Genipin-Cross-Linked Silk Fibroin/Alginate Dialdehyde Hydrogel with Tunable Gelation Kinetics, Degradability, and Mechanical Properties: A Potential Candidate for Tissue Regeneration.

Genipin-cross-linked silk fibroin (SF) hydrogel is considered to be biocompatible and mechanically robust. However, its use remains a challenge for in situ forming applications due to its prolonged gelation process. In our attempt to facilitate the in situ fabrication of a genipin-mediated SF hydrogel, alginate dialdehyde (ADA) was utilized as a reinforcement template. Here, SF/ADA-based hydrogels with different compositions were synthesized covalently and ionically. Incorporating ADA into the SF hydrogel increased pore size (44.66-174.66 µm), porosity (61.59-80.40%), and the equilibrium swelling degree (7.60-30.17). Moreover, a wide range of storage modulus and compressive modulus were obtained by adjusting the proportions of SF and ADA networks within the hydrogel. The in vitro cell analysis using preosteoblast cells (MC3T3-E1) demonstrated the cytocompatibility of all hydrogels. Overall, the covalently and ionically cross-linked SF/ADA hydrogel represents a promising solution for in situ forming hydrogels for applications in tissue regeneration.

Quantum dots-ßcyclodextrin-histidine labeled human adipose stem cells-laden chitosan hydrogel for bone tissue engineering.

Mesenchymal stem cells with differentiation ability to diverse cells play a crucial role in tissue engineering. Tracking the fate of these cells during the regeneration of tissue helps to obtain more information about their function. In this study, histidine conjugated ß-cyclodextrin as a cell-penetrating carrier with drug loading ability was attached to QDs nanoparticle (QD-ßCD-His) for stem cell labeling. Traceability of QD-ßCD-His labeled human adipose stem cells (hASCs) was monitored in 2D cell culture and 3D temperature-sensitive chitosan hydrogel scaffold. Dexamethasone (Dex) as an osteoinductive drug was loaded into QD-ßCD-His nano-carrier (QD-ßCD-His@Dex) to induce bone differentiation of labeled cells. Overall results indicated that QD-ßCD-His@Dex is a promising dual-purpose nano-carrier for stem cell labeling with osteoinductive potential in cell therapy as well as tissue engineering scaffolds.

Reduction of marginal mass required for successful islet transplantation in a diabetic rat model using adipose tissue-derived mesenchymal stromal cells.

BACKGROUND AIMS: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs), widely known as multipotent progenitors, release several cytokines that support cell survival and repair. There are in vitro and in vivo studies reporting the regenerative role of AT-MSCs possibly mediated by their protective effects on functional islet cells as well as their capacity to differentiate into insulin-producing cells (IPCs). METHODS: On such a basis, our goal in the present study was to use three different models including direct and indirect co-cultures and islet-derived conditioned medium (CM) to differentiate AT-MSCs into IPCs and to illuminate the molecular mechanisms of the beneficial impact of AT-MSCs on pancreatic islet functionality. Furthermore, we combined in vitro co-culture of islets and AT-MSCs with in vivo assessment of islet graft function to assess whether co-transplantation of islets with AT-MSCs can reduce marginal mass required for successful islet transplantation and prolong graft function in a diabetic rat model. RESULTS: Our findings demonstrated that AT-MSCs are suitable for creating a microenvironment favorable for the repair and longevity of the pancreas ß cells through the improvement of islet survival and maintenance of cell morphology and insulin secretion due to their potent properties in differentiation. Most importantly, hybrid transplantation of islets with AT-MSCs significantly promoted survival, engraftment and insulin-producing function of the graft and reduced the islet mass required for reversal of diabetes. CONCLUSIONS: This strategy might be of therapeutic potential solving the problem of donor islet material loss that currently limits the application of allogeneic islet transplantation as a more widespread therapy for type 1 diabetes.

Cell laden hydrogel construct on-a-chip for mimicry of cardiac tissue in-vitro study.

Since the leading cause of death are cardiac diseases, engineered heart tissue (EHT) is one of the most appealing topics defined in tissue engineering and regenerative medicine fields. The importance of EHT is not only for heart regeneration but also for in vitro developing of cardiology. Cardiomyocytes could grow and commit more naturally in their microenvironment rather than traditional cultivation. Thus, this research tried to develop a set up on-a-chip to produce EHT based on chitosan hydrogel. Micro-bioreactor was hydrodynamically designed and simulated by COMSOL and produced via soft lithography process. Chitosan hydrogel was also prepared, adjusted, and assessed by XRD, FTIR and also its degradation rate and swelling ratio were determined. Finally, hydrogels in which mice cardiac progenitor cells (CPC) were loaded were injected into the micro-device chambers and cultured. Each EHT in every chamber was evaluated separately. Prepared EHTs showed promising results that expanded in them CPCs and work as an integrated syncytium. High cell density culture was the main accomplishment of this study.

A practical machine learning approach for predicting the quality of 3D (bio)printed scaffolds.

3D (Bio)printing is a highly effective method for fabricating tissue engineering scaffolds, renowned for their exceptional precision and control. Artificial intelligence (AI) has become a crucial technology in this field, capable of learning and replicating complex patterns that surpass human capabilities. However, the integration of AI in tissue engineering is often hampered by the lack of comprehensive and reliable data. This study addresses these challenges by providing one of the most extensive datasets on 3D-printed scaffolds. It provides the most comprehensive open-source dataset and employs various AI techniques, from unsupervised to supervised learning. This dataset includes detailed information on 1171 scaffolds, featuring a variety of biomaterials and concentrations-including 60 biomaterials such as natural and synthesized biomaterials, crosslinkers, enzymes, etc.-along with 49 cell lines, cell densities, and different printing conditions. We used over 40 machine learning and deep learning algorithms, tuning their hyperparameters to reveal hidden patterns and predict cell response, printability, and scaffold quality. The clustering analysis using KMeans identified five distinct ones. In classification tasks, algorithms such as XGBoost, Gradient Boosting, Extra Trees Classifier, Random Forest Classifier, and LightGBM demonstrated superior performance, achieving higher accuracy and F1 scores. A fully connected neural network with six hidden layers from scratch was developed, precisely tuning its hyperparameters for accurate predictions. The developed dataset and the associated code are publicly available onhttps://github.com/saeedrafieyan/MLATEto promote future research.

Fabrication of 3D chitosan/polyvinyl alcohol/brushite nanofibrous scaffold for bone tissue engineering by electrospinning using a novel falling film collector.

Despite its advantages, electrospinning has limited effectiveness in 3D scaffolding due to the high density of fibers it produces. In this research, a novel electrospinning collector was developed to overcome this constraint. An aqueous suspension containing chitosan/polyvinyl alcohol nanofibers was prepared employing a unique falling film collector. Suspension molding by freeze-drying resulted in a 3D nanofibrous scaffold (3D-NF). The mineralized scaffold was obtained by brushite deposition on 3D-NF using wet chemical mineralization by new sodium tripolyphosphate and calcium chloride dihydrate precursors. The 3D-NF was optimized and compared with the conventional electrospun 2D nanofibrous scaffold (2D-NF) and the 3D freeze-dried scaffold (3D-FD). Both minor fibrous and major freeze-dried pore shapes were present in 3D-NFs with sizes of 16.11-24.32 µm and 97.64-234.41 µm, respectively. The scaffolds' porosity increased by 53 % to 73 % compared to 2D-NFs. Besides thermal stability, mineralization improved the 3D-NF's ultimate strength and elastic modulus by 2.2 and 4.7 times, respectively. In vitro cell studies using rat bone marrow mesenchymal cells confirmed cell infiltration up to 290 µm and scaffold biocompatibility. The 3D-NFs given nanofibers and brushite inclusion exhibited considerable osteoinductivity. Therefore, falling film collectors can potentially be applied to prepare 3D-NFs from electrospinning without post-processing.

Polyethylenimine Inclusion to Develop Aqueous Alginate-Based Core-Shell Capsules for Biomedical Applications.

Aqueous core-shell structures can serve as an efficient approach that allows cells to generate 3D spheroids with in vivo-like cell-to-cell contacts. Here, a novel strategy for fabricating liquid-core-shell capsules is proposed by inverse gelation of alginate (ALG) and layer-by-layer (LbL) coating. We hypothesized that the unique properties of polyethylenimine (PEI) could be utilized to overcome the low structural stability and the limited cell recognition motifs of ALG. In the next step, alginate dialdehyde (ADA) enabled the Schiff-base reaction with free amine groups of PEI to reduce its possible toxic effects. Scanning electron microscopy and light microscopy images proved the formation of spherical hollow capsules with outer diameters of 3.0 ± 0.1 mm for ALG, 3.2 ± 0.1 mm for ALG/PEI, and 4.0 ± 0.2 mm for ALG/PEI/ADA capsules. The effective modulus increased by 3-fold and 5-fold when comparing ALG/PEI/ADA and ALG/PEI to ALG capsules, respectively. Moreover, PEI-coated capsules showed potential antibacterial properties against both Staphylococcus aureus and Escherichia coli, with an apparent inhibition zone. The cell viability results showed that all capsules were cytocompatible (above 75.5%). Cells could proliferate and form spheroids when encapsulated within the ALG/PEI/ADA capsules. Monitoring the spheroid thickness over 5 days of incubation indicated an increasing trend from 39.50 µm after 1 day to 66.86 µm after 5 days. The proposed encapsulation protocol represents a new in vitro platform for developing 3D cell cultivation and can be adapted to fulfill the requirements of various biomedical applications.

MLATE: Machine learning for predicting cell behavior on cardiac tissue engineering scaffolds.

Cardiovascular disease is one of the leading causes of mortality worldwide and is responsible for millions of deaths annually. One of the most promising approaches to deal with this problem, which has spread recently, is cardiac tissue engineering (CTE). Many researchers have tried developing scaffolds with different materials, cell lines, and fabrication methods to help regenerate heart tissue. Machine learning (ML) is one of the hottest topics in science and technology, revolutionizing many fields and changing our perspective on solving problems. As a result of using ML, some scientific issues have been resolved, including protein-folding, a challenging problem in biology that remained unsolved for 50 years. However, it is not well addressed in tissue engineering. An AI-based software was developed by our group called MLATE (Machine Learning Applications in Tissue Engineering) to tackle tissue engineering challenges, which highly depend on conducting costly and time-consuming experiments. For the first time, to the best of our knowledge, a CTE scaffold dataset was created by collecting specifications from the literature, including different materials, cell lines, and fabrication methods commonly used in CTE scaffold development. These specifications were used as variables in the study. Then, the CTE scaffolds were rated based on cell behaviors such as cell viability, growth, proliferation, and differentiation on the scaffold on a scale of 0-3. These ratings were considered a function of the variables in the gathered dataset. It should be stated that this study was merely based on information available in the literature. Then, twenty-eight ML algorithms were applied to determine the most effective one for predicting cell behavior on CTE scaffolds fabricated by different materials, compositions, and methods. The results indicated the high performance of XGBoost with an accuracy of 87%. Also, by implementing ensemble learning algorithms and using five algorithms with the best performance, an accuracy of 93% with the AdaBoost Classifier and Voting Classifier was achieved. Finally, the open-source software developed in this study was made available for everyone by publishing the best model along with a step-by-step guide to using it online at: https://github.com/saeedrafieyan/MLATE.

Dual-crosslinked in-situ forming alginate/silk fibroin hydrogel with potential for bone tissue engineering.

This study aimed to improve the mechanical and biological properties of alginate-based hydrogels. For this purpose, in-situ forming hydrogels were prepared by dual crosslinking of Alginate (Alg)/Oxidized Alginate (OAlg)/Silk Fibroin (SF) through simultaneous ionic gelation using CaCO3-GDL and Schiff-base reaction. The resulting hydrogels were characterized by FTIR, SEM, compressive modulus, and rheological tests. Compared to the physically-crosslinked alginate hydrogel, the compressive modulus of dual-crosslinked Alg/OAlg/SF hydrogel increased from 28 to 67 kPa, due to the covalent imine bond formation. Then, MTT and DAPI staining assays were performed to demonstrate the biocompatibility of hydrogel. Furthermore, the differentiation potential of bone marrow mesenchymal stem cells encapsulated in hydrogel scaffolds to bone tissue was tested by ALP activity, Alizarin Red staining, and real-time PCR. The overall results showed the potential of Alginate/Oxidized Alginate/Silk Fibroin hydrogel scaffold for bone tissue engineering applications.

Preparation of gum tragacanth/poly (vinyl alcohol)/halloysite hydrogel using electron beam irradiation with potential for bone tissue engineering.

Nanocomposite hydrogels based on tyramine conjugated gum tragacanth, poly (vinyl alcohol) (PVA), and halloysite nanotubes (HNTs) were prepared by electron beam irradiation and characterized. The FTIR, 1H NMR, and TGA results confirmed the chemical incorporation of HNTs into gum tragacanth. Gel content and swelling of hydrogels decreased with HNTs loading up to 20 % wt. The mechanical strength of hydrogels increased by increasing HNTs content up to 10 % with 371 kPa fracture stress at 0.95 fracture strain, compared to 312 kPa stress at 0.79 strain for gum tragacanth/PVA hydrogel. Hydrogel's biocompatibility and osteogenic activity were tested by seeding rabbit bone marrow mesenchymal stem cells. The cell viability was >85 % after 7 days of culture. In vitro secretion of ALP and calcium deposition on hydrogels in alizarin red assay after 21 days of culture indicated hydrogel potential for bone tissue engineering.

Highly efficient porous magnetic polydopamine/copper phosphate with three-dimensional hierarchical nanoflower morphology as a selective platform for recombinant proteins separation.

The separation and purification of recombinant pharmaceutical proteins is a fundamental and challenging step in the biotechnology industry. Hierarchical nanostructures with unique features and high stability can be used as efficient adsorbents. In this study, hierarchical magnetic polydopamine-copper phosphate nanoflowers (Cu-PDA MNFs) were synthesized as high-performance magnetic adsorbents in a simple and low-cost method based on green chemistry. The prepared hybrid Cu-PDA MNFs revealed great performance for separating pure recombinant human growth hormone (rhGH) and the rhGH acquired from recombinant Pichia pastoris yeast fermentation. The analysis confirmed that Cu-PDA MNFs exhibited a high adsorption capacity of 257.4 mg rhGH g-1 Cu-PDA MNFs and a fast adsorption rate for approaching the adsorption equilibrium within less than 30 min with a recovery efficiency of 74% of rhGH from the real sample. In addition, recycling tests demonstrated the stability and recyclability of Cu-PDA MNFs for at least six cycles with almost constant adsorption capacity and no toxicity. Based on these results, Cu-PDA MNFs could be considered as a promising candidate for separation and purification of rhGH. This work presents a new approach to using organic-inorganic nanoflowers as the hierarchical nanostructure for purification of pharmaceutical proteins with high performance.

Drug in adhesive transdermal patch containing antibiotic-loaded solid lipid nanoparticles.

The structure of the skin only allows those hydrophobic elements to penetrate through the depth of the skin with low molecular weight (less than 500 Da) and low daily dose (less than 100 mg/day). Skin penetration of many drugs such as antibiotics at a high daily dose remains an unresolved challenge. In this study a transdermal patch using cephalexin as an antibiotic drug model was developed. Cephalexin was loaded into α-tocopherol succinate-based solid lipid nanoparticles (SLNs). Cephalexin-loaded SLNs with a drug/lipid ratio of 20%, diameter of 180 ± 7 nm, and drug loading 7.9% led to the greatest inhibition zone of Staphylococcus aureus and showed the highest skin permeation capabilities. Cephalexin-loaded SLNs were distributed into poly-iso-butylene adhesive solution and final patches prepared using solvent casting. The physico-chemical characteristics, in vitro drug release, antimicrobial efficacy, and skin cell proliferation properties of patches were evaluated. Results indicated that the optimal transdermal patch formulation containing 90% adhesive solution, 7% cephalexin, and 3% cephalexin-loaded SLNs (with antibiotic content approximately 28% less) inhibited growth of S.aureus better than the formulation containing 90% adhesive solution and 10% cephalexin. In vitro evaluation of the growth of human fibroblast skin cells in media with the optimal patch exhibited greater proliferation (about 25.5%) than those in media without the patch.

Preparation, optimization, and evaluation of midazolam nanosuspension: enhanced bioavailability for buccal administration.

Midazolam is considered as one of the best first-line drugs in managing status epilepticus in children who require emergency drug treatment. Due to poor water solubility, oral bioavailability of midazolam is relatively low. To improve its dissolution and absorption, midazolam nano-suspensions were formulated with different stabilizers using the ultrasonic technique. A combination of Tween 80 and Poloxamer (TP) was considered as one stabilizer and 3-methyl chitosan (TMC) as another stabilizer. The ratio of the stabilizers was selected as an independent variable, and their effects on the particle size and the zeta potential were evaluated by the simplex lattice mixture method. The freeze-dried optimized midazolam nano-suspension powder was characterized by particle-size analysis, SEM, the stability test, and the dissolution test. The optimized midazolam nano-suspension (containing 76% TMC and 24% TP) had a mean particle size of 197 ± 7 nm and a zeta potential of 31 ± 4 (mV). The stability test showed that the midazolam nano-suspension is stable for 12 months. In the in vitro dissolution test, the midazolam nano-suspension showed a marked increase in the drug dissolution percentage versus coarse midazolam. In the in vivo evaluation, the midazolam nano-suspension exhibited a significant increase in the Cmax and the AUC0-5, and a major decrease in Tmax. The overall results indicate the nano-suspension of midazolam is a promising candidate for managing status epilepticus in children in emergency situation.

Injectable chitosan hydrogel embedding modified halloysite nanotubes for bone tissue engineering.

Low mechanical strength and untargeted osteoinduction of chitosan hydrogel limit its application for bone regeneration. This study aimed to develop an injectable chitosan hydrogel with enhanced mechanical strength and improved osteoinductivity for bone tissue engineering. For this purpose, chitosan-modified halloysite nanotubes (mHNTs) were synthesized first. Then, icariin as a bone inducer was loaded into mHNTs (IC@mHNTs), resulting in a sustained drug release system. Further, nanocomposite chitosan/mHNTs hydrogels were prepared by the sol-gel transition, leading to decreased gelation time and temperature and enhanced mechanical strength of the resulting scaffolds. The mesenchymal stem cells were encapsulated into the hydrogels, and in vitro viability assays showed scaffold biocompatibility. Moreover, embedded mHNTs or IC@mHNTs in the scaffold resulted in enhanced proliferation and bone differentiation of encapsulated cells. It was collectively demonstrated that the injectable in situ forming nanocomposite chitosan hydrogel loaded with IC@mHNTs is a promising candidate for bone regeneration.

Effect of molecular mass of methoxypoly(ethylene glycol) activated with succinimidyl carbonate on camouflaging pancreatic islets.

The surface modification of Langerhans islets by grafting activated poly(ethylene glycol) on to their capsules in order to prevent immune-system stimulation is a novel method in diabetes cell therapy. In the present study, mPEG [methoxypoly(ethylene glycol)] with two molecular masses of 5 and 10 kDa, activated with SC (succinimidyl carbonate), was grafted on to the surface of pancreatic islets at a polymer concentration of 22 mg/ml. It was found that PEGylated islets were viable and active, and no morphological changes on the collagen capsule of islets were observed. The amount of interleukin-2 secretion from lymphocytes co-cultured with islets PEGylated with mPEG-SC of 5 and 10 kDa was 112.12 ± 23.09 pg/ml and 172.75 ± 27.94 pg/ml respectively. Thus mPEG-SC (SC-activated mPEG) with higher molecular mass was more suitable for camouflaging islets from the immune system.

Preparation and characterization of ketoprofen-loaded solid lipid nanoparticles made from beeswax and carnauba wax.

Solid lipid nanoparticles (SLNs) have been proposed as suitable colloidal carriers for delivery of drugs with limited solubility. Ketoprofen as a model drug was incorporated into SLNs prepared from a mixture of beeswax and carnauba wax using Tween 80 and egg lecithin as emulsifiers. The characteristics of the SLNs with various lipid and surfactant composition were investigated. The mean particle size of drug-loaded SLNs decreased upon mixing with Tween 80 and egg lecithin as well as upon increasing total surfactant concentration. SLNs of 75 ± 4 nm with a polydispersity index of 0.2 ± 0.02 were obtained using 1% (vol/vol) mixed surfactant at a ratio of 60:40 Tween 80 to egg lecithin. The zeta potential of these SLNs varied in the range of -15 to -17 (mV), suggesting the presence of similar interface properties. High drug entrapment efficiency of 97% revealed the ability of SLNs to incorporate a poorly water-soluble drug such as ketoprofen. Differential scanning calorimetry thermograms and high-performance liquid chromatographic analysis indicated the stability of nanoparticles with negligible drug leakage after 45 days of storage. It was also found that nanoparticles with more beeswax content in their core exhibited faster drug release as compared with those containing more carnauba wax in their structure.

The effect of two different polyethylene glycol (PEG) derivatives on the immunological response of PEG grafted pancreatic islets.

Islet transplantation is one of the promising ways to treat diabetes. To reduce the immune system response, several methods have been developed, a novel one being the grafting of methoxy polyethylene glycol (mPEG) derivatives onto collagen capsules of islets. In this study, the effects of the first and second generations of activated mPEG on the immunological response of polyethylene glycol (PEG) grafted pancreatic islets were studied. mPEG-Succinimidyl carbonate (mPEG-SC) and mPEG-succinimidyl propionic acid (mPEG-SPA) (with nominal molecular weight 5 kDa), typical of the first and second generations of activated mPEG, were selected, respectively. Both activated mPEGs did not affect the morphology, viability, or functionality of PEGylated islets compared to free islets (naked islets). The amount of IL-2 secreted from lymphocytes co-cultured with mPEG-SPA grafted islets (131.83 ± 15.28 pg/ml) was not significantly different from that with mPEG-SC grafted islets (156.09 ± 27.94 pg/ml). These results indicated that both mPEG-SC and mPEG-SPA had the same effect for camouflaging Langerhans islets, but the former is more suitable due to its easier synthesis process.

Effect of polymer concentration on camouflaging of pancreatic islets with mPEG-succinimidyl carbonate.

Modifying the surface of living cells with specially selected polymers is a new method of protecting them from the immune system. Covalent attachment of polyethylene glycol (PEG) derivatives on the capsule of pancreatic islets in aqueous media under moderate conditions is an example. This study aimed to find out whether higher polymer concentration could protect PEGylated islets from immune systems more efficiently without affecting their viability and morphology. Methoxy polyethylene glycol succinimidyl carbonate (mPEG-SC) with molecular weight of 5 kDa at different concentrations was grafted onto islets capsules. It was found that at polymer concentrations higher than 22 mg/mL, islets lost their viability with changes in their surface structure as compared to free islets. At mPEG-SC concentrations less than 22 mg/mL, there was no change in morphology and viability of PEGylated islets, but PEGylation of islets at polymer concentration 7 mg/mL was not sufficient for their camouflaging. Polymer concentration of 22 mg/mL was more effective in weakening the immunogenicity of islets. It was concluded that increasing the 5kDa mPEG-SC concentration up to 22 mg/ml protected islets from the immune cells more efficiently without affecting their viability and functionality.

Optimization of PEGylation conditions for BSA nanoparticles using response surface methodology.

Chemical coupling of polyethylene glycol (PEG) to proteins or particles (PEGylation), prolongs their circulation half-life by greater than 50-fold, reduces their immunogenicity, and also promotes their accumulation in tumors due to enhanced permeability and retention effect. Herein, phase separation method was used to prepare bovine serum albumin (BSA) nanoparticles. PEGylation of BSA nanoparticles was performed by SPA activated mPEG through their free amino groups. Effect of process variables on PEGylation efficiency of BSA nanoparticles was investigated and optimized through response surface methodology with the amount of free amino groups as response. Optimum conditions was found to be 32.5 g/l of PEG concentration, PEG-nanoparticle incubation time of 10 min, incubation temperature of 27°C, and pH of 7 for 5 mg of BSA nanoparticles in 1 mL phosphate buffer. Analysis of data showed that PEG concentration had the most noticeable effect on the amount of PEGylated amino groups, but pH had the least. Mean diameter and zeta potential of PEGylated nanoparticles under these conditions were 217 nm and -14 mV, respectively. In conclusion, PEGylated nanoparticles demonstrated reduction of the negative surface charge compared to the non modified particles with the zeta potential of -31.7 mV. Drug release from PEGylated nanoparticles was almost slower than non-PEGylated ones, probably due to existence of a PEG layer around PEGylated particles which makes an extra resistance in opposition to drug diffusion.

Dual responsive chondroitin sulfate based nanogel for antimicrobial peptide delivery.

Poly (l-lactide)-graft-chondroitin sulfate (PLLA-g-CS) copolymers were synthesized with different l-lactide contents via ring-opening polymerization. Chemical structure of the synthesized copolymers was confirmed by FTIR and HNMR analyses. The degree of polymerization and substitution of PLLA was found to be 0.56 and 2.98, respectively. Nisin was loaded in PLLA-g-CS nanogels at 37 and 42 °C. The hydrodynamic radius of the nanogels was 181 and 399 nm, respectively. The release profile was studied at two different temperatures and pHs over 7 days. The results indicated a variation of the cumulative release of nisin from 25 to 98% depending on the pH and temperature of release media. Cytotoxicity test of nisin loaded nanogels on human dermis fibroblast cells, confirmed no toxic effect. Finally, Antimicrobial activity of the nanogel was evaluated against Staphylococcus aureus and Escherichia coli bacteria. Overall, this study indicated that the dual responsive nanocarrier could potentially be used for infection therapeutic applications.