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International Journal of Bioprinting                                   Biomaterials with antibacterial agents




            that attach to fibroblasts to promote their activity and   dressings that could improve wound healing by specifically
            proliferation, as well as to enhance the formation of   promoting  angiogenesis. In  the  context  of  utilizing
            collagen.  Additionally, Zhang  et  al.  studied  human   biomaterial for wound healing, fish collagen has been
            umbilical cord mesenchymal stem cells (hUC-MSCs) with   combined with bioactive glass loaded with copper/cobalt
            the objective of applying an  in situ injectable hydrogel   ions to form a microfibrous mat for treating diabetic lesions
            made of collagen type-I (Col) and sodium alginate (SA) for   in in vivo rabbit models. In combination, these materials
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            wound healing.  Through increased cell proliferation, re-  are capable of enhancing the angiogenesis mechanism
            epithelialization potential, collagen deposition, and tissue   through enhanced interaction between these materials and
            remodeling, SA/Col hydrogel loaded with hUC-MSCs   induction of transcription of several pro-angiogenic genes
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            was shown to considerably enhance wound closure. Also,   by stabilizing hypoxia-inducible factor-1 (HIF1).  In the
            the scaffold can mitigate inflammation as well as promote   course of chronic wound healing, this scaffold could boost
            angiogenesis by secreting more proangiogenic molecules   wound closure, angiogenesis, and the creation of ECM. On
            including transforming growth factor beta (TGF-β1) and   the other hand, Tan et al. investigated a novel composite
            vascular endothelial growth factor (VEGF). The ability   biomaterial for the treatment of diabetic wounds created
            to release pro-regenerative cytokines is regarded as the   in a model of rats. Collagen-binding domain and VEGF
            primary biological feature of mesenchymal stem cells   were combined to develop a collagen scaffold (as CBD-
            that underpins their ability to trigger wound healing,   VEGF) that allowed for the steady and gradual release
            as confirmed by Pittenger et al.  In another study, Kim   of VEGF. These are important pro-angiogenic factors
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            et al. investigated the impact of soluble silkworm gland   that are essential for the healing of wounds. This study
            hydrolysate (SSGH) combined with human collagen on rat   demonstrated that the CBD-VEGF scaffold boasted an
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            models of wound.  SSGH/collagen scaffolds were found   increased rate of angiogenesis, which was conducive to
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            to accelerate wound healing, when compared to control   cell migration and wound closure.  In another study of
            groups, by leveraging the fibroblast-proliferating and   pro-angiogenic qualities, Long et al. connected CBD-
            apoptosis-inhibiting features. This is achieved by enabling   SDF-1α (also referred to as cell-derived factor 1α) and
            cells to produce vital growth factors, which in turn increase   a fusion protein known for its role in homing signals to
            capillary and fibroblast proliferation. 69         endothelial progenitor cells, or EPCs, to the CBD-VEGF
                                                               fusion protein. A dual functional scaffold (CBD-SDF-
            4.3. Promoting angiogenesis                        1α and CBD-VEGF) administration showed accelerating
            Angiogenesis, referring to the formation of new blood   diabetic wound healing, as demonstrated by an in vivo test
            vessels from preexisting vessels, is a vital phase in wound   conducted on diabetic rat wound models. With all factors
            healing.   The  wound  healing  process  is  driven  and   considered, this scaffold can definitely aid in angiogenesis,
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            supported by oxygen, necessary nutrients, and bioactive   vessel repair, and diabetic wound healing process.
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            compounds that are supplied to the wound site by these
            newly created blood vessels.  The aberrant growth factor   4.4. Infection control
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            secretion pattern in chronic wounds causes a severe   Wound healing process may take longer time in the
            impairment to angiogenesis, which in turn leads to the   absence of the usual clinical signs of infection. The number
            creation of defective granulation tissue and prevents   of bacteria or species present, the host immune response,
            wound healing from advancing to the proliferative phase.   the pathogenicity of the organisms, and the synergistic
            The release of VEGF plays a huge role in the angiogenesis   interactions between various species all play a role in
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            mechanism. Low-oxygen circumstances known as hypoxia   the progression from wound colonization to infection.
            or other endogenous cues elicit cellular secretion of VEGF   The most accurate way to diagnose wound infections is
            during the initiation and signaling phases.  Furthermore,   through clinical means. Microbiological investigations are
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            interleukin (IL)-1α and IL-1β control angiogenesis   crucial for the management of clinically infected wounds
            and  vascular  permeability  through  signal  transduction   that do not improve with standard care, as well as for
                                                               wounds that do not heal despite showing signs of clinical
            pathways, frequently working in concert to enhance these   infection because they may be locally infected or severely
            processes.  Endothelial cells at the arteries are activated   colonized. 85,86  People who suffer from several inflammatory,
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            during this process when they migrate through the ECM   autoimmune, and hereditary skin disorders that impair
            toward the wound site under the guidance of the angiogenic   the skin’s capacity to function as an infection barrier are
            factor gradient. 80
                                                               also more likely to have reduced skin integrity. These
               Promoting angiogenesis is an important aspect of the   conditions include dermatitis, psoriasis, and eczema.
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            wound healing process, particularly for DFU. Numerous   The typical clinical signs and symptoms of infection in a
            investigations have been carried out to develop wound   wound include increased pain and exudates, which may


            Volume 10 Issue 4 (2024)                        95                                doi: 10.36922/ijb.3372
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