CN111330066A

CN111330066A - Three-dimensional structured biological dressing for repairing skin lesion of severe patient

Info

Publication number: CN111330066A
Application number: CN202010365367.9A
Authority: CN
Inventors: 贾蕊; 王静; 党永辉; 屈彦; 王亮
Original assignee: First Affiliated Hospital of Medical College of Xian Jiaotong University
Current assignee: First Affiliated Hospital of Medical College of Xian Jiaotong University
Priority date: 2020-04-30
Filing date: 2020-04-30
Publication date: 2020-06-26
Anticipated expiration: 2040-04-30
Also published as: CN111330066B

Abstract

The utility model provides a towards prosthetic three-dimensional structure biological dressing of severe patient's skin lesion, comprises back sheet, functional layer, tectorial membrane layer, and the functional layer has the different functional cell layer of three-layer respectively along biological dressing thickness direction: a base layer, an intermediate layer and a surface layer; the base layer close to the film coating layer adopts a cell layer which can be fused with cells of the dermis layer of the skin; the middle layer adopts a multicellular system and growth factors which can promote the growth of the dermis; the surface layer close to the back lining layer adopts a multicellular system capable of promoting the growth of the epidermal layer; the base layer is weakly adhered to the film coating layer; the surface layer is strongly adhered to the back lining layer; the inside of the functional layer is a three-dimensional network structure formed by support beams, and the support beams are in gradient distribution in the thickness direction of the biological dressing, namely the distribution density of the support beams is gradually reduced along with the thickness change from the bottom to the surface; the invention can release bioactive factors to promote the repair of skin lesions, has a gradient three-dimensional network structure and ensures the good contact between the skin lesion position and the dressing when a patient moves.

Description

Three-dimensional structured biological dressing for repairing skin lesion of severe patient

Technical Field

The invention belongs to the technical field of biological materials, and particularly relates to a three-dimensional structured biological dressing for repairing skin lesions of severe patients.

Background

In clinic, severe patients often move inconveniently or lie in bed, large-area skin damage (namely skin damage) is caused due to difficulty in eating, poor nutrition, difficulty in turning over and the like, the incidence rate of skin damage of severe patients in medical institutions reaches 13.1-45.5%, and the incidence rate of communities, nursing institutions and families is higher. The skin of the whole body of a patient is easy to be damaged, and skin damage such as bedsore, fester and the like often occurs at the skin stressed position; incontinence dermatitis caused by disturbance of consciousness and antibiotic-associated diarrhea in some severe patients; severe neurologic disease patients often have pressure skin lesions at the tracheotomy position, the noninvasive ventilator mask position and other stress parts. For severe patients, skin damage not only damages the integrity of the skin, but also provides a channel for the invasion of pathogenic bacteria, thereby greatly increasing the infection probability; on the other hand, skin damage of severe patients increases the burden of nursing staff, prolongs the hospitalization days, increases the medical cost, and is more likely to cause doctor-patient disputes. Therefore, how to meet the requirement of rapid repair of skin lesions of severe patients is of great significance in clinical work.

Aiming at repairing skin lesions, the wet healing of skin lesion wound surfaces is advocated at present, and the skin lesion wound surface healing promoting agent has the advantages of reducing infection, protecting the wound surfaces and accelerating healing. The novel dressing taking hydrogel as a matrix has the characteristics of relieving local skin pressure, providing a wet healing environment, protecting a skin injury wound surface and the like, and has an obvious skin injury repairing effect compared with the traditional modes of only depending on skin cleaning, stress relieving and the like; however, the wet healing mode still depends on the skin repair of the patient, the self-repair of the skin wound is not induced, the process is long, and the requirements of the serious bedridden patient are difficult to meet. The scholars also adopt the combination of human umbilical cord blood stem cells or skin fibroblasts with hyaluronic acid gel and other modes to prepare a single-layer or few-layer film, and utilize the factors which secrete more anti-inflammatory factors and promote growth in stem cell differentiation to improve the rate of healing of skin lesions, thereby obtaining certain results in the experiment of accelerating healing of the skin lesions; however, the method only stays in the mechanism research at present, the prepared film structure is difficult to combine with the real skin with a three-dimensional network structure, dressing falling and failure are easy to generate due to stress change of a skin damage position in the process of nursing a patient, the method still depends on self-repair of the skin of the patient, and the skin damage repair efficiency is low.

Aiming at pressure sores, incontinent dermatitis, pressure skin lesions and the like of severe patients, a novel dressing which can resist bacteria outside the body, resist inflammation in the body, adapt to stress change at the periphery of the skin lesion position and can efficiently induce skin healing is needed to accelerate wound healing. Therefore, there is a strong clinical need to develop a new type of medical dressing that "wet" heals, inducing promotion of skin self-healing.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention aims to provide a three-dimensional structured biological dressing for repairing skin lesions of severe patients, which can release bioactive factors to promote the repair of the skin lesions and has a gradient three-dimensional network structure to ensure that the position of the skin lesions is in good contact with the dressing when the patients move.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows:

a three-dimensional structured biological dressing for repairing skin damage of severe patients comprises a back lining layer, a functional layer and a film coating layer, wherein the functional layer is adhered above the back lining layer, and the film coating layer is adhered above the functional layer; wherein the back lining layer is a flexible substrate and is made of gauze or biocompatible plastic; the functional layer comprises a matrix and a functional cell system; the film coating layer is made of flexible materials, including gauze or biocompatible plastics; the functional layer and the lining layer are strongly adhered and are fixedly combined together; the film coating layer and the functional layer are weakly adhered, and the film coating layer can be peeled off from the functional layer;

the functional layer is provided with three different functional cell layers along the thickness direction of the biological dressing respectively: a base layer, an intermediate layer and a surface layer; the basal layer close to the film coating layer is directly contacted with the skin damage part when in use, the thickness is 20-70 μm, and a cell layer which can be fused with cells of the dermis layer of the skin is adopted; the thickness of the middle layer is 50-100 μm, and a multicellular system and a growth factor capable of promoting the growth of the dermis layer are adopted; the thickness of the surface layer close to the back lining layer is 70-200 μm, and a multicellular system capable of promoting the growth of the epidermal layer is adopted; the base layer is attached to the film coating layer and is weakly adhered; the surface layer is attached to the back lining layer and is strongly adhered.

The inside of the functional layer is a three-dimensional network structure formed by support beams, and the diameter of each support beam is 5-50 mu m; the inside of each supporting beam is of a porous three-dimensional structure, and the characteristic dimension of the three-dimensional structure inside the supporting beam is 0.05-10 mu m.

Supporting beam demonstrate the gradient distribution in biological dressing thickness direction, supporting beam's distribution density changes along with the thickness from the bottom to the surface promptly, reduce gradually, the law that distribution density changes is confirmed by the dynamics simulation of patient skin damage position, the mechanics characteristic of embodiment is, when receiving bending stress or tensile stress, the stress state of skin damage position when patient moves promptly, biological dressing surface shape grow, and the bottom diminishes, thereby skin damage position stress/strain change when making biological dressing can initiatively adapt to patient's motion, the adhesion stability of reinforcing biological dressing and skin damage position, avoid the skin damage position secondary damage that causes because of the dressing drops in the patient motion process.

The base material of the support beam is a hydrogel system mixed with nutrient raw materials, and the hydrogel system comprises a sodium alginate/gelatin hydrogel system, a polyion composite hydrogel system or a polyethylene glycol composite hydrogel system; the matrix material is a porous three-dimensional structure, is used for cell differentiation, proliferation, nutrient raw material transmission and adaptation to the stress of skin injury positions of patients during movement, can preserve moisture and provides a wet healing environment for skin injury wound surfaces.

A functional cell system is prefabricated in the substrate material of the support beam, and the functional cell system is localized and distributed in multiple cells in the substrate; cells include fibroblasts, stem cells or skin keratinocytes; the functional cell system can be combined with skin, and can release corresponding active factors to induce skin damage repair; in order to support cell differentiation and proliferation, a functional cell system contains nutrient raw materials, and the nutrient raw materials comprise collagen, alginate or monmorized silk fibroin derivatives.

The matrix material of the support beam adopts a polyethylene glycol composite hydrogel system, and the matrix is degraded along with time in the skin lesion healing process; the polyion composite hydrogel system is adopted, the matrix is degraded and separated from the skin lesion part under external stimulation in the skin lesion healing process or after the skin lesion healing is finished, and the external stimulation is electric field action, ultraviolet irradiation or infrared irradiation.

The porous three-dimensional structure of the base material is a three-dimensional structure with a pre-designed shape, and is designed and manufactured in a manual manufacturing mode, wherein the manual manufacturing mode comprises 3D printing or molding; or the porous and multi-component characteristics of the hydrogel material are utilized, and one component of the hydrogel material is removed during manufacturing to form the porous characteristic, for example, the water in the hydrogel matrix is removed by adopting a freeze drying method.

The cells in the functional cell system are living cells and can be differentiated, proliferated and migrated; the nutrient raw material is a material capable of supporting living cells.

The three-dimensional structures of the base materials are mutually connected in bulk, and no closed cavity exists; the cells are attached to the surface of the three-dimensional structure for growth, differentiation and proliferation; and nutrient raw materials are conveyed along the three-dimensional structure.

The invention has the advantages that: the invention is based on the composition of multilayer living cells of skin-like tissues, has biological activity, and can perform biological activity exchange and mutual promotion of growth with self cells at the skin lesion position of a patient; the biological dressing can release bioactive factors, thereby inducing the self-repair of skin at the skin lesion site. On the other hand, biological dressing has the three-dimensional network structure of gradualization, can initiatively adapt to the stress state of patient's motion in-process skin damage position to skin damage position and the good contact of this biological dressing when guaranteeing the patient motion, thereby guarantee validity and the reliability that this biological dressing is restoreed to the skin damage.

Drawings

Fig. 1 is a schematic structural diagram of a biological dressing of the present invention.

Fig. 2 is a schematic view showing the peeling of the coating layer 3 from the functional layer 2 in use of the biological dressing of the present invention.

Fig. 3 is a three-dimensional grid structure diagram in a functional layer of a biological dressing of the invention.

Fig. 4 is a schematic diagram of cells and growth factors in a functional layer of the biological dressing of the present invention.

Fig. 5 is a view showing the internal structure of a support beam in the functional layer of the biological dressing of the present invention.

Fig. 6 is a schematic view of the deformation of a functional layer under external stress when using a biological dressing according to the invention.

Detailed Description

The invention is described in detail below with reference to the figures and examples.

As shown in fig. 1, the three-dimensional structured biological dressing for repairing the skin damage of the critically ill patient consists of a backing layer 1, a functional layer 2 and a film coating layer 3, wherein the functional layer 2 is adhered above the backing layer 1, and the film coating layer 3 is adhered above the functional layer 2; wherein the backing layer 1 is a flexible substrate made of gauze or biocompatible plastic and provides support for the biological dressing; the functional layer 2 comprises a matrix and a functional cell system; the film coating layer 3 is made of flexible materials, including gauze or biocompatible plastics;

the functional layer 2 is divided into 3 layers according to functions: a base layer 4 with the thickness of 20-70 μm, a middle layer 5 with the thickness of 50-100 μm and a surface layer 6 with the thickness of 70-200 μm, wherein the base layer 4 is attached to the coating layer 3 and is weakly adhered; the surface layer 6 is attached to the backing layer 1 for strong adhesion.

As shown in fig. 2, in use, the coating layer 3 is peeled off from the functional layer 2, the base layer 4 in the functional layer 2 is exposed, the base layer 4 is attached to the skin lesion of the patient, and after the base layer 4 is closely attached to the skin lesion of the patient, the backing layer 1 of the biological dressing is fixed to the skin of the patient with a medical adhesive material such as an adhesive tape.

As shown in fig. 3, the interior of the functional layer 2 is a three-dimensional network structure, the three-dimensional network structure is composed of supporting beams 7, and the structural style can include various mechanical structures (such as regular tetrahedron structures, face-centered cubic structures, etc.); the density of the support beams 7 in the base layer 4 is greater than that of the support beams 7 in the intermediate layer 5, and the density of the support beams 7 in the intermediate layer 5 is greater than that of the support beams 7 in the surface layer 6, i.e., the density of the three-dimensional network structure in the base layer 4 is greater than that in the intermediate layer 5, and the density of the three-dimensional network structure in the intermediate layer 5 is greater than that in the surface layer 6.

The base material of the support beam 7 is a hydrogel system mixed with nutrient raw materials, the diameter of the hydrogel system is 5-50 microns, the hydrogel system comprises but is not limited to a sodium alginate/gelatin hydrogel system, a polyion composite hydrogel system, a polyethylene glycol composite hydrogel system and the like, and the hydrogel system has biocompatibility and can be gradually degraded during skin damage repair; the matrix material is a porous three-dimensional structure, is used for cell differentiation, proliferation, nutrient raw material transmission and adaptation to the stress of skin injury positions of patients during movement, can preserve moisture and provides a wet healing environment for skin injury wound surfaces; the matrix is used as a cell carrier and can effectively transmit nutrients required by cell differentiation and proliferation. Nutrient raw materials comprise but are not limited to collagen, alginate, monument fibroin derivatives and the like, and the matrix material of the support beam 7 has a degradable function and is degraded slowly with time or under external stimulation.

As shown in fig. 4, a functional cell system 8, a growth factor 9 and a corresponding nutrient raw material 10 are attached to the surface of the three-dimensional network structure inside the functional layer 2, and the functional cell system 8 is represented as different cell systems in the base layer 4, the intermediate layer 5 and the surface layer 6: in the base layer 4, the functional cell system 8 is a cell layer capable of fusing with cells of the dermal layer of the skin, such as skin fibroblasts, umbilical cord blood stem cells and the like; in the middle layer 5, the functional cell system 8 is a cell system capable of promoting the growth of the dermis, such as cord blood stem cells, slow-release basic fibroblast growth factors and the like; in the top layer 6, the functional cell system 8 is a cell system capable of promoting the growth of the epidermal layer, such as keratinocytes; the growth factors 9 and the nutrient raw materials 10 are attached to the surfaces of the supporting beams 7 in the base layer 4, the middle layer 5 and the surface layer 6, so that the normal growth of the functional cell system 8 in each level is ensured and promoted.

As shown in fig. 5, the support beam 7 has a three-dimensional structure therein, and the characteristic dimension of the three-dimensional structure therein is 0.05 μm to 10 μm; in the internal three-dimensional structure of the support beam 7, there is no closed chamber; on the surface of the internal three-dimensional structure of the support beam 7, a functional cell system 8, an oxidation raw material 10 and a growth factor 9 are adherently grown or adhered.

As shown in fig. 6, when in use, if the biological dressing is subjected to external stress 12, because the three-dimensional network structure of the functional layer 2 is in gradient distribution, the deformation of the biological dressing is that the deformation of the surface layer 6 is much larger than that of the base layer 4, that is, almost no interface slippage exists between the base layer 4 and the skin damage part 11 of the patient, and under the action of the external stress, the strain of the biological dressing is mainly reflected as the strain of the surface layer 6, so that the risk of separation of the biological dressing from the skin damage part caused by the movement of the patient is reduced.

Claims

1. The utility model provides a towards three-dimensional structured biological dressing that severe patient's skin damage was restoreed which characterized in that: the multifunctional leather consists of a back lining layer, a functional layer and a film coating layer, wherein the functional layer is adhered above the back lining layer, and the film coating layer is adhered above the functional layer; wherein the back lining layer is a flexible substrate and is made of gauze or biocompatible plastic; the functional layer comprises a matrix and a functional cell system; the film coating layer is made of flexible materials, including gauze or biocompatible plastics; the functional layer and the lining layer are strongly adhered and are fixedly combined together; the film coating layer and the functional layer are weakly adhered, and the film coating layer can be peeled off from the functional layer;

2. The three-dimensional structured biological dressing for severe patient skin lesion repair according to claim 1, wherein: the inside of the functional layer is a three-dimensional network structure formed by support beams, and the diameter of each support beam is 5-50 mu m; the inside of each supporting beam is of a porous three-dimensional structure, and the characteristic dimension of the three-dimensional structure inside the supporting beam is 0.05-10 mu m.

3. The three-dimensional structured biological dressing for severe patient skin lesion repair according to claim 2, wherein: the supporting beam presents gradient distribution in the thickness direction of the biological dressing, namely the distribution density of the supporting beam is gradually reduced along with the thickness change from the bottom to the surface, the law of the distribution density change is determined by the dynamic simulation of the skin damage position of a patient, and the embodied mechanical characteristics are that when the supporting beam is subjected to bending stress or tensile stress, namely the stress state of the skin damage position when the patient moves, the surface shape of the biological dressing is larger, and the bottom part is smaller, so that the biological dressing can actively adapt to the stress/strain change of the skin damage position when the patient moves.

4. The three-dimensional structured biological dressing for severe patient skin lesion repair according to claim 2, wherein: the base material of the support beam is a hydrogel system mixed with nutrient raw materials, and the hydrogel system comprises a sodium alginate/gelatin hydrogel system, a polyion composite hydrogel system or a polyethylene glycol composite hydrogel system; the matrix material is a porous three-dimensional structure and provides a wet healing environment for the skin injury wound.

5. The three-dimensional structured biological dressing for severe patient skin lesion repair according to claim 2, wherein: a functional cell system is prefabricated in the substrate material of the support beam, and the functional cell system is localized and distributed in multiple cells in the substrate; cells include fibroblasts, stem cells or skin keratinocytes; the functional cell system can be combined with skin, and can release corresponding active factors to induce skin damage repair; the functional cell system contains nutrient raw materials, and the nutrient raw materials comprise collagen, alginate or an fosemized silk fibroin derivative.

6. The three-dimensional structured biological dressing for severe patient skin lesion repair according to claim 4, wherein: the matrix material of the support beam adopts a polyethylene glycol composite hydrogel system, and the matrix is degraded along with time in the skin lesion healing process; the polyion composite hydrogel system is adopted, the matrix is degraded and separated from the skin lesion part under external stimulation in the skin lesion healing process or after the skin lesion healing is finished, and the external stimulation is electric field action, ultraviolet irradiation or infrared irradiation.

7. The three-dimensional structured biological dressing for severe patient skin lesion repair according to claim 4, wherein: the porous three-dimensional structure of the base material is a three-dimensional structure with a pre-designed shape, and is designed and manufactured in a manual manufacturing mode, wherein the manual manufacturing mode comprises 3D printing or molding; or a porous feature formed by removing one of the components of the hydrogel-based material during manufacture, using the porous, multi-component features of the material itself.

8. The three-dimensional structured biological dressing for severe patient skin lesion repair according to claim 5, wherein: the cells in the functional cell system are living cells and can be differentiated, proliferated and migrated; the nutrient raw material is a material capable of supporting living cells.

9. The three-dimensional structured biological dressing for severe patient skin lesion repair according to claim 5, wherein: the three-dimensional structures of the base materials are mutually connected in bulk, and no closed cavity exists; the cells are attached to the surface of the three-dimensional structure for growth, differentiation and proliferation; and nutrient raw materials are conveyed along the three-dimensional structure.