228 results about "Tissue engineering" patented technology

The invention relates to the technical field of biology, and particularly discloses a recombinant collagen III and application thereof in preparation of gel. The recombinant collagen III is designed by optimizing functional area sequences of human I-type and III-type collagen, the amino acid sequence is shown as SEQ ID No.2, and the recombinant collagen III has the characteristics of high stability, good hydrophilicity and low immunogenicity. The preparation method comprises the steps of expression vector construction, escherichia coli induced expression, affinity chromatography purification and renaturation. The recombinant collagen III can be prepared into a gel dressing and comprises sodium alginate, methylparaben and other components. Experiments show that the gel can effectively promote cell proliferation and has no cytotoxicity; in a mouse skin injury model, the collagen can relieve inflammation, accelerate wound healing and inhibit scar formation, and the effect of the collagen is superior to that of natural human III-type collagen. The invention provides a safe and efficient novel material for wound repair, and is suitable for medical dressings and tissue engineering.

The invention relates to the technical field of synthetic biology, in particular to recombinant XVII type collagen as well as a preparation method and application thereof.The amino acid sequence of the recombinant XVII type collagen comprises a sequence shown in any one of SEQ ID NO.1-SEQ ID NO.3. The recombinant XVII type collagen can be highly expressed in an escherichia coli and pichia pastoris system, the expression system is simple, the cost is low, and the recombinant XVII type collagen is suitable for industrial production. The yield is high; the biological activity is good. The protein can be compounded with other proteins to form raw materials of tissue engineering products, cosmetics, health care products or medicines, so that the protein can be widely applied to the fields of medicines, medical instruments, biological materials, tissue engineering, cosmetics and the like.

The invention belongs to the technical field of biomedical tissue engineering materials, and particularly relates to injectable composite plastic gel and a preparation method thereof. The injectable plastic gel provided by the invention is formed by suspending and compounding the cross-linked sodium hyaluronate gel particles and the biological tissue extracellular matrix particles, the two material particles in the injectable composite plastic gel are uniform in size and controllable in size, other toxic catalysts do not need to be added in the preparation process, and the injectable plastic gel is easy to prepare. The collagen / elastin composite material is rich in collagen and elastin, and shows good biomechanical properties. Meanwhile, the composite plastic gel contains a plurality of bioactive factors, and after the composite plastic gel is injected and filled into a body, the composite plastic gel is slowly degraded and can promote the generation and ingrowth of autologous fat cells and microvessels, so that the balance of degradation and remodeling is achieved. The preparation method of the injectable plastic gel provided by the invention can be widely applied to the fields of plastic surgery, medical beauty and the like.

The invention discloses starch-collagen composite hydrogel as well as a preparation method and application thereof. Collagen is catalyzed by microbial transglutaminase to form a covalent cross-linked network, and meanwhile, hydroxypropyl starch is introduced to construct a physical interpenetrating network through molecular chain penetration and hydrogen-bond interaction; and chondroitin sulfate is further integrated to strengthen the network structure and biological activity through electrostatic interaction. The method is mild in condition and does not need a toxic chemical cross-linking agent, the obtained composite hydrogel has an interpenetrating double-network structure and has excellent mechanical properties, enzymatic degradation resistance and cell affinity, the compression modulus of the composite hydrogel is remarkably improved, the composite hydrogel can keep structural stability for a long time in a collagenase environment, cell adhesion and proliferation can be effectively promoted, and the composite hydrogel has a good application prospect. The hydrogel can be widely applied to tissue engineering scaffolds, wound dressings, drug sustained-release carriers and cartilage repair materials.

The invention discloses composite hydrogel bio-ink with a function of space-time delivery of double growth factors as well as a preparation method and application of the composite hydrogel bio-ink, and belongs to the technical field of biomedical materials and tissue engineering. According to the preparation method, imidazolyl-modified methacrylated gelatin and double-bonded PF127 are compounded, and meanwhile, free vascular endothelial growth factors and connective tissue growth factor-loaded PLGA microspheres are entrapped in a system, so that the bio-ink with excellent printability, high adhesion, swelling resistance and space-time delivery function is formed; the bio-ink physically has the advantages of high printing fidelity, low swelling property, high mechanical strength and strong tissue adhesion of a synthetic material; in biology, the system can be used as an intelligent carrier to realize programmed space-time delivery of various growth factors, so that complex cell biological behaviors are accurately arranged, and real regeneration of functional tissues is guided.

The invention belongs to the technical field of hydrogel preparation, and discloses a biocompatible self-healing photocuring hydrogel and a preparation method and a use method thereof.The biocompatible self-healing photocuring hydrogel is prepared by adding an ultraviolet light initiator and sodium chloride into a polyvinyl alcohol aqueous solution, evenly mixing, then adding acryloyl glycinamide powder to enable the acryloyl glycinamide powder to be dissolved, then adding a crosslinking agent, and evenly mixing to obtain the biocompatible self-healing photocuring hydrogel. Adding water into the mixed solution, then removing bubbles, then adding methacrylated gelatin and dissolving, and then removing bubbles to obtain a biocompatible self-healing photocuring hydrogel mixed solution; adding a borax solution prepared from sodium tetraborate and deionized water into the obtained biocompatible self-healing light-cured hydrogel mixed solution, and after the biocompatible self-healing light-cured hydrogel mixed solution and the borax solution are subjected to cross-linking reaction, removing bubbles to obtain the biocompatible self-healing light-cured hydrogel. The biocompatible self-healing photocuring hydrogel has excellent mechanical properties and self-healing ability, and is suitable for application scenes such as biosensing, wound repair and tissue engineering.

The invention belongs to the technical direction of protein engineering in the technical field of biology, and particularly relates to a triple-helix folding and stabilizing method for recombinant collagen, which is a technology for efficiently assisting correct folding of human recombinant collagen expressed by escherichia coli and forming a stable triple-helix structure. The technology mainly solves the common key technical problems of low folding efficiency, unstable triple helix structure and the like of the recombinant collagen in an escherichia coli expression system, and obviously improves the yield of the functional recombinant collagen. The method has important application value in the fields of biomedical materials, tissue engineering, beauty and skin care and the like, and an efficient and economical technical path is provided for industrial production of recombinant collagen.

The invention discloses a water-soluble silk fibroin with a random crimp / Silk I structure as a main structure as well as a preparation method and application of the water-soluble silk fibroin. The silk fibroin product is characterized in that in a protein secondary structure, the total content of random curls and Silk I structures exceeds 85%, and the proportion of Silk I in the whole crystal structure is not lower than 75%; the product can be directly dissolved in water at room temperature to form a stable clarified solution with the concentration not lower than 5%, and is not gelatinized after being stored at 4 DEG C for 90 days. The preparation method comprises the following steps: degumming and cleaning the mulberry silk raw material; the method comprises the following steps: carrying out short-time (less than or equal to 20 minutes) high-temperature dissolution by adopting a multi-element solution dissolution system with a specific ratio, and then carrying out dialysis purification at a low temperature by taking the conductivity (lt, 10 [mu] S / cm) of a dialysis external liquid and the concentration (lt, 50 ppm) of calcium ions as double end-point standards. The directional regulation and control of the silk fibroin structure are realized through the accurate control of the whole process, and the obtained product has excellent water solubility, storage stability and biological safety, and can be widely applied to the fields of drug delivery, 3D biological printing, medical beauty filling, tissue engineering and the like.

The invention discloses a multi-scale artificial dermal scaffold and a preparation method thereof, and belongs to the technical field of tissue engineering and biomedical materials. The artificial dermal scaffold is of a three-dimensional porous structure formed by microfilaments of a first frame and a second frame, the microfilaments of the second frame are distributed in pores of the first frame, disordered microfilaments which do not affect the penetrability of the macropores are arranged in the macropores in the top surface of the first frame, and longitudinally aligned microfilaments are arranged in the micropores in the section of the first frame. Through the specific structure, the adhesion, proliferation and migration effects of cells can be remarkably improved, and rapid vascularization of artificial dermis is facilitated. In addition, the preparation process of the artificial dermal scaffold is simple and easy to operate, can be used for batch preparation, and has a good application prospect.

This invention belongs to the interdisciplinary field of biomedical engineering, materials science, and tissue engineering, and discloses a multifunctional hydrogel with switchable mechanical and adhesive properties based on temperature triggering, its preparation method, and applications. The invention consists of acrylic acid, gelatin, hexadecyltrimethylammonium bromide, polydopamine nanoparticles loaded with silver nanoparticles, and water. This invention not only exhibits excellent adhesion and mechanical properties to skin tissue but also possesses switchable mechanical and adhesive properties, achieving durable and repeatable adhesion. The temperature-triggered hydrogel prepared by this invention is simple to process, low in cost, and introduces no toxic chemicals. It can achieve a close fit at body temperature and natural detachment at low temperatures, driven by temperature, and maintains excellent adhesion properties even in complex environments, thus promoting the development of intelligent medical multifunctional wound dressings.

The invention belongs to the technical field of bioengineering, and relates to heparan sulfate defect type matrigel as well as a preparation method and application thereof. The preparation method comprises the following steps: providing natural matrigel; providing immobilized heparinase, wherein the immobilized heparinase can specifically catalyze and degrade heparan sulfate in the natural matrigel; carrying out contact reaction on the natural matrigel and the immobilized heparinase; and after the reaction is finished, separating the immobilized heparinase. According to the preparation method, the characteristics that the immobilized enzyme is convenient to separate and recycle are utilized, the problems that in a traditional solution enzyme method, enzyme residues exist, the reaction is difficult to accurately control, and subsequent purification steps are complex are solved, and a standardized heparan sulfate defective matrigel product which is controllable in component, free of residual enzyme and high in stability is provided. The method has wide application value in the fields of tumor mechanism research, anti-tumor drug screening, tissue engineering and the like.

The invention discloses a metal ion induced alginate aerogel fiber as well as preparation and application thereof. The method comprises the following steps: pre-mixing a sodium alginate solution with a coagulating bath solvent to obtain a uniform spinning solution; extruding the spinning solution into an alcohol coagulating bath through wet spinning to form sodium alginate primary gel fibers; then, introducing the nascent fiber into a calcium ion cross-linking solution with a specific concentration for cross-linking and curing; and finally, drying at normal temperature and normal pressure to obtain the calcium alginate aerogel fiber. The method is simple in process and low in cost, and the obtained fiber has wide application prospects in the fields of adsorption separation, heat insulation, tissue engineering and the like.

The application discloses a kind of small molecule compound combination and the method for preparing vascular endothelial cell using the small molecule compound combination induced differentiation cell.The method is directed to induce differentiated cell, and finally prepare vascular endothelial cell;The directional induction includes inhibiting the activity of lysine deacetylase, inhibiting the signal path of TGF-β, inhibiting the activity of DNA methyltransferase (DNMT), activating the signal path of WNT / β-catenin and activating the signal path of cAMP.The present application can be converted into vascular endothelial cell by small molecule compound combination induction, and each step can realize accurate quality control, which is convenient for standardized operation and large-scale production.The method provided by the present application has wide donor sources, and the patient himself can be used as a donor, so that the vascular endothelial cells required for basic research, clinical treatment or tissue engineering production can be obtained in a short time.

The invention discloses a potato protein with good emulsibility, gelling property and foamability, and belongs to the fields of biology and genetic engineering. According to the invention, the designed potato protein realizes recombinant expression in pichia pastoris, and it is verified that the recombinant expressed protein can form a secondary structure and can form hydrogel at a concentration of 60 g / L. The invention also provides an application of the prepared potato protein as a food additive, shows emulsifying and gelling capabilities superior to those of commercial potato protein, and has huge value and potential in the fields of food and tissue engineering.

This invention discloses a multi-enzyme preparation for industrial cell dissociation, its usage method, and applications, belonging to the field of seed cell extraction technology for industrial meat culture. The invention employs a multi-enzyme preparation composed of component 1 and component 2; component 1 includes neutral protease, hyaluronidase, and elastase; component 2 includes matrix metalloproteinase, papain, and plasmin. The invention also discloses the preparation method and applications of the multi-enzyme preparation. The rational enzyme ratio and optimized treatment conditions of this invention help protect cell membrane integrity, maintain high cell activity, and significantly improve dissociation efficiency and cell recovery. The compound enzyme preparation is highly adaptable, applicable to various tissue types and dissociation requirements, and facilitates standardized and large-scale production. Combined with automated dissociation equipment, the compound enzyme preparation enables efficient and stable industrial operation, providing important technical support and broad application prospects for the cultured meat industry, tissue engineering, and cell therapy.

The application discloses a preparation method of a semi-interpenetrating network hydrogel based on an amino-succinimide ring-opening reaction, which comprises the following steps: firstly, a hydrophilic compound containing amino groups, such as trishydroxymethylaminomethane, is used to modify polysuccinimide to obtain water-soluble polysuccinimide polymer; N-vinylcaprolactam and 3-mercaptopropionic acid are reacted to obtain poly-N-vinylcaprolactam polymer with terminal carboxyl groups; and the polymer is used to graft hydroxypropyl methyl cellulose to obtain macromolecular hydroxypropyl methyl cellulose derivative. The water-soluble polysuccinimide, the polymer containing amino groups and the hydroxypropyl methyl cellulose derivative are dissolved in water, and the amino-succinimide ring-opening reaction is utilized to obtain the hydrogel; the hydrogel is soaked in water to remove uncrosslinked components; and after drying, the semi-interpenetrating network hydrogel is obtained. The preparation process is simple, the conditions are mild, and the reaction speed is fast; and the prepared hydrogel has pH / temperature sensitivity and can be used in many fields such as tissue engineering, drug release, water treatment and the like.

This invention discloses a method for culturing skin organoids for large-scale production and the skin organoids used for large-scale production, belonging to the fields of tissue engineering and biomanufacturing technology. The method involves laying a dermal matrix layer composed of orthogonal double-network hydrogels embedding fibroblasts in a bioreactor containing multiple independently operable culture modules. After inoculating keratinocytes, negative pressure is used to drive a uniform descent of the culture medium level to achieve gas-liquid interface culture. The first network of the orthogonal double-network hydrogel is formed by photocrosslinking of methacrylamide recombinant collagen, and the second network is formed by Michael addition of thiolated polysaccharides and multi-arm polyethylene glycol maleimide. During the culture process, the barrier maturity is assessed in real time by online monitoring of transepithelial resistance, and the negative pressure is controlled accordingly. A single batch can produce 3000 cm³ of skin organoids. 2 The above-mentioned qualified skin organoids have a transepithelial resistance coefficient of variation of less than 10%.

The invention belongs to the technical field of 3D printing biology, and particularly relates to bio-ink based on a solvent-free citric acid base, a preparation method of the bio-ink, a 3D printing method and application of the bio-ink. Comprising the following steps: performing polycondensation, ester exchange or substitution reaction on citric acid and a compound containing carboxyl, hydroxyl, amino or anhydride group to prepare a citric acid-based prepolymer; and the citric acid-based prepolymer and a thickening agent are compounded to prepare the citric acid-based bio-ink suitable for extrusion type 3D printing. According to the citric acid-based bio-ink based on extrusion type 3D printing, an efficient and accurate method is provided for expanding the application of citric acid-based biological materials in tissue engineering; the rheological curing characteristics of the citric acid-based bio-ink are optimized by regulating and controlling the reaction conditions of the citric acid-based prepolymer and the compounding proportion of the thickening agent.

The invention discloses a bionic heterogeneous tissue engineering meniscus stent and a preparation method thereof, and discloses application of the bionic heterogeneous tissue engineering meniscus stent in the field of meniscus repair. Based on a multi-nozzle 3D printing technology, a biodegradable high polymer material and bio-ink loaded with growth factors / stem cells are innovatively adopted, and the highly bionic heterogeneous tissue engineering meniscus is constructed. Specifically, degradable macromolecular polycaprolactone (PCL) is used as a raw material, and annular and radial fibers are printed to form a stent frame by accurately regulating and controlling a printing path and simulating a natural meniscus collagenous fiber distribution rule; on the basis, biological ink loaded with differentiated growth factors and stem cells is printed in a staggered manner according to different physiological characteristics of a red region and a white region of the meniscus, so that partitioned precise inoculation of seed cells and controllable partitioned release of the growth factors are realized, and a cell microenvironment with spatial specificity is provided for meniscus regeneration; the tissue repair efficiency and the bionic integrating degree are obviously improved.

The invention relates to the technical field of tissue engineering, and particularly discloses a lamina-free three-dimensional aneurysm chip as well as a preparation method and application thereof. The method comprises the following steps: firstly, designing a non-layered three-dimensional aneurysm chip mold which comprises a semi-aneurysm part capable of being accurately matched with aneurysm physiological structural characteristics, then preparing a non-layered three-dimensional aneurysm chip mold blank by adopting a photocuring 3D printing technology, and then coating a photosensitive resin mixture to obtain the non-layered three-dimensional aneurysm chip mold. Laminated lines on the surface layer of the mold blank are eliminated through the steps of spin coating treatment, ultraviolet curing and the like, the roughness of the surface of the mold blank is optimized, and finally the three-dimensional aneurysm chip is prepared through the soft photoetching technology. According to the method, through a series of combined processes of mold design, mold blank 3D printing, mold blank layer grain elimination and soft photoetching of the chip, the recarving precision of the three-dimensional aneurysm chip is remarkably improved, and the strict requirement of an aneurysm in-vitro simulation experiment for the structural precision is met; the technical defects that an existing three-dimensional aneurysm chip is low in precision, obvious in lamina and the like are overcome.

The application discloses a kind of zwitterionic composite hydrogel adhesive and preparation method thereof, the method uses one-pot copolymerization method, with MBAA and borax as crosslinking agent, preparation contains SBMA, PVA, THMA and AMPS zwitterionic polyelectrolyte hydrogel, with excellent adhesive property and biocompatibility, suitable for biological medicine field.The method polyvinyl alcohol enhances the physical properties of hydrogel due to its crosslinking site and hydrogen bond.SBMA cationic and anionic group improves the adhesive property, and the reaction monomer THMA provides hydrogen bond effect, further promotes adhesion, so that the prepared hydrogel adhesive exhibits excellent adhesive property and biocompatibility, suitable for wound dressing, drug release system and tissue engineering biological medicine applications.

The invention discloses a method for preparing a wet spinning alignment collagen membrane with high tensile strength, and relates to the technical field of biomedical material preparation, the method comprises the following steps: preparing three layers of solutions, the upper layer and the lower layer are wet spinning buffer solutions (such as a polyethylene glycol solution) with specific concentration and pH, and the middle layer is a collagen solution with specific concentration and pH; injecting the three-layer solution into three-layer flow control equipment, and controlling the flow through a collecting tube; gathering the three layers of solutions at the tail end of equipment and performing wet spinning to form a film; and axially stretching to obtain a finished product. According to the invention, by precisely regulating and controlling a solution system, adopting industrial-grade flow control equipment and flow control, optimizing a directional stretching process and stabilizing a curing environment, the problems of non-uniform film thickness, easy tearing, large mechanical property fluctuation and the like in a traditional process are solved, large-scale production of the collagen film with high tensile strength and directionally arranged molecules is realized, and the production cost is reduced. The method is suitable for artificial blood vessels, bile ducts, skin and other tissue engineering fields.

This invention provides a rigid silk fibroin material with controllable mechanical properties, its preparation method, and its applications, belonging to the field of medical material preparation. The preparation method includes the following steps: a silk fibroin solution is subjected to low-temperature freezing and annealing to form a Silk I-type insoluble substance; after drying, it is pulverized and granulated to obtain regenerated silk fibroin powders of different particle sizes; subsequently, hot pressing is performed to obtain rigid silk fibroin materials with different mechanical properties. This invention uses hot pressing of Silk I-structured silk fibroin to replace the traditional hot pressing process of amorphous silk fibroin, avoiding the high energy consumption and time-consuming freeze-drying process; furthermore, this invention controls the particle size of the regenerated silk fibroin powder through granulation, achieving regulation of the mechanical properties of the rigid silk fibroin material to adapt to the mechanical properties required for repair materials in different application scenarios, and can be applied in orthopedics, tissue engineering, and other fields.

The application discloses a preparation method and application of a nerve conduit with a multistage biomimetic nerve membrane structure and belongs to the technical field of tissue engineering materials. The nerve conduit with the multistage biomimetic nerve membrane structure comprises a biomimetic inner membrane support with a secondary guiding structure and a biomimetic outer membrane support with a double-layer structure. In the nerve conduit with the multistage biomimetic nerve membrane structure, the filler for playing a growth guiding role has a multistage guiding structure, the primary guiding is that cells are directionally migrated along the fiber direction in the directional fiber membrane, are elongated in shape on the fiber and are accelerated in differentiation, and the secondary guiding is that directional microchannels constrain the growth of nerve fibers, promote the maturation of bundling and the alignment of the growth direction. The application solves the problem of insufficient contact guiding efficiency existing in the prior art and overcomes the contradiction between the filling density of guiding fibers, the growth space and the guiding effect.

The invention belongs to the technical field of biomedical materials and tissue engineering, and particularly relates to hydrogel for treating ulcerative colitis and a preparation method thereof. The hydrogel is prepared from four functional components including oxidized dextran, chitosan, L-arginine and trithiohydracrylic acid through synergistic crosslinking, wherein the four functional components include the oxidized dextran, the chitosan, the L-arginine and the trithiohydracrylic acid; an aldehyde group of the oxidized dextran and an amino group of the chitosan are subjected to a Schiff base reaction to form a dynamic covalent cross-linked network, and a basic skeleton of the hydrogel is formed; l-arginine and guanidyl are integrated into the dynamic covalent cross-linked network through amino of the L-arginine, and trimercaptopropionic acid and carboxyl of the trimercaptopropionic acid are integrated into the dynamic covalent cross-linked network through a covalent bond or a non-covalent effect through sulfydryl of the trimercaptopropionic acid, so that a multi-site synergistic cross-linked structure is formed. The invention can solve the technical problems of single function, weak targeting property, insufficient oxidation resistance, short mucous membrane residence time, side effect risk caused by loading of exogenous drugs, limited curative effect, drug resistance and the like of the traditional treatment material.

The invention provides a developing agent which is modified iopamidol, a clinically safe nonionic hydrophilic developing agent iopamidol is subjected to structural modification, a hydrophilic side chain and a connecting arm are introduced, and the iopamidol is introduced into a gelatin degradable microsphere matrix with good biocompatibility in a covalent bonding manner; the degradable non-ionic X-ray developing microsphere with good biocompatibility is formed. Developing microspheres prepared by adopting the developing agent provided by the invention not only keep excellent X-ray developing performance, solve the problems of aggregation tendency and biocompatibility of traditional developing microspheres and realize real-time visual monitoring of an embolism process, but also have degradability and good biological safety, and are not only suitable for permanent embolism treatment, but also suitable for treatment of embolism. The solid developing embolism agent can also be expanded to the fields of temporary embolism, tissue engineering and the like, and the solid developing embolism agent with precise developing and safe degradation performance is provided for minimally invasive interventional therapy of diseases such as tumor intervention and vascular malformation.

The application discloses a preparation method of a layer-by-layer self-assembly tissue engineering membrane and application thereof, and belongs to the technical field of medical preparations. The glass slide is taken out after being placed in the SA / glycerin / gelatin solution; the glass slide is taken out after being immersed in the CS / NaCl / glycerin / gelatin solution; the glass slide is immersed in a CaCl2 solution, taken out, dried, and then immersed in ethanol; and the membrane taken off from the glass slide is dried and stored. The application uses chitosan and sodium alginate as main raw materials, and prepares a deformable tissue engineering membrane through a self-assembly and ion replacement method. 2+ and Na + alternating treatment to realize control deformation. The membrane in a diastolic state is used to culture cells until the cells on the membrane surface form a dense monolayer of cells, and then the monolayer of cells is separated from the lower self-assembly membrane through CaCl2 solution treatment, so that the monolayer of cells on the membrane is separated from the lower self-assembly membrane. Thus, a monolayer of cells for tissue engineering is obtained.

The present disclosure relates to a protein-based article comprising a film having a thickness of about 0.1 μm to about 10 mm and comprising a crosslinked network of partially ordered polypeptides, wherein each partially ordered polypeptide independently comprises a plurality of disordered domains and a plurality of ordered domains, wherein each disordered domain independently comprises a PG or GP motif and each ordered domain independently comprises a polyalanine motif or a polyproline motif.

The invention relates to the field of biological materials, in particular to a preparation method of needle-shaped silicon dioxide coated with protein on the surface, which comprises the following steps: S1, treating artificially synthesized needle-shaped silicon dioxide by using a sodium hydroxide aqueous solution; then modifying the amount of the needle-shaped silicon dioxide by using a 3-aminopropyl methyl diethoxy silane modifier; s2, preparing a protein solution; s3, coating the surface of the needle-shaped silicon dioxide with protein by using EDC and NHS; and S4, centrifuging, washing and drying. The method has the beneficial effects that the operation is simple and convenient, the reaction condition is mild (protein denaturation is avoided), the biocompatibility is excellent (non-toxic crosslinking agent residues are left), and the method is suitable for industrial production of biomedical carriers, cosmetic active ingredient loading and tissue engineering materials.

Aspects of the application relate to compositions, systems, apparatuses, and methods for producing a nucleic acid comprising a target sequence, such as a sequence of interest. Producing a nucleic acid can comprise a plurality of ligation and cleavage steps (e.g., a plurality of cycles, each cycle comprising a ligation step and a cleavage step) that result in exponential elongation of a nucleic acid, ultimately generating a nucleic acid of a desired, target sequence. One or more additional steps and / or conditions can be utilized to select for nucleic acids that were successfully ligated, such as the double selection methods described herein. Compositions and methods described herein can be utilized to generate nucleic acids ranging in length from tens or hundreds of nucleotides to hundreds of millions of nucleotides or longer, including nucleic acids having lower error rates that can be achieved with convention nucleic acid synthesis methods alone.