Anterior Cruciate Ligament Reconstruction Surgery: Creating a Permissive Healing Phenotype in Military Personnel and Civilians for Faster Recovery

Abstract

Introduction Anterior cruciate ligament (ACL) rupture in military personnel and civilians can be a devastating injury. A service member is 10 times more likely to suffer an ACL injury than their civilian counterparts, and despite successful surgical stabilization, 4%-35% will develop arthrofibrosis, over 50% will not return to full active duty, and up to 50% will develop post-traumatic osteoarthritis (PTOA) within 15 years. Equally concerning, woman are 2 to 8 times more likely to experience ACL injuries than men, which represents a major knowledge gap. Materials and Methods A comprehensive literature search was performed in December 2021 using structured search terms related to prevalence, risk factors, disease progression, and treatment of ACL injury and reconstruction. The literature search was conducted independently by two researchers using PubMed, Cochrane, and Embase databases, with inclusion of articles with military, civilian, and sex relevance, and exclusion of most papers with a publication date greater than 10 years. The resources used for the review reflect the most current data, knowledge, and recommendations associated with research and clinical findings from reliable international sources. Results Currently, there is no effective system-based drug therapy that creates a “permissive environment” to reduce synovial and cartilage stress after ACL injury and reconstruction and prevent secondary complications. We argue that progress in this area has been hampered by researchers and clinicians failing to recognize that (1) an ACL injury is a system’s failure that affects the whole joint, (2) the early molecular events define and perpetuate different injury phenotypes, (3) male and female responses may be different and have a molecular basis, (4) the female phenotype continues to be under-represented in basic and clinical research, and (5) the variable outcomes may be perpetuated by the trauma of surgery itself. The early molecular events after ACL injury are characterized by an overexpression of joint inflammation, immune dysfunction, and trauma-induced synovial stress. We are developing an upstream adenosine, lidocaine, and magnesium therapy to blunt these early molecular events and expedite healing with less arthrofibrosis and early PTOA complications. Conclusions ACL injuries continue to be a major concern among military personnel and civilians and represent a significant loss in command readiness and quality of life. The lack of predictability in outcomes after ACL repair or reconstruction underscores the need for new joint protection therapies. The male–female disparity requires urgent investigation.

Female rats have a different healing phenotype than males after anterior cruciate ligament rupture with no intervention

“…The effect of sex on joint tissue repair processes following an ACL rupture are poorly understood ( 2 ). We report in a rat model of non-surgical ACL rupture: (1) both sexes showed similar functional responses early after ACL rupture, however, females had persistent mechanical hyperalgesia; (2) males and females showed different hematological and systemic inflammatory responses over 31-days; (3) males had significantly higher levels of VEGF, RANTES and IP-10 chemokines in synovial fluid compared to females; (4) Acta2 gene expression (α-SMA production) in the ACL remnant was significantly higher in males with no change in females; and (5) sex differences in ECM remodeling were also apparent in the IFP and articular cartilage.…”

“…Anterior cruciate ligament (ACL) rupture is one of the most debilitating musculoskeletal injuries and typically occurs following excessive rotational stresses and/or extreme deceleration forces (1,2). Globally, there are over 2 million ACL injuries each year, with annual incidence rates continuing to rise, particularly in the young (2)(3)(4)(5).…”

“…Anterior cruciate ligament (ACL) rupture is one of the most debilitating musculoskeletal injuries and typically occurs following excessive rotational stresses and/or extreme deceleration forces (1,2). Globally, there are over 2 million ACL injuries each year, with annual incidence rates continuing to rise, particularly in the young (2)(3)(4)(5). Although females are 2 to 8 times at higher risk for ACL injuries than men (6)(7)(8), it is not known if there are sex differences during early healing following a rupture (2,(6)(7)(8)(9).…”

“…Globally, there are over 2 million ACL injuries each year, with annual incidence rates continuing to rise, particularly in the young (2)(3)(4)(5). Although females are 2 to 8 times at higher risk for ACL injuries than men (6)(7)(8), it is not known if there are sex differences during early healing following a rupture (2,(6)(7)(8)(9). Some studies indicate that females may be more susceptible to functional deficits after ACL reconstruction (ACLR) surgery than men (10,11), however, few studies have focused on the impact of sex on early healing.…”

Postoperative complications following ACL reconstruction: Prevention and management

“…The patient who demonstrates significant fear may benefit from postponing the protocol's progression, receiving information to boost patient self-efficacy, and implementing neuromuscular re-education approaches such as perturbation training. It has been demonstrated that kinesiophobia and pain catastrophizing are two psychological characteristics significantly associated with not returning to sport [40,41] .…”