Abstract
Wound healing, a critical biological process vital for tissue restoration, has spurred a global market exceeding $15 billion for wound care products and $12 billion for scar treatment. Chronic wounds lead to delayed or impaired wound healing. Natural bioactive compounds, prized for minimal side effects, stand out as promising candidates for effective wound healing. In response, researchers are turning to nanotechnology, employing the encapsulation of these agents into drug delivery carriers. Drug delivery system will play a crucial role in enabling targeted delivery of therapeutic agents to promote tissue regeneration and address underlying issues such as inflammation, infection, and impaired angiogenesis in chronic wound healing. Drug delivery carriers offer distinct advantages, exhibiting a substantial ratio of surface area to volume and altered physical and chemical properties. These carriers facilitate sustained and controlled release, proving particularly advantageous for the extended process of wound healing, that typically comprise a diverse range of components, integrating both natural and synthetic polymers. Additionally, they often incorporate bioactive molecules. Despite their properties, including poor solubility, rapid degradation, and limited bioavailability, various natural bioactive agents face challenges in clinical applications. With a global research, emphasis on harnessing nanomaterial for wound healing application, this research overview engages advancing drug delivery technologies to augment the effectiveness of tissue regeneration using bioactive molecules. Recent progress in drug delivery has poised to enhance the therapeutic efficacy of natural compounds in wound healing applications.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The datasets generated during the current study are available from the corresponding author on reasonable request.
References
Abd El-Baky RM, Ibrahim RA, Mohamed DS, Ahmed EF, Hashem ZS (2020) Prevalence of virulence genes and their association with antimicrobial resistance among pathogenic E. coli isolated from Egyptian patients with different clinical infections. Infectn Drug Res. https://doi.org/10.2147/IDR.S241073
Acar H, Ting JM, Srivastava S, LaBelle JL, Tirrell MV (2017) Molecular engineering solutions for therapeutic peptide delivery. Chem Soc Rev 46(21):6553–6569. https://doi.org/10.1039/C7CS00536A
Aitzetmüller MM, Machens HG, Duscher D (2021) Challenges and Opportunities in Drug Delivery for Wound Healing. Chronic Wounds Wound Dressings and Wound Healing, 37–49
Alaysuy O, Snari RM, Alfi AA, Aldawsari AM, Abu-Melha S, Khalifa ME, El-Metwaly NM (2022) Development of green and sustainable smart biochromic and therapeutic bandage using red cabbage (Brassica oleracea L. Var. capitata) extract encapsulated into alginate nanoparticles. Int J Biol Macromol 211:390–399
Algahtani MS, Ahmad MZ, Nourein IH, Albarqi HA, Alyami HS, Alyami MH, Ahmad J (2021) Preparation and characterization of curcumin nanoemulgel utilizing ultrasonication technique for wound healing: In vitro, ex vivo, and in vivo evaluation. Gels 7(4):213. https://doi.org/10.3390/gels7040213
Ali IH, Khalil IA, El-Sherbiny IM (2023) Design, development, in-vitro and in-vivo evaluation of polylactic acid-based multifunctional nanofibrous patches for efficient healing of diabetic wounds. Sci Rep 13(1):3215. https://doi.org/10.1038/s41598-023-29032-x
Altun M, Mericli Yapıcı B (2020) Detection of group a beta hemolytic streptococci species, emm, and exotoxin genes isolated from patients with tonsillopharyngitis. Curr Microbiol 77:2064–2070. https://doi.org/10.1007/s00284-020-01994-5
Alyoussef A, El-Gogary RI, Ahmed RF, Farid OAA, Bakeer RM, Nasr M (2021) The beneficial activity of curcumin and resveratrol loaded in nanoemulgel for healing of burn-induced wounds. J Drug Deliv Sci Technol. https://doi.org/10.1016/j.jddst.2021.102360
Amanat S, Taymouri S, Varshosaz J, Minaiyan M, Talebi A (2020) Carboxymethyl cellulose-based wafer enriched with resveratrol-loaded nanoparticles for enhanced wound healing. Drug Deliv Transl Res 10:1241–1254. https://doi.org/10.1007/s13346-020-00711-w
Amararathna M, Hoskin DW, Rupasinghe HPV (2022) Anthocyanin Encapsulated Nanoparticles as a Pulmonary Delivery System. Oxid Med Cell Longev. https://doi.org/10.1155/2022/1422929
Anwar M, Pervaiz F, Shoukat H, Noreen S, Shabbir K, Majeed A, Ijaz S (2021) Formulation and evaluation of interpenetrating network of xanthan gum and polyvinylpyrrolidone as a hydrophilic matrix for controlled drug delivery system. Polym Bull 78:59–80. https://doi.org/10.1007/s00289-019-03092-4
Arabaci C, Kenan AK (2020) "Beta hemolytic Streptococci strains isolated from clinical specimens, their characteristics and antibiotic susceptibility. J Surg Med 4(1):38–42
Armstrong DG, Galiano RD, Orgill DP, Glat PM, Carter MJ, Di Domenico LA, Zelen CM (2022) Multi-centre prospective randomised controlled clinical trial to evaluate a bioactive split thickness skin allograft vs standard of care in the treatment of diabetic foot ulcers. Int Wound J 19(4):932–944. https://doi.org/10.1111/iwj.13759
Askarizadeh A, Mashreghi M, Mirhadi E, Mirzavi F, Shargh VH, Badiee A, Jaafari MR (2023) Doxorubicin-loaded liposomes surface engineered with the matrix metalloproteinase-2 cleavable polyethylene glycol conjugate for cancer therapy. Cancer Nanotechnol 14(1):1–26. https://doi.org/10.1186/s12645-023-00169-8
Augustine R, Hasan A, Dalvi YB, Rehman SRU, Varghese R, Unni RN, Al Moustafa AE (2021) Growth factor loaded in situ photocrosslinkable poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/gelatin methacryloyl hybrid patch for diabetic wound healing. Mater Sci Eng C. https://doi.org/10.1016/j.msec.2020.111519
Badran MM, Alanazi AE, Ibrahim MA, Alshora DH, Taha EH, Alomrani A (2023) Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery. Polymers, In Vitro and In Vivo Studies. https://doi.org/10.3390/polym15193890
Bagheri M, Mostafavinia A, Abdollahifar MA, Amini A, Ghoreishi SK, Chien S, Bayat M (2020) Combined effects of metformin and photobiomodulation improve the proliferation phase of wound healing in type 2 diabetic rats. Biomed Pharmacother. https://doi.org/10.1016/j.biopha.2019.109776
Beken B, Serttas R, Yazicioglu M, Turkekul K, Erdogan S (2020) Quercetin Improves Inflammation, Oxidative Stress, and Impaired Wound Healing in Atopic Dermatitis Model of Human Keratinocytes. Pediatr Allergy Immunol Pulmonol 33(2):69–79. https://doi.org/10.1089/ped.2019.1137
Benoit DS, Overby CT, Sims KR, Ackun-Farmmer MA (2020) Drug delivery systems. Biomaterials Science; Elsevier. The Netherlands, Amsterdam, pp 1237–1266
Bhadran A, Shah T, Babanyinah GK, Polara H, Taslimy S, Biewer MC, Stefan MC (2023) Recent advances in polycaprolactones for anticancer drug delivery. Pharmaceutics 15(7):1977. https://doi.org/10.3390/pharmaceutics15071977
Bruun T, Rath E, Oppegaard O, Skrede S (2020) "Beta-hemolytic streptococci and necrotizing soft tissue infections. Necrot Soft Tissue Infect Clin Pathog Aspects. https://doi.org/10.1007/978-3-030-57616-5_6
Canedo-Dorantes L, Canedo-Ayala M (2019) Skin acute wound healing: a comprehensive review. Int J Inflamm. https://doi.org/10.1155/2019/3706315
Cardoso RV, Pereira PR, Freitas CS, Paschoalin VMF (2022) Trends in Drug Delivery Systems for Natural Bioactive Molecules to Treat Health Disorders: The Importance of Nano-Liposomes. Pharmaceutics. https://doi.org/10.3390/pharmaceutics14122808
Cetinkalp S, Gokce EH, Simsir I, Tuncay Tanrıverdi S, Dogan F, Biray Avcı C, Ozer O (2021) Comparative evaluation of clinical efficacy and safety of collagen laminin–based dermal matrix combined with resveratrol microparticles (Dermalix) and standard wound Care for Diabetic Foot Ulcers. Int J Low Extrem Wounds. https://doi.org/10.1177/1534734620907773
Chang MC, Kuo YJ, Hung KH, Peng CL, Chen KY, Yeh LK (2020) Liposomal dexamethasone–moxifloxacin nanoparticle combinations with collagen/gelatin/alginate hydrogel for corneal infection treatment and wound healing. Biomed Mater. https://doi.org/10.1088/1748-605X/ab9510
Chicharro-Alcantara D, Rubio-Zaragoza M, Damia-Gimenez E, Carrillo-Poveda JM, Cuervo-Serrato B, Pelaez-Gorrea P, Sopena-Juncosa JJ (2018) Platelet rich plasma: new insights for cutaneous wound healing management. J Funct Biomater 9(1):10. https://doi.org/10.3390/jfb9010010
Chittasupho C, Manthaisong A, Okonogi S, Tadtong S, Samee W (2021) Effects of Quercetin and Curcumin Combination on Antibacterial, Antioxidant, In Vitro Wound Healing and Migration of Human Dermal Fibroblast Cells. Int J Mol Sci 23(1):142. https://doi.org/10.3390/ijms23010142
Chong DL, Trinder S, Labelle M, Rodriguez-Justo M, Hughes S, Holmes AM, Porter JC (2020) Platelet-derived transforming growth factor-β1 promotes keratinocyte proliferation in cutaneous wound healing. J Tissue Eng Regen Med 14(4):645–649. https://doi.org/10.1002/term.3022
Conte R, De Luca I, Valentino A, Cerruti P, Pedram P, Cabrera-Barjas G, Moeini A, Calarco A (2023) Hyaluronic Acid Hydrogel Containing Resveratrol-Loaded Chitosan Nanoparticles as an Adjuvant in Atopic Dermatitis Treatment. J Funct Biomater 14(2):82. https://doi.org/10.3390/jfb14020082
Copes F, Pien N, Van Vlierberghe S, Boccafoschi F, Mantovani D (2019) Collagen-based tissue engineering strategies for vascular medicine. mFront Bioeng Biotechnol. https://doi.org/10.3389/fbioe.2019.00166
Croitoru AM, Karaçelebi Y, Saatcioglu E, Altan E, Ulag S, Aydogan HK, Ficai A (2021) Electrically triggered drug delivery from novel electrospun poly (lactic acid)/graphene oxide/quercetin fibrous scaffolds for wound dressing applications. Pharmaceutics 13(7):957. https://doi.org/10.3390/pharmaceutics13070957
Cui L, Liang J, Liu H, Zhang K, Li J (2020) Nanomaterials for angiogenesis in skin tissue engineering. Tissue Eng B Rev 26(3):203–216
Damrongrungruang T, Paphangkorakit J, Limsitthichaikoon S, Khampaenjiraroch B, Davies MJ, Sungthong B, Priprem A (2021) Anthocyanin complex niosome gel accelerates oral wound healing: In vitro and clinical studies. Nanomed Nanotechnol Biol Med. https://doi.org/10.1016/j.nano.2021.102423
Del Amo C, Perez-Valle A, Perez-Zabala E, Perez-del-Pecho K, Larrazabal A et al (2020) Wound dressing selection is critical to enhance platelet-rich fibrin activities in wound care. Int J Mol Sci 21(2):624. https://doi.org/10.3390/ijms21020624
Delavary BM, van der Veer WM, van Egmond M, Niessen FB, Beelen RH (2011) Macrophages in skin injury and repair. Immunobio 216(7):753–762. https://doi.org/10.1016/j.imbio.2011.01.001
Desai N, Rana D, Salave S, Gupta R, Patel P et al (2023) Chitosan: A Potential Biopolymer in Drug Delivery and Biomedical Applications. Pharmaceutics 15(4):1313. https://doi.org/10.3390/pharmaceutics15041313
Devi KD, Khandait M, Sharma M, Sardar M, Singh A, Saha R, Devi LS (2023) Prevalence of multidrug-resistant Gram-negative bacteria causing pyogenic infections at a tertiary care hospital in Haryana. MGM J Med Sci. https://doi.org/10.4103/mgmj.mgmj_66_23
Di Cristo F, Valentino A, De Luca I, Peluso G, Bonadies I, Di Salle A, Calarco A (2023) Polylactic Acid/Poly (vinylpyrrolidone) Co-Electrospun Fibrous Membrane as a Tunable Quercetin Delivery Platform for Diabetic Wounds. Pharmaceutics 15(3):805. https://doi.org/10.3390/pharmaceutics15030805
Domínguez-Robles J, Cuartas-Gomez E, Dynes S, Utomo E et al (2023) Poly (caprolactone)/lignin-based 3D-printed dressings loaded with a novel combination of bioactive agents for wound-healing applications. Sustainable Mater Technol. https://doi.org/10.1016/j.susmat.2023.e00581
Dwivedi C, Pandey I, Pandey H, Patil S, Mishra SB et al (2018) In vivo diabetic wound healing with nanofibrous scaffolds modified with gentamicin and recombinant human epidermal growth factor. J Biomed Mater Res A 106(3):641–651. https://doi.org/10.1002/jbm.a.36268
Dwivedi C, Pandey I, Pandey H, Ramteke PW, Pandey AC, Mishra SB, Patil S (2017) Electrospun nanofibrous scaffold as a potential carrier of antimicrobial therapeutics for diabetic wound healing and tissue regeneration. In Nano-and Microscale Drug Delivery Systems (pp. 147–164)
Ellis S, Lin EJ, Tartar D (2018) Immunology of wound healing. Curr Derm Rep 7:350–358. https://doi.org/10.1007/s13671-018-0234-9
El Fawal G, Hong H, Mo X, Wang H (2021) Fabrication of scaffold based on gelatin and polycaprolactone (PCL) for wound dressing application. J Drug Deliv Sci Technol 63:102501. https://doi.org/10.1016/j.jddst.2021.102501
Eming SA (2019) Introduction to Wound Healing and Tissue Repair. In: Matucci-Cerinic M, Denton C (eds) Atlas of Ulcers in Systemic Sclerosis Springer Cham https://doi.org/10.1007/978-3-319-98477-3_5
Erci F, Sariipek FB (2023) Fabrication of antimicrobial poly (3-hydroxybuthyrate)/poly (ε-caprolactone) nanofibrous mats loaded with curcumin/β-cylodextrin inclusion complex as potential wound dressing. J Drug Deliv Sci Technol. https://doi.org/10.1016/j.jddst.2023.105023
Fadeeva IV, Deyneko DV, Knotko AV, Olkhov AA, Slukin PV, Davydova GA, Rau JV (2023) Antibacterial Composite Material Based on Polyhydroxybutyrate and Zn-Doped Brushite Cement. Polymers 15(9):2106. https://doi.org/10.3390/polym15092106
Farhat F, Sohail SS, Siddiqui F, Irshad RR, Madsen DO (2023) Curcumin in Wound Healing—A Bibliometric Analysis. Life 13(1):143. https://doi.org/10.3390/life13010143
Farokhi M, Mottaghitalab F, Reis RL, Ramakrishna S, Kundu SC (2020) Functionalized silk fibroin nanofibers as drug carriers: Advantages and challenges. J Control Release 321:324–347. https://doi.org/10.1016/j.jconrel.2020.02.022
Farzaei MH, Derayat P, Pourmanouchehri Z, Kahrarian M, Samimi Z, Hajialyani M, Behbood L (2023) Characterization and evaluation of antibacterial and wound healing activity of naringenin-loaded polyethylene glycol/polycaprolactone electrospun nanofibers. J Drug Deliv Sci Technol. https://doi.org/10.1016/j.jddst.2023.104182
Fatima T, Jolly R, Mushahid F, Khan N, Umar MS, Owais M, Shakir M (2023) Combinatorial approach to fabricate silica doped polyvinyl alcohol/ hydroxyapatite/ carrageenan nanocomposite for bone regeneration applications. Polym Adv Technol. https://doi.org/10.1002/pat.6048
Felgines C, Texier O, Besson C, Lyan B, Lamaison JL, Scalbert A (2007) Strawberry pelargonidin glycosides are excreted in urine as intact glycosides and glucuronidated pelargonidin derivatives in rats. Br J Nutr 98(6):1126–1131
Feroz S, Muhammad N, Ratnayake J, Dias G (2020) Keratin-Based materials for biomedical applications. Bioact Mater 5(3):496–509. https://doi.org/10.1016/j.bioactmat.2020.04.007
Ferroni C, Varchi G (2021) Keratin-based nanoparticles as drug delivery carriers. Appl Sci 11(20):9417. https://doi.org/10.3390/app11209417
Feyzioglu-Demir E, Uzum OB, Akgol S (2023) Swelling and diffusion behaviour of spherical morphological polymeric hydrogel membranes (SMPHMs) containing epoxy groups and their application as drug release systems. Polym Bull 80(6):6567–6590. https://doi.org/10.1007/s00289-022-04368-y
Fields AC, Pradarelli JC, Itani KM (2020) Preventing surgical site infections: looking beyond the current guidelines. JAMA 323(11):1087–1088. https://doi.org/10.1001/jama.2019.20830
Flowers L, Grice EA (2020) The skin microbiota: balancing risk and reward. Cell Host Microbe 28(2):190–200. https://doi.org/10.1016/j.chom.2020.06.017
Fu CP, Cai XY, Chen SL, Yu HW, Fang Y, Feng XC, Li CY (2023) Hyaluronic Acid-Based Nanocarriers for Anticancer Drug Delivery. Polymers 15(10):2317. https://doi.org/10.3390/polym15102317
Gao J, Karp JM, Langer R, Joshi N (2023) The future of drug delivery. Chem Mater 35(2):359–363. https://doi.org/10.1021/acs.chemmater.2c03003
Garcia LV, Silva D, Costa MM, Armes H, Salema-Oom M, Saramago B, Serro AP (2023) Antiseptic-Loaded Casein Hydrogels for Wound Dressings. Pharmaceutics 15(2):334. https://doi.org/10.3390/pharmaceutics15020334
Gauglitz GG, Shahrokhi S, Williams FN (2017) Burn wound infection and sepsis. UpToDate. https://www.uptodate.com/contents/burn-wound-infection-and-sepsis.
Gaur S, Singhal S, Gaur S, Mishra R, Pandey I, Bajpai S (2022) Mesalazine based topical hydrogel formulation enhances anti-oxidant and cytokine activity in wounded STZ-induced mice. J Drug Deliv Ther 12(2):51–57
Gemeda N, Tadele A, Lemma H, Girma B, Addis G, Tesfaye B, Debella A (2018) Development characterization and evaluation of novel broad-spectrum antimicrobial topical formulations from Cymbopogon martini (Roxb.) W Watson essential oil. Evid Based Complement Alternat Med. https://doi.org/10.1155/2018/9812093
Ghasemi S, Alibabaie A, Saberi R, Esmaeili M, Semnani D, Karbasi S (2023) Evaluation of the effects of zein incorporation on physical, mechanical, and biological properties of polyhydroxybutyrate electrospun scaffold for bone tissue engineering applications. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2023.126843
Goormaghtigh F, Van Bambeke F (2024) Understanding staphylococcus aureus internalization and induction of antimicrobial tolerance. Expert Rev Anti-Infect Ther. https://doi.org/10.1080/14787210.2024.2303018
Gorska A, Krupa A, Majda D, Kulinowski P, Kurek M, Weglarz WP, Jachowicz R (2021) Poly (vinyl alcohol) cryogel membranes loaded with resveratrol as potential active wound dressings. AAPS PharmSciTech 22:1–14. https://doi.org/10.1208/s12249-021-01976-1
Guo Y, Huang J, Fang Y, Huang H, Wu J (2022) 1D, 2D, and 3D scaffolds promoting angiogenesis for enhanced wound healing. Chem Eng J. https://doi.org/10.1016/j.cej.2022.134690
Gupta BP, Thakur N, Jain NP, Banweer J, Jain S (2010) Osmotically controlled drug delivery system with associated drugs. J Pharm Pharm Sci 13(4):571–588
Gushiken LFS, Beserra FP, Bastos JK, Jackson CJ, Pellizzon CH (2021) Cutaneous Wound Healing: An Update from Physiopathology to Current Therapies. Life (basel, Switzerland) 11(7):665. https://doi.org/10.3390/life11070665
Hamza KH, El-Shanshory AA, Agwa MM, Abo-Alkasem MI, El-Fakharany EM, Abdelsattar AS, Soliman HM (2023) Topically Applied Biopolymer-Based Tri-Layered Hierarchically Structured Nanofibrous Scaffold with a Self-Pumping Effect for Accelerated Full-Thickness Wound Healing in a Rat Model. Pharmaceutic 15(5):1518. https://doi.org/10.3390/pharmaceutics15051518
Hao J, Lv A, Li X, Li Y (2023) A Convergent fabrication of silk fibroin nanoparticles on quercetin loaded metal-organic frameworks for promising nanocarrier of myocardial infraction. Heliyon. https://doi.org/10.1016/j.heliyon.2023.e20746
Haque S, Kotcherlakota R, Bhamidipati P, Muralidharan K, Sreedhar B, Amanchy R, Patra CR (2023) Smartly Engineered Casein Manganese Oxide Nanobiomaterials and Its Potential Therapeutic Angiogenesis Applications for Wound Healing and Limb Ischemia. Adv Ther 6(9):2300142. https://doi.org/10.1002/adtp.202300142
Hardenia A, Maheshwari N, Hardenia SS, Dwivedi SK, Maheshwari R, Tekade RK. (2019) Scientific rationale for designing controlled drug delivery systems. In Basic Fundamentals of Drug Delivery (pp. 1–28) Academic Press. https://doi.org/10.1016/B978-0-12-817909-3.00001
Hariyadi DM, Islam N (2020) Current Status of Alginate in Drug Delivery. Adv Pharmacol Pharm Sci. https://doi.org/10.1155/2020/8886095
He Y, Zhao W, Dong Z, Ji Y et al (2021) A biodegradable antibacterial alginate/carboxymethyl chitosan/Kangfuxin sponges for promoting blood coagulation and full-thickness wound healing. Int J Biol Macromol 167:182–192. https://doi.org/10.1016/j.ijbiomac.2020.11.168
He H, Zhang X, Du L, Ye M, Lu Y, Xue J, Wu J, Shuai X (2022) Molecular imaging nanoprobes for theranostic applications. Adv Drug Deliv Rev. https://doi.org/10.1016/j.addr.2022.114320
He S, Bai J, Liu Y, Zeng Y et al (2023) A polyglutamic acid/tannic acid-based nano drug delivery system: Antibacterial, immunoregulation and sustained therapeutic strategies for oral ulcers. Int J Pharm. https://doi.org/10.1016/j.ijpharm.2023.123607
Honnegowda TM, Kumar P, Udupa EGP, Kumar S, Kumar U, Rao P (2015) Role of angiogenesis and angiogenic factors in acute and chronic wound healing. Plast Aesthet Res 2:243–249. https://doi.org/10.4103/2347-9264.165438
Horn DL, Roberts EA, Shen J, Chan JD, Bulger EM, Weiss NS, Lynch JB, Bryson-Cahn C, Robinson BRH (2021) Outcomes of β-Hemolytic Streptococcal Necrotizing Skin and Soft-tissue Infections and the Impact of Clindamycin Resistance. Clin Infect Dis 73(11):e4592–e4598. https://doi.org/10.1093/cid/ciaa976
Hosie I & KANNAN B (2021). Multilayer nanofibres with bioactive compositions for wound healing management, WO2021015631A1, PCT/NZ 2020/050077.https://doi.org/10.1016/B978-0-12-817909-3.00011-X
Hu Y, Xiong Y, Zhu Y, Zhou F, Liu X, Chen S, Chen L (2023) Copper-Epigallocatechin Gallate Enhances Therapeutic Effects of 3D-Printed Dermal Scaffolds in Mitigating Diabetic Wound Scarring. ACS Appl Mater Interfaces 15(32):38230–38246. https://doi.org/10.1021/acsami.3c04733
Huang YZ, Gou M, Da LC, Zhang WQ, Xie HQ (2020) Mesenchymal stem cells for chronic wound healing: current status of preclinical and clinical studies. Tissue Eng Part B Rev 26(6):555–570. https://doi.org/10.1089/ten.teb.2019.0351
Huang HC, Chen Y, Hu J, Guo XT, Zhou SR, Yang QQ, Peng YH (2023a) Quercetin and its derivatives for wound healing in rats/mice: Evidence from animal studies and insight into molecular mechanisms. Int Wound J. https://doi.org/10.1111/iwj.14389
Huang HJ, Huang SY, Wang TH, Lin TY et al (2023b) Clay nanosheets simultaneously intercalated and stabilized by PEGylated chitosan as drug delivery vehicles for cancer chemotherapy. Carbohydr Polym. https://doi.org/10.1016/j.carbpol.2022.120390
Hubatsch I, Ragnarsson EG, Artursson P (2007) Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nat Protoc 2(9):2111–2119. https://doi.org/10.1038/nprot.2007.303
IDCRP (2020).Wound infections. https://www.idcrp.org/wound-infections
Ijinu TP, De Lellis LF, Shanmugarama S, Perez-Gregorio R, Sasikumar P, Ullah H, Daglia M (2023) Anthocyanins as Immunomodulatory Dietary Supplements: A Nutraceutical Perspective and Micro-/Nano-Strategies for Enhanced Bioavailability. Nutrients 15(19):4152. https://doi.org/10.3390/nu15194152
Isopencu GO, Covaliu-Mierla CI, Deleanu IM (2023) From Plants to Wound Dressing and Transdermal Delivery of Bioactive Compounds. Plants. https://doi.org/10.3390/plants12142661
Jain KK (2020) An overview of drug delivery systems. Drug Deliv Syst. https://doi.org/10.1007/978-1-4939-9798-5_1
Jangde R, Srivastava S, Singh MR, Singh D (2018) In vitro and In vivo characterization of quercetin loaded multiphase hydrogel for wound healing application. Int J Biol Macromol 115:1211–1217. https://doi.org/10.1016/j.ijbiomac.2018.05.010
Jelodari S, Daemi H, Mohammadi P, Verdi JJ, Al-Awady M, Ai J, Azami M (2023) Assessment of the Efficacy of an LL-37-Encapsulated Keratin Hydrogel for the Treatment of Full-Thickness Wounds. ACS Appl Bio Mater. https://doi.org/10.1021/acsabm.2c01068
Ji X, Meng Y, Wang Q et al (2023) Cysteine-Based Redox-Responsive Nanoparticles for Fibroblast-Targeted Drug Delivery in the Treatment of Myocardial Infarction. ACS Nano 17(6):5421–5434. https://doi.org/10.1021/acsnano.2c10042
Jia Y, Shao JH, Zhang KW, Zou ML, Teng YY, Tian F, Yuan FL (2022) Emerging effects of resveratrol on wound healing: A Comprehensive Review. Mol. https://doi.org/10.3390/molecules27196736
Jimi S, Saparov A, Takagi S (2021) Cellular and molecular mechanisms at the proliferation stage in wound healing: From scarring to tissue regeneration. Front Cell Dev Biol. https://doi.org/10.3389/fcell.2021.659089
Jin SG, Yousaf AM, Jang SW, Son MW, Kim KS et al (2015) In vivo wound-healing effects of novel benzalkonium chloride-loaded hydrocolloid wound dressing. Drug Dev Res 76(3):157–165. https://doi.org/10.1002/ddr.21253
Joseph TM, Kallingal A, Suresh AM, Mahapatra DK, Hasanin MS, Haponiuk J, Thomas S (2023) 3D printing of polylactic acid: recent advances and opportunities. Int J Adv Manuf Technol 125(3–4):1015–1035. https://doi.org/10.1007/s00170-022-10795-y
Kalalinia F, Taherzadeh Z, Jirofti N, Amiri N et al (2021) Evaluation of wound healing efficiency of vancomycin-loaded electrospun chitosan/poly ethylene oxide nanofibers in full thickness wound model of rat. Int J Biol Macromol 177:100–110. https://doi.org/10.1016/j.ijbiomac.2021.01.209
Kamaly N, Yameen B, Wu J, Farokhzad OC (2016) Degradable controlled-release polymers and polymeric nanoparticles: mechanisms of controlling drug release. Chem Rev 116(4):2602–2663. https://doi.org/10.1021/acs.chemrev.5b00346
Kar AK, Singh A, Dhiman N, Purohit MP, Jagdale P, Kamthan M, Patnaik S (2019) Polymer-assisted in situ synthesis of silver nanoparticles with epigallocatechin gallate (EGCG) impregnated wound patch potentiate controlled inflammatory responses for brisk wound healing. Int J Nanomed. https://doi.org/10.2147/IJN.S228462
Kar AK, Singh A, Singh D, Shraogi N, Verma R, Saji J, Patnaik S (2022) Biopolymeric composite hydrogel loaded with silver NPs and epigallocatechin gallate (EGCG) effectively manages ROS for rapid wound healing in type II diabetic wounds. Int J Biol Macromol 218:506–518. https://doi.org/10.1016/j.ijbiomac.2022.06.196
Karppinen SM, Heljasvaara R, Gullberg D, Tasanen K, Pihlajaniemi T (2019) Toward understanding scarless skin wound healing and pathological scarring. F1000Research F1000 Faculty Rev-787 https://doi.org/10.12688/f1000research.18293.1
Kenawy ERS, Kamoun EA, Ghaly ZS, Shokr ABM, El-Meligy MA, Mahmoud YAG (2023) Novel physically cross-linked curcumin-loaded PVA/aloe vera hydrogel membranes for acceleration of topical wound healing: In vitro and in vivo experiments. Arab J Sci Eng 48(1):497–514. https://doi.org/10.1007/s13369-022-07283-6
Khatun S, Pebam M, Putta CL, Rengan AK (2023) Camptothecin loaded casein nanosystem for tuning the therapeutic efficacy against highly metastatic triple-negative breast cancer cells. Biomater Sci 11(7):2518–2530. https://doi.org/10.1039/D2BM01814D
Khushbu JR (2023) Thermal stability and optimization of graphene oxide incorporated chitosan and sodium alginate based nanocomposite containing inclusion complexes of paracetamol and β-cyclodextrin for prolonged drug delivery systems. Polym Bull 80(2):1751–1772. https://doi.org/10.1007/s00289-022-04157-7
Kim YE, Jung HY, Park N, Kim J (2023) Adhesive Composite Hydrogel Patch for Sustained Transdermal Drug Delivery To Treat Atopic Dermatitis. Chem Mater 35(3):1209–1217. https://doi.org/10.1021/acs.chemmater.2c03234
Kirsner RS, Margolis DJ, Baldursson BT, Petursdottir K, Davidsson OB, Weir D, Lantis JC (2020) Fish skin grafts compared to human amnion/chorion membrane allografts: a double-blind, prospective, randomized clinical trial of acute wound healing. Wound Repair and Regeneration 28(1):75–80. https://doi.org/10.1111/wrr.12761
Kolosova OY, Shaikhaliev AI, Krasnov MS, Bondar IM, Sidorskii EV, Sorokina EV, Lozinsky VI (2023) Cryostructuring of Polymeric Systems: 64. Preparation and Properties of Poly (vinyl alcohol)-Based Cryogels Loaded with Antimicrobial Drugs and Assessment of the Potential of Such Gel Materials to Perform as Gel Implants for the Treatment of Infected Wounds. Gels 9(2):113
Komi DEA, Khomtchouk K, Santa Maria PL (2020) A review of the contribution of mast cells in wound healing: involved molecular and cellular mechanisms. Clin Rev Allergy Immunol 58:298–312. https://doi.org/10.1007/s12016-019-08729-w
Kopecek J (2013) Polymer–drug conjugates: Origins, progress to date and future directions. Adv Drug Deliv Rev 65(1):49–59. https://doi.org/10.1016/j.addr.2012.10.014
Ku MS (2008) Use of the biopharmaceutical classification system in early drug development. AAPS J 10:208–212. https://doi.org/10.1208/s12248-008-9020-0
Kumari A, Raina N, Wahi A, Goh KW, Sharma P, Nagpal R, Jain A, Ming LC, Gupta M (2022) Wound-Healing Effects of Curcumin and Its Nanoformulations: A ComprehensiveReview. Pharmaceutics 14(11):2288. https://doi.org/10.3390/pharmaceutics14112288
Kurangi B, Jalalpure S, Jagwani S (2021) Formulation and evaluation of resveratrol loaded cubosomal nanoformulation for topical delivery. Curr Drug Deliv 18(5):607–619. https://doi.org/10.2174/1567201817666200902150646
Lang J, Yang C, Liu L, Li L, Wu L, Liu Y, Yang C (2021) High glucose activates ERK1/2 to stabilize AP1 and increase MMP9 expression in diabetic foot ulcers. Exp Cell Res. https://doi.org/10.1016/j.yexcr.2021.112550
Lara-Rico R, López-Badillo CM, Claudio-Rizo JA, Cabrera-Munguía DA, Becerra-Rodríguez JJ, Espinosa-Neira R, Cruz-Ortiz BR (2023) Smart hydrogels based on semi-interpenetrating polymeric networks of collagen-polyurethane-alginate for soft/hard tissue healing, drug delivery devices, and anticancer therapies. Biopolymers. https://doi.org/10.1002/bip.23538
Leng Q, Li Y, Pang X, Wang B, Wu Z et al (2020a) Curcumin nanoparticles incorporated in PVA/collagen composite films promote wound healing. Drug Deliv 27(1):1676–1685. https://doi.org/10.1080/10717544.2020.1853280
Leng Q, Li Y, Pang X, Wang B, Wu Z, Lu Y, Fu S (2020b) Curcumin nanoparticles incorporated in PVA/collagen composite films promote wound healing. Drug Delivery 27(1):1676–1685. https://doi.org/10.1080/10717544.2020.1853280
Li B, Wang J, Gui Q, Yang H (2020) Drug-loaded chitosan film prepared via facile solution casting and air-drying of plain water-based chitosan solution for ocular drug delivery. Bioact Mater 5(3):577–583. https://doi.org/10.1016/j.bioactmat.2020.04.013
Li Y, Liu Y, Li R, Bai H, Zhu Z, Zhu L, Huang L (2021) Collagen-based biomaterials for bone tissue engineering. Mater Des. https://doi.org/10.1016/j.matdes.2021.110049
Liang Y, Zhao X, Hu T, Chen B, Yin Z, Ma PX, Guo B (2019) Adhesive hemostatic conducting injectable composite hydrogels with sustained drug release and photothermal antibacterial activity to promote full-thickness skin regeneration during wound healing. Small 15(12):1900046. https://doi.org/10.1002/smll.201900046
Linz MS, Mattappallil A, Finkel D, Parker D (2023) Clinical Impact of Staphylococcus aureus Skin and Soft Tissue Infections. Antibiotics 12(3):557. https://doi.org/10.3390/antibiotics12030557
Liu D, Yang F, Xiong F, Gu N (2016) The smart drug delivery system and its clinical potential. Theranostics 6(9):1306. https://doi.org/10.7150/thno.14858
Liu G, Zhou Y, Xu Z, Bao Z, Zheng L, Wu J (2023) Janus hydrogel with dual antibacterial and angiogenesis functions for enhanced diabetic wound healing. Chin Chem Lett. https://doi.org/10.1016/j.cclet.2022.07.048
Lv Q, Deng J, Chen Y, Wang Y, Liu B, Liu J (2020) Engineered human adipose stem-cell-derived exosomes loaded with miR-21–5p to promote diabetic cutaneous wound healing. Mol Pharmaceutics 17(5):1723–1733. https://doi.org/10.1021/acs.molpharmaceut.0c00177
Ma W, Zhou M, Dong W, Zhao S, Wang Y, Yao J, Zhang M (2021) A bi-layered scaffold of a poly (lactic-co-glycolic acid) nanofiber mat and an alginate–gelatin hydrogel for wound healing. J Mater Chem B 9(36):7492–7505. https://doi.org/10.1039/d1tb01039e
Maouia A, Rebetz J, Kapur R, Semple JW (2020) The immune nature of platelets revisited. Transfus Med Rev 34(4):209–220. https://doi.org/10.1016/j.tmrv.2020.09.005
Markets and Markets (2021) Pharmaceutical drug delivery market by route of administration (oral, injectors, implantable, syrups, gels, pulmonary, solutions, tablets, syringes), application (cancer, diabetes), facility of use (hospitals), COVID-19 Impact - Forecast to 2026
Marusina AI, Merleev AA, Luna JI, Olney L, Haigh NE, Yoon D, Maverakis E (2020) Tunable hydrogels for mesenchymal stem cell delivery: Integrin-induced transcriptome alterations and hydrogel optimization for human wound healing. Stem Cells 38(2):231–245. https://doi.org/10.1002/stem.3105
Masoumi B, Mokhtary M, Rastkar MB, Mohtat B, Marandi GB, Djahaniani H (2023) Preparation and Characterization of Magnetic Gelatin-Polyvinyl Alcohol Hydrogel for using in the Release of Furosemide Drug. J Appl Chem Res 17(1):8–20
Mi Y, Zhong L, Lu S, Hu P, Pan Y, Ma X, Yan B, Wei Z, Yang G (2022) Quercetin promotes cutaneous wound healing in mice through Wnt/β-catenin signaling pathway. J Ethnopharmacol. https://doi.org/10.1016/j.jep.2022.115066
Mircioiu C, Voicu V, Anuta V, Tudose A, Celia C, Paolino D et al (2019) Mathematical modeling of release kinetics from supramolecular drug delivery systems. Pharmaceutics 11(3):140. https://doi.org/10.3390/pharmaceutics11030140
Mirhaj M, Varshosaz J, Labbaf S, Emadi R, Seifalian AM, Sharifianjazi F, Tavakoli M (2023) Mupirocin loaded core-shell pluronic-pectin-keratin nanofibers improve human keratinocytes behavior, angiogenic activity and wound healing. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2023.126700
Mohanta M, Thirugnanam A (2023) Development of multifunctional commercial pure titanium-polyethylene glycol drug-eluting substrates with enhanced optical and antithrombotic properties. Cardiovasc Eng Technol 14(1):37–51. https://doi.org/10.1007/s13239-022-00637-z
Mohanty C, Sahoo SK (2017) Curcumin and its topical formulations for wound healing applications. Drug Discov Today 22(10):1582–1592. https://doi.org/10.1016/j.drudis.2017.07.001
Monika P, Chandraprabha MN, Rangarajan A, Waiker PV, Chidambara Murthy KN (2022) Challenges in Healing Wound: Role of Complementary and Alternative Medicine. Front Nutr. https://doi.org/10.3389/fnut.2021.791899
Monnheimer M, Cooper P, Amegbletor HK, Pellio T, Groß U, Pfeifer Y, Schulze MH (2021) High Prevalence of Carbapenemase-Producing Acinetobacter baumannii in Wound Infections, Ghana, 2017/2018. Microorganisms 9(3):537. https://doi.org/10.3390/microorganisms9030537
Munier AL, Biard L, Legrand M, Rousseau C, Lafaurie M, Donay JL, Molina JM (2019) Incidence, risk factors and outcome of multi-drug resistant Acinetobacter baumannii nosocomial infections during an outbreak in a burn unit. Int J Infect Dis 79:179–184. https://doi.org/10.1016/j.ijid.2018.11.371
National Institute of biomedical imaging and bioengineering. Drug delivery systems (2022). https://www.nibib.nih.gov/science-education/science-topics/drug-delivery-systems-getting-drugs-their-targets-controlled-manner#:~:text=Medications%20can%20be%20taken%20in,the%20skin%2C%20or%20by%20injection
Nemmar A, Al-Salam S, Greish YE, Beegam S, Zaaba NE, Ali BH (2023) Impact of Intratracheal Administration of Polyethylene Glycol-Coated Silver Nanoparticles on the Heart of Normotensive and Hypertensive Mice. Int J Mol Sci 24(10):8890. https://doi.org/10.3390/ijms24108890
Nezami S, Sadeghi M, Mohajerani H (2020) A novel pH-sensitive and magnetic starch-based nanocomposite hydrogel as a controlled drug delivery system for wound healing. Polym Degrad Stab. https://doi.org/10.1016/j.polymdegradstab.2020.109
Nguyen TT, Ding D, Wolter WR, Perez RL, Champion MM, Mahasenan KV, Chang M (2018) Validation of matrix metalloproteinase-9 (MMP-9) as a novel target for treatment of diabetic foot ulcers in humans and discovery of a potent and selective small-molecule MMP-9 inhibitor that accelerates healing. J Med Chem. https://doi.org/10.1021/acs.jmedchem.8b01005
Nicoletti G, Tresoldi MM, Malovini A, Visaggio M, Faga A, Scevola S (2018) Versatile use of dermal substitutes: a retrospective survey of 127 consecutive cases. Indian J Plast Surg 51(01):046–053. https://doi.org/10.4103/ijps.IJPS_217_17
Niu J, Yuan M, Gao P, Wang L, Qi Y, Chen J, Liu X (2023) Microemulsion-Based Keratin-Chitosan Gel for Improvement of Skin Permeation/Retention and Activity of Curcumin. Gels 9(7):587. https://doi.org/10.3390/gels9070587
Noore S, Rastogi NK, O’Donnell C, Tiwari B (2021) Novel Bioactive Extraction and Nano-Encapsulation. Encyclopedia 1(3):632–664. https://doi.org/10.3390/encyclopedia1030052
Nosrati H, Aramideh Khouy R, Nosrati A, Khodaei M et al (2021) Nanocomposite scaffolds for accelerating chronic wound healing by enhancing angiogenesis. J Nanobiotechnol 19(1):1–21. https://doi.org/10.1186/s12951-020-00755-7
Okur ME, Karantas ID, Senyigit Z, Okur NU, Siafaka PI (2020) Recent trends on wound management: New therapeutic choices based on polymeric carriers. Asian J Pharm Sci 15(6):661–684. https://doi.org/10.1016/j.ajps.2019.11.008
Omidian H, Wilson RL, Chowdhury SD (2023) Enhancing Therapeutic Efficacy of Curcumin: Advances in Delivery Systems and Clinical Applications. Gels (basel, Switzerland) 9(8):596. https://doi.org/10.3390/gels9080596
Onyekwelu I, Yakkanti R, Protzer L, Pinkston CM, Tucker C, Seligson D (2017) Surgical wound classification and surgical site infections in the orthopaedic patient. J Am Acad Orthop Surg Glob Res Rev. https://doi.org/10.5435/JAAOSGlobal-D-17-00022
Opneja A, Kapoor S, Stavrou EX (2019) Contribution of platelets, the coagulation and fibrinolytic systems to cutaneous wound healing. Thromb Res 179:56–63. https://doi.org/10.1016/j.thromres.2019.05.001
Ozcan Bülbul E, Ustundag Okur N, Mısırlı D, Cevher E, Tsanaktsis V, Bingol Ozakpınar O, Siafaka PI (2023) Applying quality by design approach for the determination of potent paclitaxel loaded poly (lactic acid) based implants for localized tumor drug delivery. Int J Polymeric Mater Polymeric Biomater 72(12):968–983. https://doi.org/10.1080/00914037.2022.2067538
Pakolpakcıl A, Osman B, Goktalay G, Ozer ET, Sahan Y, Becerir B, Karaca E (2021) Design and in vivo evaluation of alginate-based pH-sensing electrospun wound dressing containing anthocyanins. J Polym Res 28:1–13. https://doi.org/10.1007/s10965-020-02400-1
Papaneophytou C, Katsipis G, Halevas E, Pantazaki AA (2019) Polyhydroxyalkanoates applications in drug carriers. Biotechnol Appl. https://doi.org/10.1007/978-981-13-3759-8_5
Park K (2014) Controlled drug delivery systems: past forward and future back. J Control Release 190:3–8. https://doi.org/10.1016/j.jconrel.2014.03.054
Patil PB, Uphade KB, Saudagar RB (2018) A REVIEW: OSMOTIC DRUG DELIVERY SYSTEM. Pharma Sci Monitor 9:2
Pawar R, Pathan A, Nagaraj S, Kapare H, Giram P, Wavhale R (2023) Polycaprolactone and its derivatives for drug delivery. Polym Adv Technol 34(10):3296–3316. https://doi.org/10.1002/pat.6140
Phan S, Feng CH, Huang R, Lee ZX, Moua Y, Phung OJ, Lenhard JR (2023) Relative Abundance and Detection of Pseudomonas aeruginosa from Chronic Wound Infections Globally. Microorganisms 11:1210. https://doi.org/10.3390/microorganisms11051210
Pourhajibagher M, Pourakbari B, Bahador A (2022) Contribution of antimicrobial photo-sonodynamic therapy in wound healing: An in vivo effect of curcumin-nisin-based poly (L-lactic acid) nanoparticle on Acinetobacter baumannii biofilms. BMC Microbiol 22(1):1–16. https://doi.org/10.1186/s12866-022-02438-9
Pourseif T, Ghafelehbashi R, Abdihaji M, Radan N, Kaffash E, Heydari M, Ren Q (2023) Chitosan-based nanoniosome for potential wound healing applications: Synergy of controlled drug release and antibacterial activity. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2023.123185
Prajapati VD, Maheriya PM (2019) Hyaluronic acid as potential carrier in biomedical and drug delivery applications. Funct Polysacch Biomed Applicat. https://doi.org/10.1016/B978-0-08-102555-0.00007-8
Prakash P, Lee WH, Loo CY, Wong HSJ, Parumasivam T (2022) Advances in Polyhydroxyalkanoate Nanocarriers for Effective Drug Delivery: An Overview and Challenges. Nanomaterials (basel, Switzerland) 12(1):175. https://doi.org/10.3390/nano12010175
Puca V, Marulli RZ, Grande R, Vitale I, Niro A, Molinaro G, Prezioso S, Muraro R, Di Giovanni P (2021) Microbial Species Isolated from Infected Wounds and Antimicrobial Resistance Analysis: Data Emerging from a Three-Years Retrospective Study. Antibiotics 10(10):1162. https://doi.org/10.3390/antibiotics10101162
Qin S, Xiao W, Zhou C, Pu Q, Deng X, Lan L, Liang H, Song X, Wu M (2022) Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics. Signal Transduct Target Ther 7(1):199. https://doi.org/10.1038/s41392-022-01056-1
Quispe MM, Villanueva ME, Copello GJ, Lopez OV, Villar MA (2023) Films of Poly (Hydroxybutyrate)(PHB) and Copper with Antibacterial Activity. Polym 15(13):2907. https://doi.org/10.3390/polym15132907
Raizman R, Little W, Smith AC (2021) Rapid Diagnosis of Pseudomonas aeruginosa in Wounds with Point-Of-Care Fluorescence Imaing. Diagnostics (basel, Switzerland) 11(2):280. https://doi.org/10.3390/diagnostics11020280
Ramasamy T, Ruttala HB, Gupta B, Poudel BK, Choi HG, Yong CS, Kim JO (2017) Smart chemistry-based nanosized drug delivery systems for systemic applications: a comprehensive review. J Control Release 258:226–253. https://doi.org/10.1016/j.jconrel.2017.04.043
Ramirez-Acuna JM, Cardenas-Cadena SA, Marquez-Salas PA, Garza-Veloz I, Perez-Favila A, Cid-Baez MA, Flores-Morales V, Martinez-Fierro ML (2019) Diabetic Foot Ulcers: Current Advances in Antimicrobial Therapies and Emerging Treatments. Antibiotics (basel, Switzerland) 8(4):193. https://doi.org/10.3390/antibiotics8040193
Raziyeva K, Kim Y, Zharkinbekov Z, Kassymbek K, Jimi S, Saparov A (2021) Immunology of acute and chronic wound healing. Biomol 11(5):700
Ren Q, Chan KW, Huang H, Wang Z, Fang X et al (2020) Platelet-derived alpha-granules are associated with inflammation in patients with NK/T-cell lymphoma-associated hemophagocytic syndrome. Cytokine. https://doi.org/10.1016/j.cyto.2019.154878
Ren Z, Duan Z, Zhang Z, Fu R, Zhu C, Fan D (2023) Instantaneous self-healing and strongly adhesive self-adaptive hyaluronic acid-based hydrogel for controlled drug release to promote tendon wound healing. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2023.125001
Rezaie HR, Esnaashary M, Aref A, arjmand, Ochsner A, (2018) A Review of Biomaterials and Their Applications in Drug Delivery. Springer, Singapore, pp 1–8
Rice JB, Desai U, Cummings AK, Birnbaum HG, Skornicki M, Parsons NB (2014) Burden of diabetic foot ulcers for Medicare and private insurers. Diabetes Care 37(3):651–658. https://doi.org/10.2337/dc13-2176
Rijal BP, Satyal D, Parajuli NP (2017) High Burden of Antimicrobial Resistance among Bacteria Causing Pyogenic Wound Infections at a Tertiary Care Hospital in Kathmandu. Nepal J Pathogens. https://doi.org/10.1155/2017/9458218
Rodrigues M, Kosaric N, Bonham CA, Gurtner GC (2019) Wound healing: a cellular perspective. Physiol Rev 99(1):665–706. https://doi.org/10.1152/physrev.00067.2017
Roy S, Santra S, Das A, Dixith S, Sinha M, Ghatak S, Sen CK (2020) Staphylococcus aureus Biofilm Infection Compromises Wound Healing by Causing Deficiencies in Granulation Tissue Collagen. Ann Surg 271(6):1174–1185. https://doi.org/10.1097/SLA.0000000000003053
Ruamsap N, Thomas CS, Imerbsin R, Reed MC, Gonwong S, Lurchachaiwong W, Demons ST (2023) Chronic Wound Infection Model of Acinetobacter baumannii in Outbred Mice. Mil Med 188(7–8):e1708–e1716. https://doi.org/10.1093/milmed/usac020
Rubalskii E, Ruemke S, Salmoukas C, Aleshkin A, Bochkareva S, Modin E, Haverich A (2019) Fibrin glue as a local drug-delivery system for bacteriophage PA5. Sci Rep 9(1):2091. https://doi.org/10.1038/s41598-018-38318-4
Ruivo J, Francisco C, Oliveira R, Figueiras A (2015) The main potentialities of resveratrol for drug delivery systems. Braz J Pharm Sci 51:499–513. https://doi.org/10.1590/S1984-82502015000300002
Sabacinski KA, Kaufman JL (2018) U.S. Patent Application No. 15/789,066
Sabbagh F, Kim BS (2022) Recent advances in polymeric transdermal drug delivery systems. J Control Release 341:132–146. https://doi.org/10.1016/j.jconrel.2021.11.025
Saghazadeh S, Rinoldi C, Schot M, Kashaf SS, Sharifi F, Jalilian E, Nuutila K, Giatsidis G, Mostafalu P et al (2018) Drug delivery systems and materials for wound healing applications. Adv Drug Deliv Rev 127:138–166. https://doi.org/10.1016/j.addr.2018.04.008
Sandomierski M, Chojnacka M, Ratajczak M, Voelkel A (2023) Zeolites with Divalent Ions as Carriers in the Delivery of Epigallocatechin Gallate. ACS Biomater Sci Eng 9(9):5322–5331. https://doi.org/10.1021/acsbiomaterials.3c00599
Sathiyaseelan A, Saravanakumar K, Zhang X, Naveen KV, Wang MH (2023) Ampicillin-resistant bacterial pathogens targeted chitosan nano-drug delivery system (CS-AMP-P-ZnO) for combinational antibacterial treatment. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2023.124129
Sawaya AP, Stone RC, Brooks SR, Pastar I, Jozic I et al (2020) Deregulated immune cell recruitment orchestrated by FOXM1 impairs human diabetic wound healing. Nat Commun 11(1):4678. https://doi.org/10.1038/s41467-020-18276-0
Schwendeman SP, Shah RB, Bailey BA, Schwendeman AS (2014) Injectable controlled release depots for large molecules. J Control Release 190:240–253. https://doi.org/10.1016/j.jconrel.2014.05.057
Seavey JG, Masters ZA, Balazs GC, Tintle SM, Sabino J, Fleming ME, Valerio IL (2016) Use of a bioartificial dermal regeneration template for skin restoration in combat casualty injuries. Regen Med 11(1):81–90. https://doi.org/10.2217/rme.15.83
Sedighim S, Chen Y, Xu C, Mohindra R, Liu H, Agrawal DK, Thankam FG (2023) Carboxymethyl cellulose–alginate interpenetrating hydroxy ethyl methacrylate crosslinked polyvinyl alcohol reinforced hybrid hydrogel templates with improved biological performance for cardiac tissue engineering. Biotechnol Bioeng 120(3):819–835. https://doi.org/10.1002/bit.28291
Semwal R, Joshi SK, Semwal RB, Semwal DK (2023) Recent Developments and Potential for Clinical Use of Casein as a Drug Carrier. Curr Drug Deliv. https://doi.org/10.2174/1567201819666220513085552
Sen CK (2019) Human wounds and its burden: an updated compendium of estimates. Adv Wound Care 8(2):39–48. https://doi.org/10.1089/wound.2019.0946
Sepulveda AF, Kumpgdee-Vollrath M, Franco MK, Yokaichiya F, de Araujo DR (2023) Supramolecular structure organization and rheological properties modulate the performance of hyaluronic acid-loaded thermosensitive hydrogels as drug-delivery systems. J Colloid Interface Sci 630:328–340. https://doi.org/10.1016/j.jcis.2022.10.064
Seraphim PM, Leal EC, Moura J, Gonçalves P, Gonçalves JP, Carvalho E (2020) Lack of lymphocytes impairs macrophage polarization and angiogenesis in diabetic wound healing. Life Sci. https://doi.org/10.1016/j.lfs.2020.117813
Shah SA, Sohail M, Khan S, Minhas MU, De Matas M, Sikstone V, Kousar M (2019) Biopolymer-based biomaterials for accelerated diabetic wound healing: A critical review. Int J Biol Macromol 139:975–993. https://doi.org/10.1016/j.ijbiomac.2019.08.007
Shah SA, Sohail M, Khan SA, Kousar M (2021) Improved drug delivery and accelerated diabetic wound healing by chondroitin sulfate grafted alginate-based thermoreversible hydrogels. Mater Sci Eng C. https://doi.org/10.1016/j.msec.2021.112169
Sharma R, Sharma KS, Kumar D (2022) Introduction to Nanotechnology. Nanomaterials in Clinical Therapeutics: Synthesis and Applications 1–31
Shende P, Gupta H (2020) Formulation and comparative characterization of nanoparticles of curcumin using natural, synthetic and semi-synthetic polymers for wound healing. Life Sci. https://doi.org/10.1016/j.lfs.2020.117588
Shevelev AB, La Porta N, Isakova EP, Martens S, Biryukova YK, Belous AS, Deryabina YI (2020) In vivo antimicrobial and wound-healing activity of resveratrol, dihydroquercetin, and dihydromyricetin against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Pathogens. https://doi.org/10.3390/pathogens9040296
Shi L, Zhang J, Zhao M, Tang S, Cheng X, Zhang W, Wang Q (2021) Effects of polyethylene glycol on the surface of nanoparticles for targeted drug delivery. Nanoscale 13(24):10748–10764. https://doi.org/10.1039/d1nr02065j
Siepmann J, Siegel RA, Rathbone MJ (2012) Fundamentals and applications of controlled release drug delivery (Vol. 3, pp. 33–34)
Simman R, Mari W, Younes S, Wilson M (2018) Use of hyaluronic acid–based biological bilaminar matrix in wound bed preparation: A case series. Eplasty 18:e17
Singh AV, Gemmati D, Kanase A, Pandey I, Misra V, Kishore V, Bill J (2018) Nanobiomaterials for vascular biology and wound management: A review. Veins Lymphat. https://doi.org/10.4081/vl.2018.7196
Smith R, Russo J, Fiegel J, Brogden N (2020) Antibiotic delivery strategies to treat skin infections when innate antimicrobial defense fails. Antibiotics. https://doi.org/10.3390/antibiotics9020056
Snippert HJ, Haegebarth A, Kasper M, Jaks V, van Es JH, Barker N, Clevers H (2010) Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science 327(5971):1385–1389. https://doi.org/10.1126/science.1184733
Soni V, Pandey V, Asati S, Gour V, Tekade RK (2019) Biodegradable block copolymers and their applications for drug delivery. In Basic Fundamentals of Drug Delivery (pp. 401–447)
Spadari CC, Lanser DM, Araujo MV, De Jesus DF, Lopes LB, Gelli A, Ishida K (2023) Oral delivery of brain-targeted miltefosine-loaded alginate nanoparticles functionalized with polysorbate 80 for the treatment of cryptococcal meningitis. J Antimicrob Chemother 78(4):1092–1101. https://doi.org/10.1093/jac/dkad053
Sun M, Xie Q, Cai X, Liu Z, Wang Y, Dong Z, Xu Y (2020) Preparation and characterization of epigallocatechin gallate, ascorbic acid, gelatin, chitosan nanoparticles and their beneficial effect on wound healing of diabetic mice. Int J Biol Macromol 148:777–784. https://doi.org/10.1016/j.ijbiomac.2020.01.198
Taghe S, Mirzaeei S, Bagheri M (2023) Preparation of Polycaprolactone and Polymethacrylate Nanofibers for Controlled Ocular Delivery of Ketorolac tromethamine: Pharmacokinetic study in Rabbit’s Eye. Eur J Pharm Sci. https://doi.org/10.1016/j.ejps.2023.106631
Taheri P, Jahanmardi R, Koosha M, Abdi S (2020) Physical, mechanical and wound healing properties of chitosan/gelatin blend films containing tannic acid and/or bacterial nanocellulose. Int J Biol Macromol 154:421–432. https://doi.org/10.1016/j.ijbiomac.2020.03.114
Takeo M, Lee W, Ito M (2015) Wound healing and skin regeneration. Cold Spring Harb Perspect Med. https://doi.org/10.1101/cshperspect.a023267
Tan SY, Leung Z, Wu AR (2020) Recreating Physiological Environments In Vitro: Design Rules for Microfluidic-Based Vascularized Tissue Constructs. Small. https://doi.org/10.1002/smll.201905055
Tan S, Han J, Yuan X, Song Z, Gao L, Gao J, Wang L (2023) Epigallocatechin gallate-loaded pH-responsive dressing with effective antioxidant, antibacterial and anti-biofilm properties for wound healing. Mater Des. https://doi.org/10.1016/j.matdes.2023.111701
Teixeira MO, Antunes JC, Felgueiras HP (2021) Recent advances in fiber–hydrogel composites for wound healing and drug delivery systems. Antibiotics 10(3):248
Tian J, Jiang F, Zeng Q, PourhosseiniAsl M, Han C, Ren K (2023) Biocompatible Piezoelectric Polymer Poly (Lactic Acid)-Based Stethoscope for Wearable Health Monitoring Devices. IEEE Sensors J 23(6):6264–6271. https://doi.org/10.1109/JSEN.2023.3240120
Tiwari R, Pathak K (2023) Local Drug Delivery Strategies towards Wound Healing. Pharmaceutics 15(2):634. https://doi.org/10.3390/pharmaceutics15020634
Tomic-Canic M, Burgess JL, O’Neill KE, Strbo N, Pastar I (2020) Skin microbiota and its interplay with wound healing. Am J Clin Dermatol 21(1):36–43. https://doi.org/10.1007/s40257-020-00536-w
Tyler B, Gullotti D, Mangraviti A, Utsuki T, Brem H (2016) Polylactic acid (PLA) controlled delivery carriers for biomedical applications. Adv Drug Deliv Rev 107:163–175. https://doi.org/10.1016/j.addr.2016.06.018
Uehara M, Li X, Sheikhi A, Zandi N, Walker B, Saleh B, Abdi R (2019) Anti-IL-6 eluting immunomodulatory biomaterials prolong skin allograft survival. Sci Rep 9(1):6535. https://doi.org/10.1038/s41598-019-42349-w
Uttayarat P, Chiangnoon R, Thongnopkoon T, Noiruksa K, Trakanrungsie J, Phattanaphakdee W, Athikomkulchai S (2023) Electron Beam Irradiation Cross-Linked Hydrogel Patches Loaded with Red Onion Peel Extract for Transdermal Drug Delivery: Formulation, Characterization, Cytocompatibility, and Skin Permeation. Gels 9(1):52. https://doi.org/10.3390/gels9010052
Vargason AM, Anselmo AC, Mitragotri S (2021) The evolution of commercial drug delivery technologies. Nat Biomed Eng 5:951–967. https://doi.org/10.1038/s41551-021-00698-w
Veith AP, Henderson K, Spencer A, Sligar AD, Baker AB (2019) Therapeutic strategies for enhancing angiogenesis in wound healing. Adv Drug Deliv Rev 146:97–125. https://doi.org/10.1016/j.addr.2018.09.010
Vestby LK, Grønseth T, Simm R, Nesse LL (2020) Bacterial Biofilm and its Role in the Pathogenesis of Disease. Antibiotics (basel, Switzerland) 9(2):59. https://doi.org/10.3390/antibiotics9020059
Vidallon MLP, Teo BM (2020) Recent developments in biomolecule-based nanoencapsulation systems for antimicrobial delivery and biofilm disruption. Chem Commun 56(90):13907–13917. https://doi.org/10.1039/d0cc05880g
Vieira IRS, Tessaro L, Lima AKO, Velloso IPS, Conte-Junior CA (2023) Recent Progress in Nanotechnology Improving the Therapeutic Potential of Polyphenols for Cancer. Nutrients 15(14):3136. https://doi.org/10.3390/nu15143136
Virzì NF, Fallica AN, Romeo G, Greish K, Alghamdi MA, Patanè S, Pittalà V (2023) Curcumin I-SMA nanomicelles as promising therapeutic tool to tackle bacterial infections. RSC Adv 13(44):31059–31066. https://doi.org/10.1039/D3RA04885C
Wadhwa K, Kadian V, Puri V, Bhardwaj BY, Sharma A, Pahwa R, Singh I (2022) New insights into quercetin nanoformulations for topical delivery. Phytomed plus. https://doi.org/10.1016/j.phyplu.2022.100257
Wang S, Zhang J, Chen M, Wang Y (2013) Delivering flavonoids into solid tumors using nanotechnologies Expert Opin. Drug Deliv 10(10):1411–1428. https://doi.org/10.1517/17425247.2013.807795
Wang PH, Huang BS, Horng HC, Yeh CC, Chen YJ (2018) Wound healing. J Chin Med Assoc 81(2):94–101. https://doi.org/10.1016/j.jcma.2017.11.002
Wang W, Lu Kj YuCh et al (2019) Nano-drug delivery systems in wound treatment and skin regeneration. J Nanobiotechnol 17:82. https://doi.org/10.1186/s12951-019-0514-y
Wang Y, Shi Z, Sun Y, Wu X, Li S, Dong S, Lan T (2020) Preparation of amphiphilic magnetic polyvinyl alcohol targeted drug carrier and drug delivery research. Designed Monomers Polym 23(1):197–206. https://doi.org/10.1080/15685551.2020.1837442
Wang Y, Kankala RK, Ou C, Chen A, Yang Z (2022) Advances in hydrogel-based vascularized tissues for tissue repair and drug screening. Bioact Mater 9:198–220
Wang X, Peng Y, Wu Y, Cao S, Deng H, Cao Z (2023) Chitosan/silk fibroin composite bilayer PCL nanofibrous mats for bone regeneration with enhanced antibacterial properties and improved osteogenic potential. Int J Biol Macromol. https://doi.org/10.1016/j.ijbiomac.2023.123265
Wang K, Cai X, Rao Y, Liu L, Hu Z, Peng H, Shang W (2024) GehB Inactivates Lipoproteins to Delay the Healing of Acute Wounds Infected with Staphylococcus aureus. Curr Microbiol 81(1):36. https://doi.org/10.1007/s00284-023-03550-3
Wani SUD, Veerabhadrappa GH (2018) Silk Fibroin Based Drug Delivery Applications: Promises and Challenges. Curr Drug Targets 19(10):1177–1190. https://doi.org/10.2174/1389450119666171227205525
Watcharajittanont N, Tabrizian M, Ekarattanawong S, Meesane J (2023) Bone-mimicking scaffold based on silk fibroin incorporated with hydroxyapatite and titanium oxide as enhanced osteo-conductive material for bone tissue formation: fabrication, characterization, properties, and in vitro testing. Biomed Mater. https://doi.org/10.1088/1748-605X/acf542
Wei Q, Ma L, Zhang W, Ma G, Hu Z (2022) EGCG-crosslinked carboxymethyl chitosan-based hydrogels with inherent desired functions for full-thickness skin wound healing. J Mater Chem B 10(20):3927–3935. https://doi.org/10.1039/D2TB00074A
Wilkinson HN, Hardman MJ (2020) Wound healing: Cellular mechanisms and pathological outcomes. Open Biol. https://doi.org/10.1098/rsob.200223
Wojcik M, Kazimierczak P, Benko A, Palka K, Vivcharenko V, Przekora A (2021) Superabsorbent curdlan-based foam dressings with typical hydrocolloids properties for highly exuding wound management. Mater Sci Eng C. https://doi.org/10.1016/j.msec.2021.112068
Wong FSY, Tsang KK, Chan BP, Lo ACY (2023) Both non-coated and polyelectrolytically-coated intraocular collagen-alginate composite gels enhanced photoreceptor survival in retinal degeneration. Biomater. https://doi.org/10.1016/j.biomaterials.2022.121948
Wu J, Li X, Li D, Ren X, Li Y, Herter EK, Landen NX (2020a) MicroRNA-34 family enhances wound inflammation by targeting LGR4. J Invest Dermatol 140(2):465–476. https://doi.org/10.1016/j.jid.2019.07.694
Wu J, Zhang Z, Zhou W, Liang X, Zhou G, Han CC, Liu Y (2020b) Mechanism of a long-term controlled drug release system based on simple blended electrospun fibers. J Control Release 320:337–346. https://doi.org/10.1016/j.jconrel.2020.01.020
Wu M, Chen J, Huang W, Yan B et al (2020c) Injectable and self-healing nanocomposite hydrogels with ultrasensitive pH-responsiveness and tunable mechanical properties: implications for controlled drug delivery. Biomacromol 21(6):2409–2420. https://doi.org/10.1021/acs.biomac.0c00347
Wu Z, Shi J, Song P, Li J, Cao S (2021) Chitosan/hyaluronic acid based hollow microcapsules equipped with MXene/gold nanorods for synergistically enhanced near infrared responsive drug delivery. Int J Biol Macromol 183:870–879. https://doi.org/10.1016/j.ijbiomac.2021.04.164
Xian C, Zhang Z, You X, Fang Y, Wu J (2022) Nanosized fat emulsion injection modulating local microenvironment promotes angiogenesis in chronic wound healing. Adv Funct Mater 32(32):2202410. https://doi.org/10.1002/adfm.202202410
Xu Y, Kim CS, Saylor DM, Koo D (2017) Polymer degradation and drug delivery in PLGA-based drug–polymer applications: A review of experiments and theories. J Biomed Mater Res B Appl Biomater 105(6):1692–1716. https://doi.org/10.1002/jbm.b.33648
Xu W, Dielubanza E, Maisel A, Leung K, Mustoe T, Hong S, Galiano R (2021) Staphylococcus aureus impairs cutaneous wound healing by activating the expression of a gap junction protein, connexin-43 in keratinocytes. Cell Mol Life Sci 78(3):935–947. https://doi.org/10.1007/s00018-020-03545-4
Xu Z, Liu G, Li Q et al (2022) A novel hydrogel with glucose-responsive hyperglycemia regulation and antioxidant activity for enhanced diabetic wound repair. Nano Res 15(5305):5315. https://doi.org/10.1007/s12274-022-4192-y
Yadav D, Dewangan HK (2021) PEGYLATION: an important approach for novel drug delivery system. J Biomater Sci Polym Ed 32(2):266–280. https://doi.org/10.1080/09205063.2020.1825304
Yang J, Chen Z, Pan D, Li H, Shen J (2020) Umbilical cord-derived mesenchymal stem cell-derived exosomes combined pluronic F127 hydrogel promote chronic diabetic wound healing and complete skin regeneration. Int J Nanomed. https://doi.org/10.2147/IJN.S249129
Zahariev N, Draganova M, Zagorchev P, Pilicheva B (2023) Casein-Based Nanoparticles: A Potential Tool for the Delivery of Daunorubicin in Acute Lymphocytic Leukemia. Pharmaceutics 15(2):471. https://doi.org/10.3390/pharmaceutics15020471
Zhang M, Xu C, Liu D, Han MK, Wang L, Merlin D (2018) Oral delivery of nanoparticles loaded with ginger active compound, 6-shogaol, attenuates ulcerative colitis and promotes wound healing in a murine model of ulcerative colitis. J Crohn’s Colitis 12(2):217–229. https://doi.org/10.1093/ecco-jcc/jjx115
Zhang W, Qi X, Zhao Y, Liu Y, Xu L, Song X, Hou M (2020) Study of injectable Blueberry anthocyanins-loaded hydrogel for promoting full-thickness wound healing. Int J Pharm. https://doi.org/10.1016/j.ijpharm.2020.119543
Zhang R, Nie T, Fang Y, Huang H, Wu J (2021) Poly (disulfide) s: from synthesis to drug delivery. Biomacromol 23(1):1–19. https://doi.org/10.1021/acs.biomac.1c01210
Zhang R, Nie T, Wang L, He D, Kang Y, Zhang C, Wu J (2023b) Facile synthesis of poly (disulfide) s through one-step oxidation polymerization for redox-responsive drug delivery. Biomater Sci 11(12):4254–4264. https://doi.org/10.1039/D3BM00461A
Zhang C, Shiqi HONG, Gokhale R, NG JY (2022) U.S. Patent Application No. 17/594,935
Zhang J, Wang L, Ding M, You X, Wu J, Pang J (2023) Impact of poly (ester amide) structure on properties and drug delivery for prostate cancer therapy. BME frontiers https://doi.org/10.34133/bmef.0025
Zhao X, Gu R, Zhao Y, Wei F, Gao X, Zhuang Y, Dai J (2023) Adult spinal cord tissue transplantation combined with local tacrolimus sustained-release collagen hydrogel promotes complete spinal cord injury repair. Cell Prolif. https://doi.org/10.1111/cpr.13451
Zhong H, Huang J, Luo M et al (2023) Near-field electrospun PCL fibers/GelMA hydrogel composite dressing with controlled deferoxamine-release ability and retiform surface for diabetic wound healing. Nano Res 16:599–612. https://doi.org/10.1007/s12274-022-4813-5
Zhou L, Cai L, Ruan H, Zhang L, Wang J, Jiang H, Chen J (2021) Electrospun chitosan oligosaccharide/polycaprolactone nanofibers loaded with wound-healing compounds of Rutin and Quercetin as antibacterial dressings. Int J Biol Macromol 183:1145–1154. https://doi.org/10.1016/j.ijbiomac.2021.05.031
Zhu S, Li H, Lyu H, Qian S (2021). Absorbable Hydrogel Skin Repair Scaffold Constructed on the Basis of Recombinant Human Collagen, Preparation Method and Use Method Thereof. CN Patent No. CN112717200B
Zugates GT, Rago A, Freyman T, Sharma U, Busold R, Caulkins J, Bonner DK. (2017) U.S. Patent No. 9,623,143. Washington, DC: U.S. Patent and Trademark Office
Acknowledgements
The authors are extremely thankful to the institution Karpagam Academy of Higher Education for their expertise and supporting facilities which helped in drafting this manuscript.
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study’s conception and design. The first author R.PR collected data and designed the manuscript and the second author M.K guided in framing the manuscript.
Corresponding author
Ethics declarations
Conflict of interests
The authors have no relevant financial or non-financial interests to disclose.
Ethical standard
Not applicable.
Additional information
Communicated by Yusuf Akhter.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Rathna, R.P., Kulandhaivel, M. Advancements in wound healing: integrating biomolecules, drug delivery carriers, and targeted therapeutics for enhanced tissue repair. Arch Microbiol 206, 199 (2024). https://doi.org/10.1007/s00203-024-03910-y
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00203-024-03910-y