Table 2 Alternative biomaterials applied in other hemorrhage applications with potential for PTH
From: Topical biomaterials to prevent post-tonsillectomy hemorrhage
Biomaterial | Commercial Product | Mechanism of action | Application | Advantages | Drawbacks | Action/ resorption time | FDA approval (Y/N) | |
|---|---|---|---|---|---|---|---|---|
Scaffold/Matrix Agents | Absorbable gelatin medicated sponge [95, 96] (sponge or powder) | Gelfoam®, Surgifoam® | porous matrix for platelet adhesion and fibrin clot formation; increased volume can provide hemostasis [29] | little allergic activity [29] | Increased granuloma and infection [29] | 4–6 weeks | ||
microfibrillar collagen-based powder, sheets, or plugs | Colgel®, Helitene®, Avitene®, CollaPlug®, CollaTape® | bovine collagen provides a substrate that activates platelets and allows them to adhere, facilitate clot formation through the intrinsic coagulation pathway [29, 101] | Tonsil bleeding [102], epistaxis [103], cardiac surgery [104, 105] | does not swell [29] | Adhesions, foreign body reactions, or allergic reactions have been reported. Most often with Avitene [106]. | 8 weeks | ||
microfibrillar collagen-based atraumatic, bioresorbable, liquid hemostat spray | CoStasis® | combination of bovine collagen and bovine thrombin in a calcium chloride buffer and autologous obtained plasma that are mixed in equal volumes and administered intraoperatively. Fibrinogen from the patient’s plasma is cleaved by the thrombin in the collagen matrix | hepatic orthopedic cardiothoracic, and general surgical procedures [110, 111] | acceptable biocompatibility [112] | Low antigenicity of collagen and possible allergic reactions [113] | achieve hemostasis within 3 min in cardiac surgery [110], 10 min for general surgeries, hepatic and iliac crest surgery [111] | Y [114] | |
Microporous mucopolysaccharide spheres | Arista AH®, HemoStase MPH® | flowable potato starch powder engineered to dehydrate blood, enhance clotting, concentrate erythrocytes and platelets for more effective thrombus formation [29, 115] | cardiothoracic surgical procedures [116], cerebral hemostasis [117], nephrectomies [118], sinus [119], cardiac [110] | nonpyogenic, good safety record [29] | short resorption, limited efficacy compared to procoagulant hemostatic [29] | 24–48 h. | Y [120] | |
Biologic hemostats | Topical thrombin liquid (spray) | Bovine origin: Thrombin-JMI®, Thrombogen™ Human pooled: Evithrom®, Recombinant Human (rh): Recothrom® | Thrombin initiates cleavage of fibrinogen to fibrin, promoting clot formation [29] | comparative trial in liver resection, spine, peripheral arterial bypass, and dialysis access surgery [121] | RhThrombin reduced bleeding and thrombotic complications and less immunogenic than bovine thrombin [121] | Activation of autoimmune antibodies, causing profound coagulopathy [122], infectious disease concerns [29] | immediate | N bovine origin thrombin Y Evithrom [123] Y Recothrom [124] |
Platelet-rich fibrin membrane | Spin blood at 3000 rpm for 10 min to get fibrin clot: the middle layer between the red corpuscles at bottom and acellular plasma at the top. | Platelet cytokines, growth factors, and cells are entrapped and discharged in fibrin meshwork serving as a resorbable film [125], and platelets trigger blood clot and wound healing [125]. | hemostatic material for the treatment of oral lesions [126,127,128] | Cost-effective, simplified process, minimum blood manipulation and immunological reaction, promotes soft tissue healing | Need proper protocol and quick handling | – | N | |
Chitin/chitosan dressings | ChitoFlex®, HemCon®, Celox™ | Promote local vasoconstriction and serve as a scaffold for erythrocyte agglutination; physically occlude the wound site; stimulate fibroblast activation and collagen deposition [86] Interacts with red blood cells and platelets directly to for a clot independent of clotting factors [110] | Cardiac [110], common homeostatic dressing for US military and pre-hospital wound dressing. [110], dental [129] | Antimicrobial due to acidic PH [130], efficacy in acquiring hemostasis and promoted initial healing phases [29, 110],nonallergic, nonexothermic, low cost, able to function in a hypothermic environment [110] | requires dressing and substrate to be in contact with wound | immediate to complete wound healing | ||
Hemocoagulase liquid | Hemocoagulase agkistrodon | pharmacologic combination of coagulative proteins present in the venom of Bothrops jararaca or Bothrops atrox that works by directly cleaving fibrinogen to fibrin and activating factor X. Clot is thus formed independent of thrombin and will not break down in response to antithrombin [29, 134] | minor oral surgical procedures (impactions, simple extractions, transalveolar extractions) [135], postextraction bleeding [136] | Proven to significantly decrease postextraction bleeding [29] | Limitation in purchase and preparation | immediate | N | |
granular mineral zeolite-based hemostatic agent (powder in a gauze mesh) | QuikClot® | Zeolite absorbs water and concentrates coagulation factor, causes local dehydration with concentration of erythrocytes and platelets as well as activation of factor XII to initiate the coagulation cascade [29, 110, 137] | Cardiac surgeries [110], exsanguinating extremity wound and bleeding [131] | Cost-effective, stable | cannot be left in the wound site due to a foreign body reaction occurring | immediate | ||
alginate dressing | Silverlonâ„¢ Antimicrobial Calcium Alginate Dressing | Dehydration and concentration of erythrocytes and platelets, cationic initiation of coagulation cascade, barrier protection [139] | effective barrier to microbial penetration for moderate to heavy exuding wounds, and other surgical wounds [140] | Able to be removed with water without disrupting the underlying tissue healing | Not effective to handle a high flow of blood | immediate to complete wound healing | Y [141] | |
Tissue Adhesives | Cyanoacrylates liquid | Omnex® | The sealant polymerizes to form a flexible sealing film, which is adherent to both synthetic material and human tissue in a process that is independent of the patient’s clotting processes. | Safe, strong, non-toxic, flexible, biocompatible, prevented blood leakage along suture, diminished hemostasis in coagulopathy, reduced time to hemostasis and seal | if closed in a wound, can lead to tissue necrosis and local inflammation; also do not handle the tension on tissues especially well | immediate to wound healing. The seal degrades with time, breaking down into smaller absorbable fragments. | Y [144] | |
Polyethylene glycol hydrogel | CoSeal®, DuraSeal® | 2-phase application that results in the formation of a hydrogel matrix that becomes cross-linked with local proteins such as collagen [110] | Cardiac [145], lung [146], laparoscopic lymphadenectomy [147], urologic surgery | Found to be effective for urologic and vascular surgery and for CSF leak [29] | swells to 4 times its size | immediate | ||
Albumin-based–bovine-derived albumin cross-linked by glutaraldehyde | BioGlue® | Mixture of albumin-based-bovine-derived albumin with glyceraldehyde creates strong crosslinks generating a tough hemostatic and adhesive matrix [29]. | Cardiac [132], laparoscopic nephrectomy [150], secure hemostasis at cardiovascular anastomoses [151] | hemostatic and barrier protection | hypersensitivity reaction [29], impairs aortic growth [151], nerve tissue injury, cannot be used in pediatric cases as it impairs tissue growth [110]. | immediate/indeterminate 20–30 s and reaches bonding strength by 2 min [110] | Y [152] | |
Mucosal tissue dressing based on methyl cellulose [153] | US9381270B2Acclarent, Inc., Menlo Park, CA (US) | Certain embodiments provide a biodegradable film or cover ing that serves as a mechanical barrier to reduce pain caused | for reducing or eliminating pain after Surgical procedures related to mucosal tissue tonsillectomy, adenoidectomy, or other pharyngeal operations. | Reduce pain and bleeding, facilitate mucosal tissue healing | Not clinical tested yet | Expected to be dissolved at 14 days and stable for 5 days | N | |
Natural polymer based tissue adhesive (polysaccharides or partial hydrolysis derivatives or neutralization salts, chitosan and an alginate, carboxylic acid (acetic acid and lactic acid)) [154] | US20190038798A1 Ronnie Michael Hanes, Union Grove, AL (US); Adele Lamping Hanes, Union Grove, AL (US | intraoperatively applied on the tonsil fossa which is then closed with the adhesive or sutures, used postoperatively as external dressing by application as a gel, thin film device or dry powder, or any methods in combination. | Post – operative application for tonsillectomy or adenoidectomy surgery, internal tissue adhesive for surgery or wound repair, application to a burn or skin donor site. For internal use, an optional treatment to improve resistance of the activated adhesive to body fluids is also described . | Promote healing with enhanced adhesive properties | Not fully tested yet | – | N | |