Preparation Of PDGF-BB Nanocapsule With Controlled Release Property For Enhanced Wound Healing

Wound healing is generally carried out in an orderly manner according to the four stages of hemostasis,inflammation,proliferation,and remodeling.However,due to some biological/pathological reasons,the wound is stagnant in the inflammatory stage and cannot enter the next stage,forming a chronic wound.Taking diabetic ulcers as an example,China has the largest number of adults with diabetes in 2019,with medical-related expenditures of $109 billion.Growth factors such as PDGF play an important role in wound healing.However,like most protein drugs,growth factors are unstable and easily deactivated by enzymes,which leads to their inability to maintain a stable concentration in the wound area for a long time,and single administration cannot significantly promote wound repair.However,repeated high-doses administration is costly and will cause side effects.Because chronic wound healing is a long-lasting process,the development of strategies to improve the stability and controlled release of growth factors is critical for the better application of growth factors to wound healing.We synthesized a nanocarrier called n(PDGF-BB)by in-situ free radical polymerization for the controlled release of PDGF-BB and full-thickness wound treatment in diabetic mice.With a mild reaction conditions,growth factors are encapsulated in polymer shells,which prevents enzyme from degradation and improves stability,without losing activity.The obtained nanocapsules have a spherical structure with a particle size of about 25 nm,and by adjusting the components of the nanocapsule,it can respond to the chronic wound microenvironment and achieve a controlled long-term PDGF-BB release to meet the need for wound repair.Thenanocapsules are dispersed in a temperature-sensitive hydrogel to fix thedrug to the wound.We constructed a diabetic mouse model by a singlehigh-dose intraperitoneal injection of streptozocin,and randomly selected micewith blood glucose>16.7 mmol/L to construct a full-thickness skin wound model.After administration,the wound healing was observed withina certain time interval.It was found that the average wound area of miceadministered n(PDGF-BB)dropped to 7.8%within 14 days(54.9%and 25.1%for PBS and PDGF-BB,respectively),the epidermis and dermis were intact,more collagen deposition and new blood vessel formation were observed.For further use,we can also encapsulate different growth factors for tissue regeneration,bone repair and other diseases,and adjust the components to respond to different microenvironments to achieve targeted drug delivery.