Boosting antitumor efficacy using docetaxel-loaded nanoplatforms: from cancer therapy to regenerative medicine approaches.

The intersection of nanotechnology and pharmacology has revolutionized the delivery and efficacy of chemotherapeutic agents, notably docetaxel, a key drug in cancer treatment. Traditionally limited by poor solubility and significant side effects, docetaxel's therapeutic potential has been significantly enhanced through its incorporation into nanoplatforms, such as nanofibers and nanoparticles. This advancement offers targeted delivery, controlled release, and improved bioavailability, dramatically reducing systemic toxicity and enhancing patient outcomes. Nanofibers provide a versatile scaffold for the controlled release of docetaxel, utilizing techniques like electrospinning to tailor drug release profiles. Nanoparticles, on the other hand, enable precise drug delivery to tumor cells, minimizing damage to healthy tissues through sophisticated encapsulation methods such as nanoprecipitation and emulsion. These nanotechnologies not only improve the pharmacokinetic properties of docetaxel but also open new avenues in regenerative medicine by facilitating targeted therapy and cellular regeneration. This narrative review highlights the transformative impact of docetaxel-loaded nanoplatforms in oncology and beyond, showcasing the potential of nanotechnology to overcome the limitations of traditional chemotherapy and pave the way for future innovations in drug delivery and regenerative therapies. Through these advancements, nanotechnology promises a new era of precision medicine, enhancing the efficacy of cancer treatments while minimizing adverse effects.

Anticarcinogenic impact of extracellular vesicles (exosomes) from cord blood stem cells in malignant melanoma: A potential biological treatment.

Incidence of Malignant Melanoma has become the 5th in the UK. To date, the major anticancer therapeutics include cell therapy, immunotherapy, gene therapy and nanotechnology-based strategies. Recently, extracellular vesicles, especially exosomes, have been highlighted for their therapeutic benefits in numerous chronic diseases. Exosomes display multifunctional properties, including inhibition of cancer cell proliferation and initiation of apoptosis. In the present in vitro study, the antitumour effect of cord blood stem cell (CBSC)-derived exosomes was confirmed by the CCK-8 assay (p < 0.05) on CHL-1 melanoma cells and improve the repair mechanism on lymphocytes from melanoma patients. Importantly, no significant effect was observed in healthy lymphocytes when treated with the exosome concentrations at 24, 48 and 72 h. Comet assay results (OTM and %Tail DNA) demonstrated that the optimal exosome concentration showed a significant impact (p < 0.05) in lymphocytes from melanoma patients whilst causing no significant DNA damage in lymphocytes of healthy volunteers was 300 µg/ml. Similarly, the Comet assay results depicted significant DNA damage in a melanoma cell line (CHL-1 cells) treated with CBSC-derived exosomes, both the cytotoxicity of CHL-1 cells treated with CBSC-derived exosomes exhibited a significant time-dependent decrease in cell survival. Sequencing analysis of CBSC exosomes showed the presence of the let-7 family of miRNAs, including let-7a-5p, let-7b-5p, let-7c-5p, let-7d-3p, let-7d-5p and two novel miRNAs. The potency of CBSC exosomes in inhibiting cancer progression in lymphocytes from melanoma patients and CHL-1 cells whilst causing no harm to the healthy lymphocytes makes it a potential candidate as an anticancer therapy.

A Natural Hydrogel with Prohealing Properties Enhances Tendon Regeneration.

Tendon regeneration and reduction of peritendinous adhesion remain major clinical challenges. This study addresses these challenges by adopting a unique hydrogel derived from the skin secretion of Andrias davidianus (SSAD) and taking advantage of its biological effects, adhesiveness, and controllable microstructures. The SSAD-derived hydrogel contains many cytokines, which could promote tendon healing. In vitro, leach liquid of SSAD powder could promote tendon stem/progenitor cells migration. In vivo, the SSAD-derived hydrogel featuring double layers possesses strong adhesiveness and could reconnect ruptured Achilles tendons of Sprague-Dawley rats without suturing. The intimal SSAD-derived hydrogel, with a pore size of 241.7 ± 21.0 µm, forms the first layer of the hydrogel to promote tendon healing, and the outer layer SSAD-derived hydrogel, with a pore size of 3.3 ± 1.4 µm, reducing peritendinous adhesion by serving as a dense barrier. Additionally, the SSAD-derived hydrogel exhibits antioxidant and antibacterial characteristics, which further contribute to the reduction of peritendinous adhesion. In vivo studies suggest that the SSAD-derived hydrogel reduces peritendinous adhesion, increases collagen fiber deposition, promotes cell proliferation, and improves the biomechanical properties of the regenerated tendons, indicating better functional restoration. The SSAD-derived bilayer hydrogel may be a feasible biomaterial for tendon repair in the future.

Efficacy of mesenchymal stromal cells and cellular products in improvement of symptoms for COVID-19 and similar lung diseases.

At the end of 2019, respiratory coronavirus diseases 2019 (COVID-19) appeared and spread rapidly in the world. Besides several mutations, the outcome of this pandemic was the death up to 15% of hospitalized patients. Mesenchymal stromal cell therapy as a therapeutic strategy seemed successful in treatment of several diseases. Not only mesenchymal stromal cells of several tissues, but also their secreted extracellular vesicles and even secretome indicated beneficial therapeutic function. All of these three options were studied for treatment of COVID-19 as well as those respiratory diseases that have similar symptom. Fortunately, most of the outcomes were promising and optimistic. In this paper, we review in-vivo and clinical studies which have been used different sources of mesenchymal stromal cell, secreted extracellular vesicles, and secretome to improve and treat symptoms of COVID-19 and similar lung diseases.

The versatile biomedical applications of bismuth-based nanoparticles and composites: therapeutic, diagnostic, biosensing, and regenerative properties.

Studies of nanosized forms of bismuth (Bi)-containing materials have recently expanded from optical, chemical, electronic, and engineering fields towards biomedicine, as a result of their safety, cost-effective fabrication processes, large surface area, high stability, and high versatility in terms of shape, size, and porosity. Bi, as a nontoxic and inexpensive diamagnetic heavy metal, has been used for the fabrication of various nanoparticles (NPs) with unique structural, physicochemical, and compositional features to combine various properties, such as a favourably high X-ray attenuation coefficient and near-infrared (NIR) absorbance, excellent light-to-heat conversion efficiency, and a long circulation half-life. These features have rendered bismuth-containing nanoparticles (BiNPs) with desirable performance for combined cancer therapy, photothermal and radiation therapy (RT), multimodal imaging, theranostics, drug delivery, biosensing, and tissue engineering. Bismuth oxyhalides (BiOx, where X is Cl, Br or I) and bismuth chalcogenides, including bismuth oxide, bismuth sulfide, bismuth selenide, and bismuth telluride, have been heavily investigated for therapeutic purposes. The pharmacokinetics of these BiNPs can be easily improved via the facile modification of their surfaces with biocompatible polymers and proteins, resulting in enhanced colloidal stability, extended blood circulation, and reduced toxicity. Desirable antibacterial effects, bone regeneration potential, and tumor growth suppression under NIR laser radiation are the main biomedical research areas involving BiNPs that have opened up a new paradigm for their future clinical translation. This review emphasizes the synthesis and state-of-the-art progress related to the biomedical applications of BiNPs with different structures, sizes, and compositions. Furthermore, a comprehensive discussion focusing on challenges and future opportunities is presented.

Histatin peptides: Pharmacological functions and their applications in dentistry.

There are many human oral antimicrobial peptides responsible for playing important roles including maintenance, repairing of oral tissues (hard or soft) and defense against oral microbes. In this review we have highlighted the biochemistry, physiology and proteomics of human oral histatin peptides, secreted from parotid and submandibular salivary glands in human. The significance of these peptides includes capability for ionic binding that can kill fungal Candida albicans. They have histidine rich amino acid sequences (7-12 family members; corresponding to residues 12-24, 13-24, 12-25, 13-25, 5-11, and 5-12, respectively) for Histatin-3. However, Histatin-3 can be synthesized proteolytically from histatin 5 or 6. Due to their fungicidal response and high biocompatibility (little or no toxicity), these peptides can be considered as therapeutic agents with most probable applications for example, artificial saliva for denture wearers and salivary gland dysfunction conditions. The objectives of current article are to explore the human histatin peptides for its types, chemical and biological aspects. In addition, the potential for therapeutic bio-dental applications has been elaborated.

Effect of transforming growth factor-ß3 on mono and multilayer chondrocytes.

Articular cartilage is an avascular and flexible connective tissue found in joints. It produces a cushioning effect at the joints and provides low friction to protect the ends of the bones from wear and tear/damage. It has poor repair capacity and any injury can result pain and loss of mobility. Transforming growth factor-beta (TGF-ß), a cytokine superfamily, regulates cell function, including differentiation and proliferation. Although the function of the TGF-ßs in various cell types has been investigated, their function in cartilage repair is as yet not fully understood. The effect of TGF-ß3 in biological regulation of primary chondrocyte was investigated in this work. TGF-ß3 provided fibroblastic morphology to chondrocytes and therefore overall reduction in cell proliferation was observed. The length of the cells supplemented with TGF-ß3 were larger than the cells without TGF-ß3 treatment. This was caused by the fibroblast like cells (dedifferentiated chondrocytes) which occupied larger areas compared to cells without TGF-ß3 addition. The healing process of the model wound closure assay of chondrocyte multilayer was slowed down by TGF-ß3, and this cytokine negatively affected the strength of chondrocyte adhesion to the cell culture surface.

Effects of different transforming growth factor beta (TGF-ß) isomers on wound closure of bone cell monolayers.

This study aimed at determining the role of the transforming growth factor-beta (TGF-ß) isomers and their combinations in bone cell behaviour using MG63 cells. The work examined how TGF-ß1, 2 and 3 and their solvent and carrier (HCl and BSA, respectively) effected cell morphology, cell proliferation and integrin expression. This study also aimed at examining how the TGF-ßs and their solvent and carrier influenced wound closure in an in vitro wound closure model and how TGF-ßs influence extracellular matrix (ECM) secretion and integrin expression. The wound healing response in terms of healing rate to the TGF-ßs and their solvent/carrier was investigated in 300 µm ± 10-30 µm SD wide model wounds induced in fully confluent monolayers of MG63 bone cells. The effect of different TGF-ß isomers and their combinations on proliferation rate and cell length of human bone cells were also assessed. Immunostaining was used to determine if TGF-ßs modifies integrin expression and ECM secretion by the bone cells. Imaging with WSPR allowed observation of the focal contacts without the need for immunostaining. The wound healing results indicated that TGF-ß3 has a significant effect on the wound healing process and its healing rate was found to be higher than the control (p < 0.001), TGF-ß1 (p < 0.001), TGF-ß2 (p < 0.001), BSA/HCl (p < 0.001) and HCl (p < 0.001) in ascending order. It was also found that TGF-ß1 and TGF-ß2 treatment significantly improved wound closure rate in comparison to the controls (p < 0.001). All TGF-ß combinations induced a faster healing rate than the control (p < 0.001). It was expected that the healing rate following treatment with TGF-ß combinations would be greater than those healing rates following treatments with TGF-ß isomers alone, but this was not the case. The results also suggest that cell morphological changes were observed significantly more in cells treated with TGF-ß(2 + 3) and TGF-ß(1 + 3) (p < 0.001). Any cell treated with TGF-ß1, TGF-ß(1 + 2) and TGF-ß(1 + 2 + 3) showed significantly less elongation compared to the control and other TGF-ß isomers. In terms of proliferation rate, TGF-ß3 and TGF-ß(2 + 3) increased cell numbers more than TGF-ß1, TGF-ß2 and other combinations. TGF-ß1 and its combinations did not show significant proliferation and attachment compared to the control. Immunostaining indicated that treatment with TGF-ß3 significantly enhanced the secretion of collagen type I, fibronectin and integrins α3 and ß1. The WSPR experiments also indicated that TGF-ßs influenced the distribution of focal contacts. In conclusion, combining TGF-ß3 with any other TGF-ß isomer resulted in a faster model wound closure rate (p < 0.001), while treatment with TGF-ß1 in any TGF-ß combination reduced the healing rate (p < 0.001). It can therefore be concluded that the presence of TGF-ß1 has an inhibitory effect on bone wound healing while TGF-ß3 had the opposite effect and increased the rate of wound closure in a 2 dimensional cell culture environment.

Pathogenesis of Common Ocular Diseases: Emerging Trends in Extracellular Matrix Remodeling.

The prevalence of visual impairments in human societies is worrying due to retinopathy complications of several chronic diseases such as diabetes, cardiovascular diseases, and many more that are on the rise worldwide. Since the proper function of this organ plays a pivotal role in people's quality of life, identifying factors affecting the development/exacerbation of ocular diseases is of particular interest among ophthalmology researchers. The extracellular matrix (ECM) is a reticular, three-dimensional (3D) structure that determines the shape and dimensions of tissues in the body. The ECM remodeling/hemostasis is a critical process in both physiological and pathological conditions. It consists of ECM deposition, degradation, and decrease/increase in the ECM components. However, disregulation of this process and an imbalance between the synthesis and degradation of ECM components are associated with many pathological situations, including ocular disorders. Despite the impact of ECM alterations on the development of ocular diseases, there is not much research conducted in this regard. Therefore, a better understanding in this regard, can pave the way toward discovering plausible strategies to either prevent or treat eye disorders. In this review, we will discuss the importance of ECM changes as a sentimental factor in various ocular diseases based on the research done up to now.

Articular Cartilage Injury; Current Status and Future Direction.

Today, treatments of cartilage and osteochondral lesions are routine clinical procedures. The avascular and hard-to-self-repair nature of cartilage tissue has posed a clinical challenge for the replacement and reconstruction of damaged cartilage. Treatment of large articular cartilage defects is technically difficult and complex, often accompanied by failure. Articular cartilage cannot repair itself after injury due to a lack of blood vessels, lymph, and nerves. Various treatments for cartilage regeneration have shown encouraging results, but unfortunately, none have been the perfect solution. New minimally invasive and effective techniques are being developed. The development of tissue engineering technology has created hope for articular cartilage reconstruction. This technology mainly supplies stem cells with various sources of pluripotent and mesenchymal stem cells. This article describes the treatments in detail, including types, grades of cartilage lesions, and immune mechanisms in cartilage injuries.

Impacts of SARS-CoV-2 on brain renin angiotensin system related signaling and its subsequent complications on brain: A theoretical perspective.

Cellular ACE2 (cACE2), a vital component of the renin-angiotensin system (RAS), possesses catalytic activity to maintain AngII and Ang 1-7 balance, which is necessary to prevent harmful effects of AngII/AT2R and promote protective pathways of Ang (1-7)/MasR and Ang (1-7)/AT2R. Hemostasis of the brain-RAS is essential for maintaining normal central nervous system (CNS) function. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral disease that causes multi-organ dysfunction. SARS-CoV-2 mainly uses cACE2 to enter the cells and cause its downregulation. This, in turn, prevents the conversion of Ang II to Ang (1-7) and disrupts the normal balance of brain-RAS. Brain-RAS disturbances give rise to one of the pathological pathways in which SARS-CoV-2 suppresses neuroprotective pathways and induces inflammatory cytokines and reactive oxygen species. Finally, these impairments lead to neuroinflammation, neuronal injury, and neurological complications. In conclusion, the influence of RAS on various processes within the brain has significant implications for the neurological manifestations associated with COVID-19. These effects include sensory disturbances, such as olfactory and gustatory dysfunctions, as well as cerebrovascular and brain stem-related disorders, all of which are intertwined with disruptions in the RAS homeostasis of the brain.

Effect of TGF-ß3 on wound healing of bone cell monolayer in static and hydrodynamic shear stress conditions.

Introduction: Wound healing is characterized as a complicated and sophisticated biological process through which tissue heals and repairs itself after injury. However, the normal wound healing process relies on different growth factors as well as the presence of an accurate cytokine level to ensure appropriate cellular responses. In the case of wound healing, the effects of various growth factors have been studied, but the effects of transforming growth factor beta (TGF-ß) on wound healing have been found to be more significant because of its broad spectrum of impacts on healing the wounded tissues or skins. Methods: In the current study, the impact of TGF-ß3 in bone cells' wound healing was examined in vitro. Furthermore, the activities and characteristics of TGF-ß3, as well as those of related growth factors throughout this wound healing process, were studied under hydrodynamic shear stress conditions as well as static conditions of cultured bone cells. Results: We demonstrated that a positive outcome of TGF-ß3 treatment was found after 24 h under a static condition, while TGF-ß3 treatment was found to be effective under a dynamic condition for wound closure. In the case of the dynamic condition, a full wound closure was obtained after 18 h in both the control and TGF-ß3 treatment, while in the case of static conditions, wounds were found to remain open, even after 24 h, for both the control and TGF-ß3 treatment. Additionally, in the static condition, the wound closure rate with TGF-ß3 treatment was found to be quicker than that of the control flask, which implies that wound healing can be postponed in the static condition. In the dynamic condition, the wound healing process became more rapid in a cultured cell environment. Conclusion: The synergistic effect of TGF-ß3 and hydrodynamic shear stress conditions had a positive impact on increasing wound healing and improving the rate of wound closure.

Retinal Tissue Engineering: Regenerative and Drug Delivery Approaches.

In recent decades, the improvement of photoreceptor-cell transplantation has been used as an effective therapeutic approach to treat retinal degenerative diseases. In this review, the effect of different factors on the differentiation process and stem cells toward photoreceptors along with cell viability, morphology, migration, adhesion, proliferation, and differentiation efficiency is discussed. Scientists are researching to better recognize the reasons for retinal degeneration, as well as discovering novel therapeutic methods to restore lost vision. In this field, several procedures and treatments in the implantation of stem cells-derived retinal cells have been explored for clinical trials. However, the number of these clinical trials is too small to draw sound decisions about whether stem-cell therapies can offer a cure for retinal diseases. Nevertheless, future research directions have started for patients affected by retinal degeneration and promising findings have been obtained.

Recent Emerging Trend in Stem Cell Therapy Risk Factors.

Different types of stem cells have remarkable characteristics such as high proliferation rate, multi/pluripotency, self-renewal, and broad differentiation that can effectively treat diseases, cancers, and damage. Despite abundant therapeutic applications of stem cells in medical science, numerous risks threaten stem cell transplantation. Tumor development, immune response, cellular senescence, dosage effects, and administration timing are critical risks that should be considered in stem cell therapy. Hence, an investigation of possible risks is required before utilizing stem cell-based medicinal products in the clinical phase and human trials. This review aims to survey the literature and perspectives on the advantages and risks associated with pluripotent and multipotent stem cells.

Reconstruction of Critical Sized Maxillofacial Defects Using Composite Allogeneic Tissue Engineering: Systematic Review of Current Literature.

The current review aimed to assess the reliability and efficacy of tissue-engineered composite grafts in the reconstruction of large maxillofacial defects resulting from trauma or a benign pathologic disease. A systematic review of the literature was conducted using PubMed/Medline, Embase, and Scopus up to March 2022. The eligibility criteria included patients who had been treated with composite allogeneic tissue engineering for immediate/delayed reconstruction of large maxillofacial defects with minimum/no bone harvesting site. In the initial search, 2614 papers were obtained, and finally, 13 papers were eligible to be included in the current study. Most included papers were case reports or case series. A total of 144 cases were enrolled in this systematic review. The mean age of the patients was 43.34 (age range: 9-89). Most studies reported a successful outcome. Bone tissue engineering for the reconstruction and regeneration of crucial-sized maxillofacial defects is an evolving science still in its infancy. In conclusion, this review paper and the current literature demonstrate the potential for using large-scale transplantable, vascularized, and customizable bone with the aim of reconstructing the large maxillofacial bony defects in short-term follow-ups.

Role of Polymers in Microfluidic Devices.

Polymers are sustainable and renewable materials that are in high demand due to their excellent properties. Natural and synthetic polymers with high flexibility, good biocompatibility, good degradation rate, and stiffness are widely used for various applications, such as tissue engineering, drug delivery, and microfluidic chip fabrication. Indeed, recent advances in microfluidic technology allow the fabrication of polymeric matrix to construct microfluidic scaffolds for tissue engineering and to set up a well-controlled microenvironment for manipulating fluids and particles. In this review, polymers as materials for the fabrication of microfluidic chips have been highlighted. Successful models exploiting polymers in microfluidic devices to generate uniform particles as drug vehicles or artificial cells have been also discussed. Additionally, using polymers as bioink for 3D printing or as a matrix to functionalize the sensing surface in microfluidic devices has also been mentioned. The rapid progress made in the combination of polymers and microfluidics presents a low-cost, reproducible, and scalable approach for a promising future in the manufacturing of biomimetic scaffolds for tissue engineering.

Bioprinted Membranes for Corneal Tissue Engineering: A Review.

Corneal transplantation is considered a convenient strategy for various types of corneal disease needs. Even though it has been applied as a suitable solution for most corneal disorders, patients still face several issues due to a lack of healthy donor corneas, and rejection is another unknown risk of corneal transplant tissue. Corneal tissue engineering (CTE) has gained significant consideration as an efficient approach to developing tissue-engineered scaffolds for corneal healing and regeneration. Several approaches are tested to develop a substrate with equal transmittance and mechanical properties to improve the regeneration of cornea tissue. In this regard, bioprinted scaffolds have recently received sufficient attention in simulating corneal structure, owing to their spectacular spatial control which produces a three-cell-loaded-dimensional corneal structure. In this review, the anatomy and function of different layers of corneal tissue are highlighted, and then the potential of the 3D bioprinting technique for promoting corneal regeneration is also discussed.

Commercialization and regulation of regenerative medicine products: Promises, advances and challenges.

The ultimate goal of regenerative medicine is to repair, regenerate, or reconstruct functional loss in failed tissues and/or organs. Although regenerative medicine is a relatively new field, multiple diverse research groups are helping regenerative medicine reach its objectives. All endeavors in this field go through in silico, in vitro, in vivo, and clinical trials which are prerequisites to translating such approaches from the bench to the bedside. However, despite such promise, there are only a few regenerative medicine approaches that have actually entered commercialization due to extensive demands for the inclusion of multiple rules, principles, and finances, to reach the market. This review covers the commercialization of regenerative medicine, including its progress (or lack thereof), processes, regulatory concerns, and immunological considerations to name just a few key areas. Also, commercially available engineered tissues, including allografts, synthetic substitutes, and 3D bioprinting inks, along with commercially available cell and gene therapeutic products, are reviewed. Clinical applications and future perspectives are stated with a clear road map for improving the regenerative medicine field.

Investigation of Cell Adhesion and Cell Viability of the Endothelial and Fibroblast Cells on Electrospun PCL, PLGA and Coaxial Scaffolds for Production of Tissue Engineered Blood Vessel.

Endothelialization of artificial scaffolds is considered an effective strategy for increasing the efficiency of vascular transplantation. This study aimed to compare the biophysical/biocompatible properties of three different biodegradable fibrous scaffolds: Poly (ɛ-caprolactone) (PCL) alone, Poly Lactic-co-Glycolic Acid (PLGA) alone (both processed using Spraybase® electrospinning machine), and Coaxial scaffold where the fiber core and sheath was made of PCL and PLGA, respectively. Scaffold structural morphology was assessed by scanning electron microscope and tensile testing was used to investigate the scaffold tension resistance over time. Biocompatibility studies were carried out with human umbilical vein endothelial cells (HUVEC) and human vascular fibroblasts (HVF) for which cell viability (and cell proliferation over a 4-day period) and cell adhesion to the scaffolds were assessed by cytotoxicity assays and confocal microscopy, respectively. Our results showed that all biodegradable polymeric scaffolds are a reliable host to adhere and promote proliferation in HUVEC and HVF cells. In particular, PLGA membranes performed much better adhesion and enhanced cell proliferation compared to control in the absence of polymers. In addition, we demonstrate here that these biodegradable membranes present improved mechanical properties to construct potential tissue-engineered vascular graft.

Fabrication of 3D hybrid scaffold by combination technique of electrospinning-like and freeze-drying to create mechanotransduction signals and mimic extracellular matrix function of skin.

Fabrication of extracellular matrix (ECM)-like scaffolds (in terms of structural-functional) is the main challenge in skin tissue engineering. Herein, inspired by macromolecular components of ECM, a novel hybrid scaffold suggested which includes silk/hyaluronan (SF/HA) bio-complex modified by PCP: [polyethylene glycol/chitosan/poly(ɛ-caprolactone)] copolymer containing collagen to differentiate human-adipose-derived stem cells into keratinocytes. In followed by, different weight ratios (wt%) of SF/HA (S1:100/0, S2:80/20, S3:50/50) were applied to study the role of SF/HA in the improvement of physicochemical and biological functions of scaffolds. Notably, the combination of electrospinning-like and freeze-drying methods was also utilized as a new method to create a coherent 3D-network. The results indicated this novel technique was led to ~8% improvement of the scaffold's ductility and ~17% decrease in mean pore diameter, compared to the freeze-drying method. Moreover, the increase of HA (>20wt%) increased porosity to 99%, however, higher tensile strength, modulus, and water absorption% were related to S2 (38.1, 0.32 MPa, 75.3%). More expression of keratinocytes along with growth pattern similar to skin was also observed on S2. This study showed control of HA content creates a microporous-environment with proper modulus and swelling%, although, the role of collagen/PCP as base biocomposite and fabrication technique was undeniable on the inductive signaling of cells. Such a scaffold can mimic skin properties and act as the growth factor through inducing keratinocytes differentiation.