A controllably degradable biomaterial for external scleral pressure and a method for preparing the same

Abstract

The application discloses a controllable degradation biomaterial for scleral external pressure, relates to the technical field of medical biomaterials, and is mainly prepared by blending polylactic acid-glycolic acid copolymer (PLGA), polycaprolactone (PCL), hyaluronic acid, collagen type I and glycerol according to mass percentage. The biomaterial can realize time-controllable degradation, precise adaptation and graded degradation, and matches the supporting time required by retinal hole closure, frozen / laser spot maturation and retinal repositioning. The controllable degradation biomaterial has good biocompatibility, no immunogenicity, no rejection reaction, no inflammation stimulation and no toxicity.

Description

Technical Field

[0001] This invention relates to the field of medical biomaterials technology, specifically to a controllable degradable biomaterial for scleral compression surgery and its preparation method. Background Technology

[0002] Scleral tamponade is a classic surgical procedure for treating retinal detachment, and silicone sponge and silicone tape are commonly used as the external compression materials in clinical practice. These materials are non-degradable and can easily lead to problems such as local deformation of the eyeball, refractive changes, visual distortion, tissue adhesion, rejection reaction, and material exposure due to long-term retention, which seriously affect postoperative recovery and secondary surgical procedures.

[0003] Existing biodegradable ophthalmic materials mostly have a single degradation cycle, which cannot match the support time required for different retinal tears, degrees of detachment, and vitreous conditions. Furthermore, their formulation systems, mechanical properties, and biocompatibility do not meet the long-term stable support requirements of scleral compression. Therefore, there is an urgent need to develop a dedicated scleral compression material that is non-toxic, inert, biocompatible, allows for controllable degradation time according to clinical needs, is mechanically stable, leaves no residue after degradation, prevents adhesion, and facilitates secondary surgery. Summary of the Invention

[0004] This invention aims to overcome the shortcomings of existing technologies and provide a controllable degradable biomaterial and its preparation method that is mechanically stable, biocompatible, anti-adhesive, and suitable for scleral compression surgery. It can precisely match the support cycle according to clinical needs and solve problems such as eyeball deformation, refractive abnormalities, adhesion, and rejection caused by long-term placement of traditional silicone materials.

[0005] The technical solution of this invention is as follows: a controllable degradable biomaterial for scleral compression surgery, wherein the biomaterial is mainly prepared by blending polylactic-co-glycolic acid copolymer (PLGA), polycaprolactone (PCL), hyaluronic acid, type I collagen, and glycerol in a certain mass percentage. Controllable degradation over 1 month, 2 months, 3 months, 6 months, and 12 months can be achieved by adjusting the formula to suit different retinal detachment conditions.

[0006] The biomaterials are divided into the following five formulations according to their degradation cycle: 1-month degradation type (small cracks, shallow detachment): PLGA (50:50 molar ratio of lactic acid to glycolic acid) 65%, PCL 20%, 10-200kDa hyaluronic acid 10%, type I collagen 3%, glycerol 2%; 2-month degradation type (moderate cracks, moderate detachment): PLGA (lactic acid to glycolic acid molar ratio 75:25) 55%, PCL 30%, 250-400kDa hyaluronic acid 10%, type I collagen 3%, glycerol 2%; 3-month degradation type (moderate to severe detachment, multiple pores): PLGA (lactic acid to glycolic acid molar ratio of 85:15) 45%, PCL 40%, 750-1000kDa hyaluronic acid 10%, type I collagen 3%, glycerol 2%; 6-month degradation type (giant tear, complex detachment, vitreous proliferation): PLGA (lactic acid to glycolic acid molar ratio of 90:10) 30%, PCL 55%, 2000-2200kDa hyaluronic acid 10%, type I collagen 3%, glycerol 2%; 12-month degradation type (old detachment, recurrent detachment, severe proliferation): PCL 75%, PLGA (lactic acid to glycolic acid molar ratio of 95:5) 10%, 2000-2200kDa hyaluronic acid 10%, type I collagen 3%, glycerol 2%.

[0007] This invention also provides a method for preparing the controllable degradable biomaterial, comprising the following steps: First, the raw materials are pretreated: PCL and PLGA are vacuum dried, hyaluronic acid and type I collagen are aseptically freeze-dried, and glycerin is autoclaved. Then, the raw materials are blended: the raw materials are mixed according to the formula ratio, melted and stirred at 120–150℃ for 15–30 minutes to mix evenly; then the raw materials are extruded or molded into strips or sheets with a thickness of 1–3 mm; then cross-linked at 4℃ for 24 hours to enhance mechanical stability; finally, ethylene oxide sterilization and aseptic sealing packaging are performed.

[0008] Clinical application method: During the operation, the material with the corresponding degradation cycle is selected according to the size of the retinal tear, the degree of detachment, and the condition of the vitreous body. After cutting, it is applied to the corresponding position of the external scleral tear and fixed with 6-0 absorbable sutures to form a stable pressure ridge. Cryotherapy or laser photocoagulation of the retinal tear is performed to promote retinal repositioning. The material degrades slowly after the operation and does not require a second surgery to remove it.

[0009] The beneficial effects of this invention are as follows: The biomaterial of this invention can achieve time-controlled degradation and precise adaptation for graded degradation, matching the support time required for retinal tear closure, cryo / laser spot maturation, and retinal repositioning; the controllable degradable biomaterial of this invention has good biocompatibility, is non-immunogenic, non-rejective, and non-inflammatory, and is safe and non-toxic for long-term placement. The controllable degradable biomaterial of this invention is mechanically stable and has a durable compressive ridge, maintaining ≥80% of its mechanical strength before degradation, maintaining the stability of the scleral external compressive ridge, without displacement or deformation; the biomaterial ultimately degrades into water and carbon dioxide, leaving no foreign matter residue; hyaluronic acid and collagen form a smooth interface, avoiding dense adhesion between the sclera and conjunctiva, facilitating secondary surgery; achieving complete degradation and anti-adhesion technical effects. The biomaterial can be cut and shaped during surgery to conform to the curvature of the sclera, providing good pressure effect, simple operation, and strong clinical applicability. Detailed Implementation

[0010] The present invention will be further described in detail below with reference to specific embodiments, but the present invention is not limited to the following specific embodiments.

[0011] Example 1 The formulation for a one-month degradable, controllable biomaterial for scleral compression surgery targeting small lacerations and shallow detachments is as follows: PLGA (lactic acid and glycolic acid molar ratio of 50:50) 65%, PCL 20%, 10% hyaluronic acid with a molecular weight of 10-200kDa, 3% type I collagen, and 2% glycerol; The preparation method includes the following steps: First, the raw materials are pretreated: PCL and PLGA are vacuum dried, hyaluronic acid and type I collagen are aseptically freeze-dried, and glycerin is autoclaved. Then, the raw materials are blended: the raw materials are mixed according to the formula ratio, melted and stirred at 120℃ for 15 minutes to mix evenly; then the raw materials are extruded or molded into strips with a thickness of 2mm; then cross-linked at 4℃ for 24 hours to enhance mechanical stability; finally, ethylene oxide sterilization and aseptic sealing packaging are performed.

[0012] Example 2 The formulation for a 2-month degradable, controllable biomaterial for scleral compression surgery targeting moderate scleral tears and moderate detachment is as follows: PLGA (lactic acid to glycolic acid molar ratio of 75:25) 55%, PCL 30%, 250-400kDa hyaluronic acid 10%, type I collagen 3%, and glycerol 2%. The preparation method includes the following steps: First, the raw materials are pretreated: PCL and PLGA are vacuum dried, hyaluronic acid and type I collagen are aseptically freeze-dried, and glycerin is autoclaved. Then, the raw materials are blended: the raw materials are mixed according to the formula ratio, melted and stirred at 150℃ for 30 minutes to mix evenly; then the raw materials are extruded or molded into strips with a thickness of 3mm; then cross-linked at 4℃ for 24 hours to enhance mechanical stability; finally, ethylene oxide sterilization and aseptic sealing packaging are performed.

[0013] Example 3 The formulation for a 3-month degradable, controllable biomaterial for scleral compression surgery targeting moderate to severe detachment and multiple tears is as follows: PLGA (lactic acid to glycolic acid molar ratio of 85:15) 45%, PCL 40%, 750-1000kDa hyaluronic acid 10%, type I collagen 3%, and glycerol 2%. The preparation method includes the following steps: First, the raw materials are pretreated: PCL and PLGA are vacuum dried, hyaluronic acid and type I collagen are aseptically freeze-dried, and glycerin is autoclaved. Then, the raw materials are blended: the raw materials are mixed according to the formula ratio, melted and stirred at 150℃ for 15 minutes to mix evenly; then the raw materials are extruded or molded into sheets with a thickness of 1mm; then cross-linked at 4℃ for 24 hours to enhance mechanical stability; finally, ethylene oxide sterilization and aseptic sealing packaging are performed.

[0014] Example 4 The formulation for a 6-month degradable, controllable degradable biomaterial for scleral pulsation, targeting large scleral tears, complex detachments, and vitreous proliferation, is as follows: PLGA (lactic acid to glycolic acid molar ratio of 90:10) 30%, PCL 55%, 2000-2200kDa hyaluronic acid 10%, type I collagen 3%, and glycerol 2%. The preparation method includes the following steps: First, the raw materials are pretreated: PCL and PLGA are vacuum dried, hyaluronic acid and type I collagen are aseptically freeze-dried, and glycerin is autoclaved. Then, the raw materials are blended: the raw materials are mixed according to the formula ratio, melted and stirred at 130℃ for 20 minutes to mix evenly; then the raw materials are extruded or molded into sheets with a thickness of 2mm; then cross-linked at 4℃ for 24 hours to enhance mechanical stability; finally, ethylene oxide sterilization and aseptic sealing packaging are performed.

[0015] Example 5 The formulation for a 12-month degradable, controllable degradable biomaterial for scleral compression surgery targeting old detachment, recurrent detachment, and severe proliferation is as follows: PCL 75%, PLGA (lactic acid to glycolic acid molar ratio of 95:5) 10%, 2000-2200kDa hyaluronic acid 10%, type I collagen 3%, and glycerol 2%.

[0016] The preparation method includes the following steps: First, the raw materials are pretreated: PCL and PLGA are vacuum dried, hyaluronic acid and type I collagen are aseptically freeze-dried, and glycerin is autoclaved. Then, the raw materials are blended: the raw materials are mixed according to the formula ratio, melted and stirred at 140℃ for 25 minutes to mix evenly; then the raw materials are extruded or molded into sheets with a thickness of 3mm; then cross-linked at 4℃ for 24 hours to enhance mechanical stability; finally, ethylene oxide sterilization and aseptic sealing packaging are performed.

[0017] The biomaterials of this invention can achieve time-controlled degradation and precise adaptation, with degradation cycles of 1-3 months, 6 months, and 12 months, matching the support time required for retinal tear closure, cryo / laser spot maturation, and retinal reattachment. Hyaluronic acid (HA) and type I collagen are both natural extracellular matrix components with excellent biocompatibility. Hyaluronic acid is a highly hydrophilic mucopolysaccharide that forms a highly viscoelastic gel in water, creating a hydration layer on the material surface and reducing non-specific adhesion of proteins and cells. Type I collagen provides cell recognition sites, promoting benign integration of the material with host tissues rather than dense adhesion.

[0018] When the two are combined, the hydration layer of hyaluronic acid acts as a "barrier," preventing excessive proliferation of fibroblasts and excessive deposition of collagen on the material surface, thereby avoiding the dense adhesion of the sclera and conjunctiva that is common in traditional silicone materials.

[0019] The above are merely exemplary embodiments of the present invention and do not constitute any limitation on the scope of protection of the present invention. All technical solutions formed by equivalent exchange or substitution fall within the scope of protection of the present invention.

Claims

1. A controllable degradable biomaterial for scleral compression surgery, characterized in that, The biomaterial is mainly prepared by blending polylactic acid-glycolic acid copolymer (PLGA), polycaprolactone (PCL), hyaluronic acid, type I collagen, and glycerol in a certain mass percentage.

2. The controllable degradable biomaterial for scleral compression surgery according to claim 1, characterized in that, By adjusting the formula, controlled degradation can be achieved over 1 month, 2 months, 3 months, 6 months, and 12 months, adapting to the needs of different retinal detachment conditions.

3. The controllable degradable biomaterial for scleral compression surgery according to claim 2, characterized in that, The biomaterial has a 1-month degradation cycle formulation as follows: PLGA (lactic acid and glycolic acid molar ratio of 50:50) 65%, PCL 20%, 10% hyaluronic acid with a molecular weight of 10-200kDa, 3% type I collagen, and 2% glycerol.

4. The controllable degradable biomaterial for scleral compression surgery according to claim 2, characterized in that, The biomaterial has a 2-month degradation cycle formulation as follows: PLGA (lactic acid to glycolic acid molar ratio of 75:25) 55%, PCL 30%, 250-400kDa hyaluronic acid 10%, type I collagen 3%, and glycerol 2%.

5. The controllable degradable biomaterial for scleral compression surgery according to claim 2, characterized in that, The biomaterial has a 3-month degradation cycle formulation as follows: PLGA (lactic acid to glycolic acid molar ratio of 85:15) 45%, PCL 40%, 750-1000kDa hyaluronic acid 10%, type I collagen 3%, and glycerol 2%.

6. The controllable degradable biomaterial for scleral compression surgery according to claim 2, characterized in that, The biomaterial has a 6-month degradation cycle and the following formulation: PLGA (lactic acid to glycolic acid molar ratio of 90:10) 30%, PCL 55%, 2000-2200kDa hyaluronic acid 10%, type I collagen 3%, and glycerol 2%.

7. The controllable degradable biomaterial for scleral compression surgery according to claim 2, characterized in that, The biomaterial has a 12-month degradation cycle formulation as follows: PCL 75%, PLGA (lactic acid to glycolic acid molar ratio of 95:5) 10%, 2000-2200kDa hyaluronic acid 10%, type I collagen 3%, and glycerol 2%.

8. The controllable degradable biomaterial for scleral compression surgery according to claim 1, characterized in that, The method for preparing the controllable degradable biomaterial includes the following steps: First, the raw materials are pretreated: PCL and PLGA are vacuum dried, hyaluronic acid and type I collagen are aseptically freeze-dried, and glycerin is autoclaved. Then, the raw materials are blended: the raw materials are mixed according to the formula ratio, melt-stirred at 120–150℃ for 15–30 minutes to achieve uniform mixing. The raw materials are then extruded or molded into strips or sheets with a thickness of 1–3 mm. Then, they are cross-linked at 4℃ for 24 hours to enhance mechanical stability. Finally, they are sterilized with ethylene oxide and aseptically sealed and packaged.