was not increased in the glue group. Using multivariate regressions, we identified that using a traumatic suture was an independent predictor of acute postoperative pain (OR 2.0, 95% CI 1.1-3.9, p = 0.042). In conclusion, suture-less glue closure of the peritoneum is innovative, safe, less painful, and possibly leads to enhanced recovery and decreased health costs.

Hemopatch® as a primary dural sealant in cranial neurosurgery: Technical note and a retrospective study.

OBJECTIVES: To determine the effectiveness and safety of Hemopatch® as a primary dural sealant in preventing CSF leakage following cranial surgery. Cerebrospinal fluid (CSF) leaks occur in cranial operations and are associated with significant patient burden and expense. The use of Hemopatch® as a dural sealant in cranial neurosurgical procedures is described and analyzed in this study. METHODS: Data were retrospectively collected from all patients who underwent a craniotomy for various neurosurgical indications where Hemopatch® was used as the primary dural sealant between June 2017 and June 2022. Infection and CSF leak were the main indicators evaluated after surgery. RESULTS: A total of 119 consecutive patients met our inclusion criteria. The median was age 41.5 years, and 52.5% were female. The mean follow-up period was 2.3 years (7 months to 6 years). There were 110 (92.44%) supratentorial and 9 (7.56%) infratentorial craniotomies. Postoperative CSF leak was reported in 2 patients (1.68%), one in each cohort. Postoperative infection occurred in one patient (0.84%). CONCLUSION: The results suggest that using Hemopatch® as a dural sealant in cranial surgery is effective and safe. After supra-/infratentorial craniotomies, the rate of postoperative adverse events in our sample was within the range of known surgical revision rates. Future randomized clinical studies are required to confirm our encouraging findings.

Tensile strength of adhesives in peripheral nerve anastomoses: an in vitro biomechanical evaluation of four different neurorrhaphies.

BACKGROUND: The fundamental prerequisite for prognostically favorable postoperative results of peripheral nerve repair is stable neurorrhaphy without interruption and gap formation. METHODS: This study evaluates 60 neurorrhaphies on femoral chicken nerves in terms of the procedure and the biomechanical properties. Sutured neurorrhaphies (n = 15) served as control and three sutureless adhesive-based nerve repair techniques: Fibrin glue (n = 15), Histoacryl glue (n = 15), and the novel polyurethane adhesive VIVO (n = 15). Tensile and elongation tests of neurorrhaphies were performed on a tensile testing machine at a displacement rate of 20 mm/min until failure. The maximum tensile force and elongation were recorded. RESULTS: All adhesive-based neurorrhaphies were significant faster in preparation compared to sutured anastomoses (p < 0.001). Neurorrhaphies by sutured (102.8 [cN]; p < 0.001), Histoacryl (91.5 [cN]; p < 0.001) and VIVO (45.47 [cN]; p < 0.05) withstood significant higher longitudinal tensile forces compared to fibrin glue (10.55 [cN]). VIVO, with △L/L0 of 6.96 [%], showed significantly higher elongation (p < 0.001) compared to neurorrhaphy using fibrin glue. CONCLUSION: Within the limitations of an in vitro study the adhesive-based neurorrhaphy technique with VIVO and Histoacryl have the biomechanical potential to offer alternatives to sutured neuroanastomosis because of their stability, and faster handling. Further in vivo studies are required to evaluate functional outcomes and confirm safety.

Moldable Tissue-Sealant Hydrogels Composed of In Situ Cross-Linkable Polyethylene Glycol via Thiol-Michael Addition and Carbomers.

Moldable tissue-sealant hydrogels were developed herein by combining the yield stress fluidity of a Carbomer and in situ cross-linking of 3-arm PEG-thiol (PEG-SH) and 4-arm PEG-acrylate (PEG-AC). The Carbomer was mixed with each PEG oligomer to form two aqueous precursors: Carbomer/PEG-SH and Carbomer/PEG-AC. The two hydrogel precursors exhibited sufficient yield stress (>100 Pa) to prevent dripping from their placement on the tissue surface. Moreover, these hydrogel precursors exhibited rapid restructuring when the shear strain was repeatedly changed. These rheological properties contribute to the moldability of these hydrogel precursors. After mixing these two precursors, they were converted from yield-stress fluids to chemically cross-linked hydrogels, Carbomer/PEG hydrogel, via thiol-Michael addition. The gelation time was 5.0 and 11.2 min at 37 and 25 °C, respectively. In addition, the Carbomer/PEG hydrogels exhibited higher cellular viability than the pure Carbomer. They also showed stable adhesiveness and burst pressure resistance to various tissues, such as the skin, stomach, colon, and cecum of pigs. The hydrogels showed excellent tissue sealing in a cecum ligation and puncture model in mice and improved the survival rate due to their tissue adhesiveness and biocompatibility. The Carbomer/PEG hydrogel is a potential biocompatible tissue sealant that surgeons can mold. It was revealed that the combination of in situ cross-linkable PEG oligomers and yield stress fluid such as Carbomer is effective for developing the moldable tissue sealant without dripping of its hydrogel precursors.

A Pearl for Pretibial and Forearm Repair Following Mohs Micrographic Surgery.

Wound repair of the pretibial and forearm regions presents a challenge during dermatologic surgery as these areas are under significant tension and exhibit increased skin fragility. Various methodologies have been proposed for the closure and repair of such wounds, however, the use of the bilayered suture technique may be simpler and more effective than other techniques such as the pinch stitch, pully stitch, slip-knot stitch, pulley set-back dermal suture, horizontal mattress suture, pully stitch, and tandem pulley stitch. Our objective was to describe a novel method for the repair of pretibial and forearm wounds following Mohs micrographic surgery utilizing bilayered closure followed by tissue adhesive application.  J Drugs Dermatol. 2024;23(5):380.     doi:10.36849/JDD.7139  .

Novel Peripheral Intravenous Catheter Securement for Children and Catheter Failure Reduction: A Randomized Clinical Trial.

Importance: Peripheral intravenous catheters (PIVCs) facilitate essential treatment. Failure of these essential devices is frequent and new securement strategies may reduce failure and improve patient outcomes. Objective: To evaluate clinical effectiveness of novel PIVC securement technologies for children to reduce catheter failure. Design, Setting, and Participants: A 3-arm, parallel group, superiority randomized clinical trial was conducted at 2 regional Australian hospitals from February 5, 2020, to January 14, 2022. Children aged 6 months to 8 years who were anticipated to require admission with a PIVC for at least 24 hours of in hospital treatment were eligible. Data were analyzed from May 25, 2022, to February 20, 2024. Interventions: Participants were randomly allocated in a 1:1:1 ratio to standard care, bordered polyurethane (Tegaderm [3M]), integrated securement dressing (SorbaView SHIELD [Medline]), and integrated securement dressing with tissue adhesive (Secureport IV). One catheter was studied per patient. Main Outcomes and Measures: Primary outcome was PIVC failure, defined as premature cessation of PIVC function for any reason prior to completion of planned treatment. Secondary outcomes were PIVC complications (any time dislodgement, occlusion, infiltration, partial dislodgement, extravasation, device leaking, phlebitis, pain), PIVC longevity, intervention acceptability (clinicians, participants, caregivers; 0-10 scale), and pain on removal (participants and caregivers; 0-10 scale relevant to age), adverse events, and health care costs. Results: A total of 383 patients (51% female; median age 36 [25th-75th percentiles, 22-72] months) were randomized 134 to standard care, 118 to integrated securement dressing, and 131 to integrated securement dressing with tissue adhesive. PIVC failure was lowest in integrated securement dressing with tissue adhesive (15 [12%]; adjusted hazard ratio [aHR], 0.47; 95% CI, 0.26-0.84) compared with integrated securement dressing (24 [21%]; aHR, 0.78; 95% CI, 0.47-1.28) and standard care (43 [34%]). Direct costs were significantly lower for integrated securement dressing with tissue adhesive (median, Australian dollars [A$], 312 [A$1 is equal to $0.65 US dollars]; IQR, A$302-A$380) and integrated securement dressing (median, A$303; IQR, A$294-A$465) compared with standard care (median, A$341; IQR, A$297-A$592; P ≤ .002) when considering the economic burden related to failure of devices. PIVC longevity and intervention acceptability were similar across all groups. Conclusions and Relevance: In this study, PIVCs secured with integrated securement dressings and tissue adhesive, in comparison with standard care, bordered polyurethane dressings, were associated with significantly reduced PIVC failure, for children admitted to hospital via the emergency department. Further research should focus on implementation in inpatient units where prolonged dwell and reliable intravenous access is most needed. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12619001026112.

Protamine-grafted carboxymethyl chitosan based hydrogel with adhesive and long-term antibacterial properties for hemostasis and skin wound healing.

In this study, we developed a tissue-adhesive and long-term antibacterial hydrogel consisting of protamine (PRTM) grafted carboxymethyl chitosan (CMC) (PCMC), catechol groups modified CMC (DCMC), and oxidized hyaluronic acid (OHA), named DCMC-OHA-PCMC. According to the antibacterial experiments, the PCMC-treated groups showed obvious and long-lasting inhibition zones against E. coli (and S. aureus), and the corresponding diameters varied from 10.1 mm (and 15.3 mm) on day 1 to 9.8 mm (and 15.3 mm) on day 7. The DCMC-OHA-PCMC hydrogel treated groups also exhibited durable antibacterial ability against E. coli (and S. aureus), and the antibacterial rates changed from 99.3 ± 0.21 % (and 99.6 ± 0.36 %) on day 1 to 76.2 ± 1.74 % (and 84.2 ± 1.11 %) on day 5. Apart from good mechanical and tissue adhesion properties, the hydrogel had excellent hemostatic ability mainly because of the grafted positive-charged PRTM. As the animal assay results showed, the hydrogel was conducive to promoting the deposition of new collagen (0.84 ± 0.03), the regeneration of epidermis (98.91 ± 6.99 µm) and wound closure in the process of wound repairing. In conclusion, the presented outcomes underline the prospective potential of the multifunctional CMC-based hydrogel for applications in wound dressings.

Use of dynamic tissue system adhesive skin closure device and multi-tissue platform porcine xenograft to achieve primary closure after wide local excision of a melanoma.

BACKGROUND: Wide local excision with sentinel lymph node biopsy has been the standard of care for melanoma with a Breslow depth greater than 1 mm. Wide local excision with 1- to 2-cm margins can result in large wounds that cannot be primarily closed. Traditionally, management has included reconstruction with autologous flaps and skin grafting. CASE REPORT: The authors of this case report achieved successful closure of a large posterior calf wound after 2-cm-wide local excision of the melanoma biopsy site in a 61-year-old male. The dermal lesion was a Clark level IV superficial spreading malignant melanoma with Breslow depth of 1.1 mm. Wound closure was achieved with a DTS adhesive skin closure device coupled with MTP xenograft powder as a healing adjunct. CONCLUSION: The results of this patient's case indicate that DTS adhesive skin closure device should be considered as an additional option for the closure of large defects following wide local excision in the management of melanoma.

Multifunctional Self-Healing Carbon Dot-Gelatin Bioadhesive: Improved Tissue Adhesion with Simultaneous Drug Delivery, Optical Tracking, and Photoactivated Sterilization.

Bioadhesives with all-inclusive properties for simultaneous strong and robust adhesion, cohesion, tracking, drug delivery, self-sterilization, and nontoxicity are still farfetched. Herein, a carbon dot (CD) is made to infuse each of the above-desired aspects with gelatin, an inexpensive edible protein. The CD derived through controlled hydrothermal pyrolysis of dopamine and terephthaldehyde retained -NH2, -OH, -COOH, and, most importantly, -CHO functionality on the CD surface for efficient skin adhesion and cross-linking. Facile fabrication of CD-gelatin bioadhesive through covalent conjugation of -CHO of the CD with -NH2 of gelatin through Schiff base formation was accomplished. This imparts remarkable self-healing attributes as well as excellent adhesion and cohesion evident from physicomechanical analysis in a porcine skin model. Improved porosity of the bioadhesive allows loading hemin as a model drug whose disembarkment is tracked with intrinsic CD photoluminescence. In a significant achievement, antibiotic-free self-sterilization of bioadhesive is demonstrated through visible light (white LED, 23 W)-irradiated photosensitization of the CD to produce reactive oxygen species for annihilation of both Gram-positive and Gram-negative bacteria with exceptional efficacy (99.9%). Thus, a comprehensive CD-gelatin bioadhesive for superficial and localized wound management is reported as a promising step for the transformation of the bioadhesive domain through controlled nanotization for futuristic clinical translations.

Efficacy and safety of fibrin sealant application in patients undergoing thyroidectomy: a systematic review and meta-analysis.

Various studies have focused on the application of fibrin sealants (FS) in thyroid surgery. Utilizing a meta-analysis, this systematic review analyzed the findings of recent randomized controlled trials on the safety and efficacy of FS in patients who underwent thyroidectomy. The Cochrane Library, Web of Science, Embase, PubMed, and Medline databases were searched for relevant studies, without any language restrictions. Seven randomized controlled trials were included in the originally identified 69 studies. Overall, 652 patients received FS during thyroid surgery; their outcomes were compared with those of conventionally treated patients. The primary outcomes were total volume of wound drainage, length of hospitalization, and operative time. Significant differences were observed in the total volume of wound drainage (mean deviation (MD): -29.75, 95% confidence interval (CI): -55.39 to -4.11, P = 0.02), length of hospitalization (MD: -0.84, 95% CI: -1.02 to -0.66, P < 0.00001), and surgery duration (MD: -7.60, 95% CI: -14.75 to -0.45, P = 0.04). Secondary outcomes were seroma and hypoparathyroidism development. The risk of hypoparathyroidism did not differ between the FS and conventional groups (I = 0%, relative risk = 1.31, P = 0.38). Analysis of "seroma formation that required invasive treatment" indicated that FS showed some benefit (I2 = 8%, relative risk 0.44, P = 0.15). Heterogeneity among the different trials limited their conclusions. The meta-analysis showed that although FS use did not significantly reduce seroma or hypoparathyroidism incidence in patients after thyroidectomy, it significantly reduced the total drainage volume, length of hospitalization, and duration of surgery.

A Biodegradable Tissue Adhesive for Post-Extraction Alveolar Bone Regeneration under Ongoing Anticoagulation-A Microstructural Volumetric Analysis in a Rodent Model.

In addition to post-extraction bleeding, pronounced alveolar bone resorption is a very common complication after tooth extraction in patients undergoing anticoagulation therapy. The novel, biodegenerative, polyurethane adhesive VIVO has shown a positive effect on soft tissue regeneration and hemostasis. However, the regenerative potential of VIVO in terms of bone regeneration has not yet been explored. The present rodent study compared the post-extraction bone healing of a collagen sponge (COSP) and VIVO in the context of ongoing anticoagulation therapy. According to a split-mouth design, a total of 178 extraction sockets were generated under rivaroxaban treatment, of which 89 extraction sockets were treated with VIVO and 89 with COSP. Post-extraction bone analysis was conducted via in vivo micro-computed tomography (µCT), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX) after 5, 10, and 90 days. During the observation time of 90 days, µCT analysis revealed that VIVO and COSP led to significant increases in both bone volume and bone density (p ≤ 0.001). SEM images of the extraction sockets treated with either VIVO or COSP showed bone regeneration in the form of lamellar bone mass. Ratios of Ca/C and Ca/P observed via EDX indicated newly formed bone matrixes in both treatments after 90 days. There were no statistical differences between treatment with VIVO or COSP. The hemostatic agents VIVO and COSP were both able to prevent pronounced bone loss, and both demonstrated a strong positive influence on the bone regeneration of the alveolar ridge post-extraction.

Ultrafast gelling bioadhesive based on blood plasma and gelatin for wound closure and healing.

Tissue adhesives offer a plethora of advantages in achieving efficient wound closure over conventional sutures and staples. Such materials are of great value, especially in cases where suturing could potentially damage tissues or compromise blood flow or in cases of hard-to-reach areas. Besides providing wound closure, the tissue adhesives must also facilitate wound healing. Previously, plasma-based tissue adhesives and similar bioinspired strategies have been utilized to aid in wound healing. Still, their application is constrained by factors such as high cost, diminished biocompatibility, prolonged gelation times, inadequate swelling, quick resorption, as well as short-term and inconsistent efficacy. To address these limitations, we report the development of a highly biocompatible and ultrafast-gelling tissue adhesive hydrogels. Freeze-dried platelet-rich plasma, heat-denatured freeze-dried platelet-poor plasma, and gelatin were utilized as the base matrix. Gelation was initiated by adding tetrakis hydroxymethyl phosphonium chloride. The fabricated gels displayed rapid gelation (3-4 s), low swelling, increased proliferation, and migration against L929 cells and had porcine skin tissue adhesion strength similar to that of plasma-based commercial glue (Tisseel®).

Multifunctional polypeptide-based hydrogel bio-adhesives with pro-healing activities and their working principles.

Wound healing is a complex physiological process involving hemostasis, inflammation, proliferation, and tissue remodeling. Therefore, there is an urgent need for suitable wound dressings for effective and systematical wound management. Polypeptide-based hydrogel bio-adhesives offer unique advantages and are ideal candidates. However, comprehensive reviews on polypeptide-based hydrogel bio-adhesives for wound healing are still lacking. In this review, the physiological mechanisms and evaluation parameters of wound healing were first described in detail. Then, the working principles of hydrogel bio-adhesives were summarized. Recent advances made in multifunctional polypeptide-based hydrogel bio-adhesives involving gelatin, silk fibroin, fibrin, keratin, poly-γ-glutamic acid, ɛ-poly-lysine, serum albumin, and elastin with pro-healing activities in wound healing and tissue repair were reviewed. Finally, the current status, challenges, developments, and future trends of polypeptide-based hydrogel bio-adhesives were discussed, hoping that further developments would be stimulated to meet the growing needs of their clinical applications.

Photocurable extracellular matrix sealant for cessation of venous hemorrhage.

Hemorrhage is the second leading cause of death in patients under 46 years of age in the United States. Cessation of hemorrhage prevents hemorrhagic shock and tissue hypoxia. Controlling the bleed via direct pressure or tourniquet is often the first line of defense, but long-term care requires staples, hemostatic agents, or sealants that seal the vessel and restore blood flow. Here, we compare a new photocurable extracellular matrix sealant (pcECM) with low, medium, and high crosslink density formulations to a commercially available fibrin-based sealant, TISSEEL®. pcECM has potential uses in surgical and remote settings due to room temperature storage conditions and fast preparation time. Here, we determine if pcECM sealant can stop venous hemorrhage in a murine model, adhere to the wound site in vivo throughout the wound-healing process, and has the mechanical properties necessary for stopping hemorrhage. Adjusting pcECM crosslinking density significantly affected viscosity, swelling, burst strength, tensile strength, and elasticity of the sealant. 3-Dimensional ultrasound volume segmentations showed pcECM degrades to 17 ± 8% of its initial implant volume by day 28. Initially, local hemodynamic changes were observed, but returned close to baseline levels by day 28. Acute inflammation was observed near the puncture site in pcECM implanted mice, and we observed inflammatory markers at the 14-day explant for both sealants. pcECM and fibrin sealant successfully sealed the vessel in all cases, and consistently degraded over 14-28 days. pcECM is a durable sealant with tunable mechanical properties and possible uses in hemorrhage control and other surgical procedures.

Injectable Nanoengineered Adhesive Hydrogel for Treating Enterocutaneous Fistulas.

Enterocutaneous fistula (ECF) is a severe medical condition where an abnormal connection forms between the gastrointestinal tract and skin. ECFs are, in most cases, a result of surgical complications such as missed enterotomies or anastomotic leaks. The constant leakage of enteric and fecal contents from the fistula site leads to skin breakdown and increases the risk of infection. Despite advances in surgical techniques and postoperative management, ECF accounts for significant mortality rates, estimated between 15-20%, and causes debilitating morbidity. Therefore, there is a critical need for a simple and effective method to seal and heal ECF. Injectable hydrogels with combined properties of robust mechanical properties and cell infiltration/proliferation have the potential to block and heal ECF. Herein, we report the development of an injectable nanoengineered adhesive hydrogel (INAH) composed of a synthetic nanosilicate (Laponite®) and a gelatin-dopamine conjugate for treating ECF. The hydrogel undergoes fast cross-linking using a co-injection method, resulting in a matrix with improved mechanical and adhesive properties. INAH demonstrates appreciable blood clotting abilities and is cytocompatible with fibroblasts. The adhesive properties of the hydrogel are demonstrated in ex vivo adhesion models with skin and arteries, where the volume stability in the hydrated internal environment facilitates maintaining strong adhesion. In vivo assessments reveal that the INAH is biocompatible, supporting cell infiltration and extracellular matrix deposition while not forming fibrotic tissue. These findings suggest that this INAH holds promising translational potential for sealing and healing ECF.

Biochemical and biomechanical characterization of an autologous protein-based fibrin sealant for regenerative medicine.

Accidental events or surgical procedures usually lead to tissue injury. Fibrin sealants have proven to optimize the healing process but have some drawbacks due to their allogeneic nature. Autologous fibrin sealants present several advantages. The aim of this study is to evaluate the performance of a new autologous fibrin sealant based on Endoret®PRGF® technology (E-sealant). One of the most widely used commercial fibrin sealants (Tisseel®) was included as comparative Control. E-sealant´s hematological and biological properties were characterized. The coagulation kinetics and the microstructure were compared. Their rheological profile and biomechanical behavior were also recorded. Finally, the swelling/shrinkage capacity and the enzymatic degradation of adhesives were determined. E-sealant presented a moderate platelet concentration and physiological levels of fibrinogen and thrombin. It clotted 30 s after activation. The microstructure of E-sealant showed a homogeneous fibrillar scaffold with numerous and scattered platelet aggregates. In contrast, Control presented absence of blood cells and amorphous protein deposits. Although in different order of magnitude, both adhesives had similar rheological profiles and viscoelasticity. Control showed a higher hardness but both adhesives presented a pseudoplastic hydrogel nature with a shear thinning behavior. Regarding their adhesiveness, E-sealant presented a higher tensile strength before cohesive failure but their elastic stretching capacity and maximum elongation was similar. While E-sealant presented a significant shrinkage process, Control showed a slight swelling over time. In addition, E-sealant presented a high enzymatic resorption rate, while Control showed to withstand the biodegradation process in a significant way. E-sealant presents optimal biochemical and biomechanical properties suitable for its use as a fibrin sealant with regenerative purposes.