Potential Wound Healing Applications Research Articles

Value-Added Nanocellulose Valorized from Fruit Peel Waste for Potential Dermal Wound Healing and Tissue Regenerative Applications

Value-Added Nanocellulose Valorized from Fruit Peel Waste for Potential Dermal Wound Healing and Tissue Regenerative Applications

Preparation of β-cyclodextrin derivatives/metamizole inclusion complex nanofibers: Characterization, drug release, and wound scratch assay

Nanofibrous wound dressings fabricated by electrospinning have attracted significant research interest as they enable the controlled release of active substances at the wound site. The development of electrospun nanofibers with anti-inflammatory drugs, which demonstrate great potential for wound healing applications, is one of the main focuses of present research efforts. In this study, nanofibrous webs of 2-hydroxypropyl-β-cyclodextrin (HPβCD) and methyl-β-cyclodextrin (MβCD) loaded with metamizole (MMS) were fabricated by electrospinning. The prepared nanofibers were characterized by field-emission scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, thermogravimetric/differential thermal analysis, 1H nuclear magnetic resonance spectroscopy, ultraviolet diffuse reflectance spectroscopy, and photoluminescence analysis. The interactions of HPβCD and MβCD with MMS in aqueous solutions were studied using absorption and fluorescence spectroscopy, and the 1:1 MMS/CD inclusion complexes were theoretically analyzed at the PM3 level of theory. Furthermore, the drug release, biocompatibility, and wound scratch assay of the nanofibers were evaluated. In vitro drug release analysis revealed controllable release of MMS from the nanofibers. The CD nanofibers loaded with MMS showed good biocompatibility with skin fibroblasts. An in vitro wound scratch assay indicated that the nanofibers promoted fast wound closure with a rate of 98.66 ± 3.9%. In summary, the prepared nanofibrous webs are promising candidates for wound-dressing applications.

Fabrication, Characterization of Curcumin Loaded Alginate Chitosan for Potential Wound Healing Applications

The most employed scaffolds in tissue engineering are alginate and chitosan due to their properties like biodegradability, compatibility, and structural similarity to that of the ECM. Curcumin, together with scaffolds such as alginate and chitosan, can improve wound healing properties by tissue repair and regeneration. This study aims to load curcumin into alginate chitosan scaffolds and to analyze their potential wound healing properties by characterization and checking their biocompatibility. Curcumin was loaded into the alginate-chitosan scaffold. It was then characterized using Fourier Transform-InfraRed (FT-IR) spectroscopy and Scanning Electron Microscopy (SEM). Annexin V PI apoptotic assay and Hemolytic assay were done to screen its biocompatibility. FT-IR has strong absorption bands at 3237, 2359, 1597, 1406, 1025, and 947 cm−1. SEM analysis of the curcumin-loaded alginate-chitosan scaffold showed the dispersed curcumin on the surface of the porous scaffold. Our results suggest that the curcumin-loaded alginate-chitosan scaffold possesses greater biocompatibility towards peripheral blood mononuclear cells (PBMC) which was confirmed by Annexin V - PI assay and hemolytic assay. Curcumin loaded onto an alginate-chitosan scaffold is reported to be biocompatible using flow cytometry and hemolytic assay. However a more detailed study must be done before using it for potential wound healing applications.

Laser deposited ultra-thin silver nanoparticles on CMC-PVA blend film as sheet for wound dressings

In this study, silver nanoparticles (AgNPs) were synthesized using pulsed laser deposition and deposited on a sheet film composed of Carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA), and AgNPs. These polymeric-based nano-composites were investigated for their potential application in wound healing. The structural properties of the composites were examined using X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). Morphological features were observed through field emission scanning electron microscopy (FESEM), and roughness characteristics were studied using FESEM micrographs. The CMC-PVA-AgNPs scaffolds with deposition times of 10 and 12.5 min showed minimal deviations in surface structure compared to the composites with longer deposition times, where scattered AgNPs and aggregates were observed. Furthermore, the roughness parameter (Ra) values indicated the potential of silver NPs in creating trapping sites and crystal defects, as evidenced by an increase in Ra from 18.96 nm in the pure CMC-PVA blend to 34.17 nm at a deposition time of 20 min. The optical properties of the composites were investigated by determining the band-gap of direct and indirect transition modes, which exhibited a decreasing trend. The presence of silver NPs was confirmed by the plasmon absorption band observed around 400 nm. The intensity of the plasmon peaks increased with longer laser deposition times, indicating an increase in the silver content over time. Finally, the antibacterial activity of the prepared scaffolds against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Micrococcusluteus was evaluated, and the results strongly support the potential of the prepared material for biological applications. In conclusion, the synthesized CMC-PVA-AgNPs nano-composites deposited using pulsed laser deposition technique exhibited promising properties for wound healing applications. The comprehensive characterization of the composites, including their structural, morphological, optical, and antibacterial properties, provides valuable insights for further research and development in the field of biomaterials.

Wound Dressing Based on Silver Nanoparticle Embedded Wool Keratin Electrospun Nanofibers Deposited on Cotton Fabric: Preparation, Characterization, Antimicrobial Activity, and Cytocompatibility.

Wool keratin (WK) protein is attractive for wound dressing and biomedical applications due to its excellent biodegradability, cytocompatibility, and wound-healing properties. In this work, WK-based wound dressings were prepared by depositing WK/poly(vinyl alcohol) (PVA) and silver nanoparticle (Ag NP)-embedded WK/PVA composite nanofibrous membranes on cotton fabrics by electrospinning. Ag NPs were biosynthesized by reduction and stabilization with sodium alginate. The formed Ag NPs were characterized by ultraviolet-visible and Fourier transform infrared (FTIR) spectroscopy, and their size was determined by transmission electron microscopy and image analysis. The formed Ag NPs were spherical and had an average diameter of 9.95 nm. The produced Ag NP-embedded WK/PVA composite nanofiber-deposited cotton fabric surface was characterized by FTIR and dynamic contact angle measurements, and the nanofiber morphologies were characterized by scanning electron microscopy. The average diameter of the nanofibers formed by 0.1% Ag NP-embedded WK/PVA solution was 146.7 nm. The antibacterial activity of the surface of cotton fabrics coated with electrospun composite nanofibers was evaluated against the two most common wound-causing pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. The cotton fabric coated with 0.1% Ag NP-embedded WK/PVA nanofibers showed very good antibacterial activity against both pathogens, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results showed good cytocompatibility against L-929 mouse fibroblast cells. However, the increase in Ag NP content in the nanofibers to 0.2% negatively affected the cell viability due to the high release rate of Ag ions. The results achieved show that the developed wound dressing has good potential for wound healing applications.

Surface slicing and toolpath planning for in-situ bioprinting of skin implants

Bioprinting has emerged as a successful method for fabricating engineered tissue implants, offering great potential for wound healing applications. This study focuses on an advanced surface-based slicing approach aimed at designing a skin implant specifically for in-situ bioprinting. The slicing step plays a crucial role in determining the layering arrangement of the tissue during printing. By utilizing surface slicing, a significant shift from planar fabrication methods is achieved. The developed methodology involves the utilization of a customized robotic printer to deliver biomaterials. A multilayer slicing and toolpath generation procedure is presented, enabling the fabrication of skin implants that incorporate the epidermal, dermal, and hypodermal layers. One notable advantage of using the approximate representation of the native wound site surface as the slicing surface is the avoidance of planar printing effects such as staircasing. This surface slicing method allows for the design of non-planar and ultra-thin skin implants, ensuring a higher degree of geometric match between the implant and the wound interface. Furthermore, the proposed methodology demonstrates superior surface quality of the in-situ bio-printed implant on a hand model, validating its ability to create toolpaths on implants with complex surfaces.

A dual network cross-linked hydrogel with multifunctional Bletilla striata polysaccharide/gelatin/tea polyphenol for wound healing promotion

Wound healing is a dynamic and complex biological process, and traditional biological excipients cannot meet the needs of the wound healing process, and there is an urgent need for a biological dressing with multifunctionality and the ability to participate in all stages of wound healing. This study developed tea polyphenol (TP) incorporated multifunctional hydrogel based on oxidized Bletilla striata polysaccharide (OBSP) and adipic acid dihydrazide modified gelatin (Gel-ADH) with antimicrobial, antioxidant hemostatic, and anti-inflammatory properties to promote wound healing. The composite OBSP, Gel-ADH, TP (OBGTP) hydrogels prepared by double crosslinking between OBSP, TP and Gel-ADH via Schiff base bonding and hydrogen bonding had good rheological and swelling properties. The introduction of TP provided the composite hydrogel with excellent antioxidant antibacterial activities against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coil). In the rat liver hemorrhage model and skin injury model, the OBGTP composite hydrogel had significant (p < 0.001) hemostatic ability, and had the ability to accelerate collagen deposition, reduce the expression of inflammatory factors, and promote rapid wound healing. In addition, OBGTP hydrogels had adhesive properties and good biocompatibility. In conclusion, OBGTP multifunctional composite hydrogels have great potential for wound healing applications.

Tetracycline hydrochloride loaded-alginate based nanoparticle-hydrogel beads for potential wound healing applications: In vitro drug delivery, release kinetics, and antibacterial activity

Novel hydrogel beads based on nanocomposite with outstanding antibacterial and swelling capabilities have been successfully produced as an efficient drug carrier for potential drug delivery systems in wound healing applications. The beads were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and EDX-Mapping analysis. Then, using tetracycline hydrochloride (TCH) as a model drug system, they were studied in vitro for their potential efficiency as pH and temperature dependent sustained drug delivery carriers. Moreover, they were assessed in terms of porosity, swelling degree, encapsulation efficiency, and in vitro release kinetics. Beads released drugs at their highest levels under alkaline circumstances (pH = 8) and at a temperature of 39 °C, with a cumulative TCH release of 96.2 % at 36 h and in accordance with the Weibull kinetics model (R2 = 0.98). Additionally, the disc diffusion experiment demonstrated the strong antibacterial activity of the synthesized beads and offered a feasible and cost-effective wound dressing material for treating infected wounds.

Cold Atmospheric Plasma: An Emerging Immunomodulatory Therapy

AbstractCold atmospheric plasma (CAP) is a novel technology that generates a unique combination of reactive oxygen and nitrogen species (ROS/RNS), electric fields, and UV radiation. CAP has shown promise in regulating the immune system and has potential clinical applications in wound healing, cancer treatment, and infection control. This review provides an overview of the immunological regulation activity of CAP, highlighting its substantial impact on cytokines production, immune cell phagocytosis, and immune cell proliferation. CAP has also been demonstrated to have potent therapeutic effect in anti‐inflammation, wound repair, viral and bacterial infections. Furthermore, CAP has been investigated as an adjuvant therapy for tumor treatment, eliciting a robust antitumor immune response and remarkable synergistic effects in diverse combination therapies. Further research is needed to fully understand the mechanisms underlying the effects of CAP on the immune system and to optimize its clinical application.

Pectin wrapped halloysite nanotube reinforced Polycaprolactone films for potential wound healing application

The current research work focuses on preparing the polycaprolactone (PCL) based nanocomposite films embedded with surface modified Halloysite Nanotube (HNT). The avenue of the study is to unravel the applicability of polymer nanocomposites for wound healing. The flexible property of HNT was taken as the major force to accomplish the addition of biopolymer pectin onto its surface. Functionalization of HNT with pectin has certainly enhanced its binding nature with the polymer. The PCL nanocomposite films were characterized by several promising techniques such as FTIR, XRD, DSC-TGA, FESEM, TEM, AFM, and mechanical properties were too examined along. When compared to the plane PCL film, the nanocomposite films manifested favorable results in terms of mechanical and chemical properties. Additionally, biometric studies such as in-vitro swelling, enzymatic degradation, and hemolysis performed on the films gave extremely good results. The haemolytic percentage recorded for the films exhibited a steady decrease with increasing amount of nanofillers. The MTT assay showed cell proliferation and its increase as the embedded HNT is more in the matrix. Wound closure study performed on NIH3T3 cell line with 1, 3 and 5wt% of films has given a strong proof for the involvement of polymer and HNT in the healing procedure.

Clinical applications of exosomes in cosmetic dermatology

AbstractIntroductionExosomes are extracellular vesicles that transport bioactive substances during normal and abnormal cellular physiological processes. The unique properties of exosomes can be exploited for use as biomarkers and targeted drug delivery vehicles, and are, for this reason, gaining increasing attention in the field of dermatology. This review aims to synthesise the existing evidence supporting exosomes in regenerative and cosmetic dermatology.MethodA comprehensive PubMed search for the period of 2010–2023 was performed using the MeSH terms "exosome" and "skin.” The initial search yielded 246 studies, which were then refined to 178 studies following title and abstract screening. Studies were confined to human or animal studies published in English that evaluated the use of exosomes in medical/cosmetic dermatology. A subsequent full‐text review based on these criteria yielded 34 studies, which were then reviewed.ResultsExosomes can be derived from a variety of biological sources and show potential application in wound healing, scar prophylaxis, photodamage prevention, skin regeneration, improved grafting success, hair loss mitigation, and as biomarkers and drug carriers.ConclusionExosomes are gaining traction in regenerative and cosmetic dermatology. However, their widespread clinical application is hindered by cost, a complex isolation process, lack of uniform protocols, limited assessment of infective potential, and a paucity of clinical evidence. Further research in this area is needed, especially by way of clinical studies evaluating the efficacy of exosome‐based treatments on human skin.

CO2-Mediated Alkali-Neutralization Curdlan Hydrogels for Potential Wound Healing Application.

Physical hydrogels of natural polysaccharides are considered as ideal candidates for wound dressing due to their natural biological activity and no harmful cross-linking agents. However, it remains a challenge to fabricate such hydrogel dressings in a facile and low-cost way. Herein, we reported an easy and cost-effective method to construct CO2-mediated alkali-neutralization Curdlan (CR) hydrogels without using an external cross-linking agent. Two types of hydrogels (denoted as CR-NaOH and CR-Na3PO4, respectively) were fabricated by dissolving CR powders in a NaOH or Na3PO4 aqueous solution, followed by keeping the CR alkaline solutions in air. The obtained pure CR hydrogels possessed a tunable porous structure with walls containing different forms of nanofibrils. These hydrogels exhibited much higher gel strength by comparison with the gels prepared by conventional heating treatment. They were flexible, stretchable, twistable, and conformable to arbitrarily curved skins. Moreover, they exhibited ideal swellability, proper degradability, and water vapor transmission rate, and their physicochemical properties were closely related to CR concentration in the alkaline solution. These two hydrogels also supported the growth of L929 cells. Importantly, studies on wound healing revealed that both 3CR-NaOH and 3CR-Na3PO4 hydrogels were capable of accelerating the wound healing process through recruiting more macrophages/fibroblasts, inducing more collagen deposition and neovascularization (α-SMA and CD31) without carrying any exogenous bioactive components. In conclusion, the present work not only reported promising materials for application in wound therapy but also offered a facile and safe manufacturing procedure for generating pure CR physical hydrogels with better performance.

Antimicrobial characteristics of the Li2O–ZrO2–Si2O bioactive glass and glass‐ceramic for bone regeneration and wound healing

AbstractInfections cause significant complications in surgical cases involving fractures and implants. Biomaterials, particularly bioactive glass, are known for their biocompatibility and tissue regeneration potential. The integration of bactericidal properties with bioactive glasses could prove pivotal in preventing infections during bone and wound regeneration. The LZS (Li2O–ZrO2–Si2O) glass system, recognized for its potential for bone regeneration via scaffolds, is a candidate for further exploration of its antimicrobial capabilities. This study evaluated the antimicrobial properties of LZS bioactive glass and glass‐ceramic against various pathogens (Staphylococcus aureus, Escherichia coli, Candida albicans, Pseudomonas aeruginosa, and Salmonella enteritidis) using the spread‐plate method. The LZS glass exhibited antibacterial effects against all the tested microorganisms, with minimum bactericidal concentrations (MBC) varying between 50 and 150 mg/mL. The bactericidal effects of the biomaterials were attributed to ion release from the glass matrix, which increased the pH of the solution and effectively eliminated microorganisms. In addition, this study found no evidence of DNA damage, and the LZS systems exhibited no cytotoxic or genotoxic effects at the tested concentrations. The results showed that the investigated antibacterial glass and glass‐ceramic have potential applications in bone regeneration or wound healing, especially in scenarios where bacterial proliferation is a concern.

Suppression of SOCS3 expression in macrophage cells: Potential application in diabetic wound healing

Impaired polarization of M1 to M2 macrophages has been reported in diabetic wounds. We aimed to improve this polarization by down-regulation of expression of the “Suppressor of Cytokine Signaling 3” (SOCS3) gene in macrophages. Two oligodeoxynucleotide (ASO) sequences were designed against SOC3 mRNA and were loaded to mannosylated-polyethyleneimine (Man-PEI). The optimum N/P ratio for Man-PEI-ASO was determined to be 8 based on loading efficiency, particle size, zeta potential, cellular uptake and cytotoxicity assay. pH stability of ASO in Man-PEI-ASO and its protection from DNase I was confirmed. After in vitro treatment of macrophages with Man-PEI-ASO, SOCS3 was downregulated, SOCS1 upregulated, and SOCS1/SOCS3 ratio increased. Also, expressions of macrophage markers of M2 (IL-10, Arg1, CD206) increased and those of M1 (IL-1β, NOS2, CD68) decreased, and secretion of pro-inflammatory cytokines (TNF-α and IL-1β) decreased while that of anti-inflammatory cytokine IL-4 increased. All suggested a polarization into M2 phenotype. Finally, the Man-PEI-ASO was loaded in hydrogel and applied to a diabetic wound model in mice. It improved the healing to the level observed in non-diabetic wounds. We show that using antisense sequences against SOC3 mRNA, macrophage polarization could be directed into the M2 phenotype and healing of diabetic wound could be highly improved.

Bilayer regenerated cellulose/quaternized chitosan-hyaluronic acid/collagen electrospun scaffold for potential wound healing applications

In this study, a bilayer electrospun scaffold has been prepared using regenerated cellulose (RC)/quaternized chitosan (CS) as the primary layer and collagen/hyaluronic acid (HA) as the second layer. An approximate 48 mol% substituted (estimated from 1H NMR) quaternized CS was used in this study. Both layers were crosslinked with EDC/NHS, reflecting an increase in UTS (2.29 MPa for the bilayer scaffold compared to 1.82 MPa for the RC scaffold). Initial cell viability, cell adhesion and proliferation, FDA staining for live cells, and hydroxyproline release rate from cells were evaluated with L929 mouse fibroblast cells. Also, detailed in vitro studies were performed using HADF cells, which include MTT Assay, Live/Dead imaging, DAPI staining, gene expression of PDGF, VEGF-A, and COL1 in RT-PCR, and cell cycle analysis. The collagen/HA-based bilayer scaffold depicted a 9.76-fold increase of VEGF-A compared to a 2.1-fold increase for the RC scaffold, indicating angiogenesis and vascularization potential. In vitro scratch assay was performed to observe the migration of cells in simulated wounds. Antimicrobial, antioxidant, and protease inhibitory activity were further performed, and overall, the primary results highlighted the potential usage of bilayer scaffold in wound healing applications.

Insights into optimizing exosome therapies for acute skin wound healing and other tissue repair.

Exosome therapy holds great promise as a novel approach to improve acute skin wound healing. This review provides a comprehensive overview of the current understanding of exosome biology and its potential applications in acute skin wound healing and beyond. Exosomes, small extracellular vesicles secreted by various stem cells, have emerged as potent mediators of intercellular communication and tissue repair. One advantage of exosome therapy is its ability to avoid potential risks associated with stem cell therapy, such as immune rejection or stem cells differentiating into unwanted cell types. However, further research is necessary to optimize exosome therapy, not only in the areas of exosome isolation, characterization, and engineering, but also in determining the optimal dose, timing, administration, and frequency of exosome therapy. Thus, optimization of exosome therapy is critical for the development of more effective and safer exosome-based therapies for acute skin wound healing and other diseases induced by cancer, ischemia, or inflammation. This review provides valuable insights into the potential of exosome therapy and highlights the need for further research to optimize exosome therapy for clinical use.

Antioxidant, antibacterial and biodegradable hydrogel films from carboxymethyl tragacanth gum and clove extract: Potential for wound dressings application

Bioactive films based on sodium carboxymethyl tragacanth gum (CMT) and polyvinyl alcohol (PVA) enriched with clove extract (CE) for potential wound healing applications were fabricated by the solution casting method. The fabricated films were characterized by FTIR, XRD, EDX, SEM, and TGA analyses. The XRD pattern of CMT/PVA/CE5 % showed an amorphous structure with broad peaks, suggesting that the presence of CE led to a reduction in crystallinity and an increase in amorphousness in the polymer film. The fabricated films showed a high water absorption capacity and swelled up to 80 % over 24 h for the CMT/PVA/CE5 % formulation crosslinked with 15 % citric acid. Excellent biodegradability with 88 % was observed in soil over 40 days for CMT/PVA/CE5 %. The presence of CE in CMT/PVA improved the antioxidant activity by up to 92 % within 30 min. Strong antibacterial effects of CMT/PVA/CE5 % film were observed against Salmonella enterica and Staphylococcus aureus, with inhibition zone diameters of 20 mm and 18 mm, respectively. Across concentrations from 25 to 600 μg/mL, CMT/PVA/CE5 % films displayed over 80 % cell viability on cultured human dermal fibroblasts after 48 h. The results indicated that CMT/PVA/CE5 % bioactive film can be employed as effective, non-toxic wound dressings with infection prevention and healing promotion capabilities.

Biobran-loaded core/shell nanofibrous scaffold: a promising wound dressing candidate.

This research examined the effectiveness of Biobran as a bioactive substance that could potentially improve wound healing. It also looked at how Biobran affects the properties of a nanofibrous scaffold made through coaxial electrospinning. This is the first study exploring the use of Biobran in this context and its interaction with nanofibrous scaffolds. The scaffolds were composed of poly(ε-caprolactone) (PCL) in the shell and various concentrations of Biobran blended with polyvinyl alcohol (PVA) in the core. The properties of the scaffolds were characterized by SEM, TEM, FTIR, XRD, TGA, DSC, stress-strain test, WCA, release test, MTT cytotoxicity assay, wound scratching assay, and the dye exclusion method using trypan blue. The scaffolds loaded with Biobran exhibited a more compact and smooth morphology compared with the scaffold without Biobran. The physical interaction and crystallinity of the polymers in the scaffolds were also affected by Biobran in a concentration-dependent manner. This positively influenced their tensile strength, elongation at break, thermal stability, and hydrophilicity. The porosity, water uptake capacity, and WVTR of the nanofibrous scaffolds are within the optimal ranges for wound healing. The release rate of Biobran, which revealed a biphasic release pattern, decreased with increasing Biobran concentration, resulting in controlled and sustained delivery of Biobran from the nanofiber scaffolds. The cell viability assays showed a dose-dependent effect of Biobran on WISH cells, which might be attributed to the positive effect of Biobran on the physicochemical properties of the nanofibrous scaffolds. These findings suggest that Biobran-loaded core/shell nanofiber scaffolds have a potential application in wound healing as an ideal multifunctional wound dressing.

Innovative wound management: creating dynamic Alg-Mg/SF hydrogels for controlled Mg2+ release in wound healing.

Antibacterial hydrogels have gained considerable attention for soft tissue repair, particularly in preventing infections associated with wound healing. However, developing an antibacterial hydrogel that simultaneously possesses excellent cell affinity and controlled release of metal ions remains challenging. This study introduces an antibacterial hydrogel based on alginate modified with bisphosphonate, forming a coordination complex with magnesium ions. The hydrogel, through an interpenetrating network with silk fibroin, effectively controls the release of magnesium ions and enhances strain resistance. The Alg-Mg/SF hydrogel not only demonstrates outstanding biocompatibility and broad-spectrum antibacterial properties but also stimulates macrophages to secrete anti-inflammatory factors. This advanced Alg-Mg/SF hydrogel provides a convenient therapeutic approach for chronic wound management, showcasing its potential applications in wound healing and other relevant biomedical fields.

Biodegradable polyester copolymers: synthesis based on the Biginelli reaction, characterization, and evaluation of their application properties.

The Biginelli reaction, a three-component cyclocondensation reaction, is an important member of the multicomponent reaction (MCR) family. In this study, we conducted end-group modifications on a variety of biodegradable polyesters, including poly(1,4-butylene adipate) (PBA), poly(ε-caprolactone) (PCL), polylactic acid (PLA), and poly(p-dioxanone) (PPDO), based on the precursor polyethylene glycol (PEG). By combining two polymers through the Biginelli multi-component reaction, four new biodegradable polyester copolymers, namely DHPM-PBA, DHPM-PCL, DHPM-PLA, and DHPM-PPDO, were formed. These Biginelli reactions demonstrated exceptional completeness, validating the efficiency of the synthesis strategy. Although the introduction of various polyesters lead to different properties, such as crystallinity and cytotoxicity, the newly synthesized 3,4-dihydro-2(H)-pyrimidinone compounds (DHPMs) exhibit enhanced hydrophilicity and can self-assemble in water and N,N-dimethylformamide (DMF) solution to form micelles with a controllable size. Furthermore, DHPM-PPDO promotes cellular growth and has potential applications in wound healing and tissue engineering. In conclusion, this method demonstrates great universality and methodological significance and offers insights into the medical applications of polyethylene glycol.