Injectable amniotic membrane/umbilical cord particulate for facet joint syndrome: A retrospective,single-center study

Abstract

BACKGROUND:

Facet joint syndrome (FJS) pain is a significant contributor to back pain and has a high rate of opioid prescription. Unfortunately, there are a limited number of therapeutic options for these patients.

OBJECTIVE:

To evaluate the safety and effectiveness of amniotic membrane/umbilical cord particulate (AM/UC) in managing FJS pain.

METHODS:

A single-center, investigator-initiated, retrospective study was performed on consecutive patients with FJS pain who received intra- or peri-articular injection of AM/UC between July 1, 2018 and July 26, 2019. Primary outcome was change in Patient Global Impression of Change (PGIC) at 6 weeks, 3 months, 6 months, and 12 months to assess the self-reported percent improvement relative to baseline. Safety was assessed by AM/UC- and procedure-related complications. Paired $t$ -tests were used to determine whether there is a statistically significant improvement of pain post-injection compared to baseline.

RESULTS:

There were a total of 54 patients (69.7 $\pm$ 13.4 years; 31 female) presenting baseline pain score of 9.2 $\pm$ 1.0 despite prior treatments of activity modification (66.7%), NSAIDs (61.1%), opioids (37.0%), and physical therapy (35.2%). Mean GPIC improvement was 65.3%, 67.5%, 56.9%, and 56.7% among responders ${}_{30}$ , respectively. There were no complications.

CONCLUSION:

This study supports the safety and effectiveness of AM/UC particulate injection in managing FJS pain.

Keywords

Amniotic chronic low back facet pain umbilical cord

1. Introduction

Chronic low back pain (LBP) is a significant contributor to human morbidity, affecting an estimated 40% of people globally at some point in their lives with an increased risk among the aging population [1]. In 2012, approximately 52.3 million patients visited healthcare providers with a complaint of back pain in the United States, a significant increase from 44.6 million visits in 2004 [2]. Among various different causes of LBP, facet joint syndrome (FJS) accounts for an estimated 15–45% of all LBP cases [3] and manifests as a result of natural weathering and abnormal body mechanics [4, 5, 6]. FJS is a condition in which the joints are a source of pain and the pain is often felt during initial movement after rest and exacerbated by twisting motions. As such, FJS itself is a significant contributor to pain and impairs physical function, especially among the aging population with LBP.

There are currently few effective conservative treatment modalities for FJS and are generally palliative. Physical therapy, activity modification, and analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioids are commonly employed but tend to provide only temporary pain relief [7, 8, 9]. After approximately three months of conservative treatment without response [10], patients usually undergo minimally invasive procedures such intraarticular, periarticular, or nerve branch blocks with local anesthetics and/or corticosteroids. Articular FJ injections are not widely supported by National guidelines [11] whereas therapeutic nerve blocks generally provide relief for 15–19 weeks with one injection [7, 12]. Once improvements are no longer attained with branch blocks, radiofrequency ablation (RFA) is commonly performed in select patients to burn or ablate the nerves and quiet the pain response [7, 13, 14]. However, this pain relief is temporary as 76% of patients undergoing RFA report $\geqslant$ 50% improvement in pain at 7–21 days post-ablation, and the proportion of responders decrease to 32% and 22% at 6-month and 1-year, respectively, presumably due to the nerve re-growing and the pain response returning [13].

Recently, the use of biological therapies to treat chronic, painful conditions has become increasingly popular. In particular, placenta-derived products, including amniotic membrane and umbilical cord (AM/UC) tissues, are currently being investigated given their commercial availability, long history of safe use, and their known anti-inflammatory, anti-scarring, and pro-regenerative properties [15, 16, 17, 18]. In a retrospective review, Bennett et al. [19] showed that intra-articular injection of AM/UC particulate into facet joints of 9 patients reduced pain from 8.2 at baseline to 0.4 by 6-months post-treatment. Additionally, all patients had ceased use of prescription pain medications, including opioids in 4 patients, after receiving AM/UC [19]. Furthermore, we have shown AM/UC particulate provided significant pain reduction and improved physical function in a prospective study of 20 patients with knee osteoarthritis, conceptually resembling FJS with imbalanced repair of degenerative joint tissues [20, 21]. Given these encouraging findings, we performed a retrospective chart review on a large patient cohort to determine whether injection of AM/UC particulate provides significant and long-lasting pain relief in FJS patients.

2. Methods

Following IRB review exemption and waiver of authorization by Sterling IRB, a retrospective review was performed on consecutive patients receiving articular injection of AM/UC particulate for FJS pain by a single physician (pain management specialist with 34 years of experience) between July 1, 2018 and July 26, 2019 at the primary author’s practice. In accordance with the Declaration of Helsinki and HIPPA, only minimum necessary data were extracted from electronic medical records, which included age, gender, body mass index (BMI), comorbidities, duration of symptoms, prior surgeries, medication use, and outcome measures.

2.1 Patients

Patients were eligible for inclusion if they received articular injection of particulate AM/UC for FJS pain within the time-period established above. Patients were excluded from this study if they received concomitant treatment for other spinal pathology, had dementia, or had no follow-up records. Diagnosis of FJS pain was confirmed by MRI or radiographs read by a radiology sub-specialist at an independent diagnostic testing facility and positive diagnostic anesthetic block testing [22, 23, 24].

2.2 Treatment with AM/UC

The AM/UC particulate (CLARIX ${}^{\@setsize{\scriptsize}{8pt}{\viipt}{\@viipt}{\textregistered}}$ Flo, Amniox Medical, Miami, FL, USA) is derived from donated human placental tissue following healthy, live, caesarian section, full-term births. Under aseptic conditions, AM and UC are retrieved from the placenta and cleared of blood followed by lyophilization, micronization, and terminal sterilization. During this process, all living cells are devitalized while the tissues’ natural biological characteristics including its anti-inflammatory properties are preserved [18] The final AM/UC product is a particulate powder and available at 25, 50, and 100 mg per vial.

All facet injections were performed under fluoroscopic guidance and under light conscious sedation (Midazolam and Fentanyl) following the current guidelines with non-invasive monitoring [25]. Before injection, patients received local anesthetic (1% lidocaine) by raising a skin wheal and going down to the hub of a 27-guage 1.25 in needle at each spinal level. A 22-guage 3.5-inch Quincke needle was then introduced into each facet joint if possible (periarticular otherwise). Following negative aspiration to make sure there was no intravascular placement, Omniplaque 240 (GE Healthcare, Chicago, IL, USA) was injected to confirm designated injection space and no vascular runoff. Particulate AM/UC was then injected slowly at the affected levels. The entire procedure generally took roughly 15 minutes.

2.3 Post-injection care

Patient was discharged from conscious sedation to the care of their caretaker when they felt normal without drowsiness or pain (usually 10–15 minutes). Patient was told not to drive for the next 12 hours after the procedure due to sedation. If the patient suffered any post-procedure pain, they were instructed to take ibuprofen (Advil liquid gel) q6 hours or acetaminophen (APAP) 325 mg q6 hrs in case of allergy to NSAIDs. Patients were instructed to rest the day of the procedure and resume activities of daily living the next day however avoiding strenuous sport and recreational activities for 10 days or avoid returning to work if their pain was above 4 out of 10.

2.4 Outcome measures

Numerical Pain Rating Scale (NPRS) score was used to document patient’s pain at baseline, in which patients reported the average severity of their pain on a 11-point scale, ranging from “no pain” at 0 to “worst imaginable pain” at 10. At follow-up visits, patients provided self-reported Patient Global Impression of Change (PGIC), which is expressed as percent improvement following treatment relative to baseline, and is used to quantify the degree of symptomatic change in pain and function at follow-up as reported [26]. Additionally, patients were classified as responders to treatment if they achieved at least 30% improvement at their first follow-up visit and non-responders if they achieved less than 30% as a 30% improvement in pain is considered clinically significant [27, 28, 29]. Pain improvement of at least 50% was similarly assessed as it is considered the pain improvement threshold for RFA [13, 14, 28]. Outcomes were reported at 6-weeks, 3-months, 6-months, and 12-months post-injection. We defined responders as patients who reported pain relief of at least 30% and 50% (responders ${}_{30}$ and responders ${}_{50}$ ) at their first follow-up appointment. Conversely, non-responders were patients who reported relief of less than 30% and 50% (non-responders ${}_{30}$ and non-responders ${}_{50}$ ).

2.5 Statistical analysis

All statistical analyses were performed in R version 3.6.2 and R-Studio version 1.2.5033. Categorical variables were described with percentages and frequencies, while continuous variables were described with mean $\pm$ standard deviation or median (range). Paired $t$ -tests were used to determine whether there is a statistically significant improvement of pain at follow-ups compared to baseline. The nominal $\alpha=$ 0.05 was considered significant ( $p<$ 0.05). Additionally, we assessed whether there is a difference in demographics and/or comorbidities between responders or non-responders.

3. Results

A total of 54 patients met the eligibility criteria and were included in the final analysis. Twenty-one patients were excluded because they received concomitant ozone treatment for discogenic pain ( $n=$ 3), received concomitant epidural adhesiolysis ( $n=$ 1), had dementia ( $n=$ 1), had no follow-up ( $n=$ 11), had follow-up but no postoperative self-reported PGIC/pain score ( $n=$ 6) or had prior back surgery ( $n=$ 9). The mean patient age was 69.7 $\pm$ 13.4 years, with 42.6% (23/54) and 57.4% (31/54) being male and female, respectively. The patients average BMI was 27.7 $\pm$ 3.3 kg/m ${}^{2}$ . These 54 patients exhibited comorbidities such as hypertension (32%), stenosis (15%), diabetes mellitus (11%), hyperlipidemia (7%), and thyroid conditions (7%). At baseline, the mean patient pain score was 9.2 $\pm$ 1.0 out of 10 with a duration of 6.5 $\pm$ 4.1 years despite previous management with activation modification (66.7%), NSAIDs (61.1%), opioids (37.0%), and physical therapy (35.2%).

The AM/UC injection was performed uneventfully in all cases at lumbar (70%), cervical (17%), cervical-thoracic (11%), and sacral (2%) injection sites. Patients received one (6%), three (72%) or four (22%) levels of injection. This corresponded to majority of patients receiving 16.7 mg and 12.5 mg of AM/UC per joint.

After AM/UC injection, the average PGIC was 48.0% at 6 weeks, 53.5% at 3 months, 58.9% at 6 months, and 56.7% at 12 months. There were 38 (70.8%) responders ${}_{30}$ and 31 (57.4%) responders ${}_{50}$ . Mean GPIC improvement was 65.3%, 67.5%, 56.9%, 56.7% among responders ${}_{30}$ and 72.2%, 69.6%, 65.0%, 45.0% among responders ${}_{50}$ at 6 weeks, 3 months, 6 months, and 12 months, respectively. Non-responders average GPIC improvement was 6.5 $\pm$ 8.0% at 6 weeks. The proportion of patients using NSAIDs decreased from 33/54 (61.1%) to 17/54 (31.5%) ( $p<$ 0.01) while the proportion using opioids was the same (37.0%, 20/54) ( $p\sim$ 1.0). Patients that had $\geqslant$ 50% improvement were older than those patients that did not have such improvement (74.8 vs. 67.5 years respectively, $p=$ 0.04). Gender, BMI, co-morbidities, and prior treatments did not have statistically significant associations with patient response (Tables 1 and 2). There were also no complications or adverse events observed based on clinical evaluation or reported by patients that were attributed to the injection of AM/UC over the 12-month duration.

Table 1
Association between demographics and response to treatment

Characteristic	Value/%	Responders ${}_{30}$ ( $P$ -value)	Responders ${}_{50}$ ( $P$ -value)
Mean age in years (SD)	69.7 (13.4)	0.09	0.04
BMI (kg/m ${}^{2}$ ), # (%)	27.7 (3.3)	0.25	0.27
Underweight $<$ 18.5	0%
Normal $=$ 18.5–24.9	31.2%
Overweight $=$ 25.0–29.9	31.2%
Obese $\geqslant$ 30	37.5%	$\sim 1$	0.31
Gender, # (%)		$\sim 1$	0.70
Male	23 (42.6)
Female	31 (57.4)

Table 2

Association between comorbidities and response to treatment

Comorbidity	N (54)	%	Responders ${}_{30}$ ( $P$ -value)	Responders ${}_{50}$ ( $P$ -value)
Hypertension	17	31.5	0.11	0.18
Diabetes	6	11.1	0.06	0.38
High lipid/cholesterol	4	7.4	0.31	0.63
Thyroid condition	4	7.4	0.31	0.13
GERD	3	5.6	0.55	0.25
Heartburn	3	5.6	0.55	0.25
Lymphedema	1	1.9	$\sim$ 1	$\sim$ 1
Cardiac condition	1	1.9	0.30	0.43
Cancer	1	1.9	$\sim$ 1	$\sim$ 1
Hip pain	1	1.9	0.30	0.43
Asthma	1	1.9	$\sim$ 1	$\sim$ 1
Avascular necrosis	1	1.9	$\sim$ 1	$\sim$ 1

4. Discussion

FJS pain is a significant contributor to back pain and has a high rate of opioid prescription [30]. Unfortunately, there are a limited number of therapeutic options for these patients. FJS is characterized by chronic inflammation due to age-related degenerative process [7]. Several inflammatory cytokines are involved including IL-6, IL-7, IL-13, TNF- $\alpha$ , and PDGF that may bind nerve receptors and illicit a pain response [31, 32]. This may explain why a subpopulation of patients with inflammation benefit for an intermediate-term from intra-articular steroid injections. This retrospective study showed that AM/UC injection is safe and effective in relieving FJS pain in 54 eligible patients despite prior management with activation modification, NSAIDs, opioids, and physical therapy. Injections were uneventful with most performed mostly at three or four levels of the lumbar spine with the mean dose of 12.5 mg to 16.7 mg per joint. Approximately 70% of patients responded to treatment with at least 30% self-reported pain improvement and 57.4% responded with at least 50% improvement. These results are clinically significant and are consistent with a previous study of 9 patients receiving AM/UC injection for FJS pain [19]. The majority of patients in that prior study had traumatic etiology involving in the cervical spine, whereas the majority of the patients in the current study had age-related degenerative process in the lumbar spine. Additionally, 66.7% of patients exhibited pain improvement $\geqslant$ 50% at 6 months ( $n=$ 9) and 12 months ( $n=$ 3), respectively, although the sample size for patients with a longer follow up was small.

The clinical application of AM/UC and specifically CLARIX FLO has been demonstrated in a range of indications to promote wound healing in chronic wounds [33], preventing scarring following excision of keloid and hypertrophic scar [34] and release of bladder neck contractures [35] and reducing pain in plantar fasciitis [36], partial rotator cuff tear [37], knee osteoarthritis [20], and peripheral neuropathy [38]. Despite the perceived wide array of uses, these conditions have common underlying etiologies including chronic inflammation and deficient wound healing. Although AM and UC are known to contain multiple ECM components and growth factors/cytokines, research efforts supported by National Institutes of Health (NIH) over the last decade have led to the characterization of HC-HA/PTX3 as the major active tissue component uniquely present in this birth tissue and responsible for their anti-inflammatory, anti-scarring and anti-angiogenic properties [39, 40, 41, 42, 43]. Unlike steroids, HC-HA/PTX3 orchestrates multiple biological actions in several cell types [39, 44]. Its anti-inflammatory action is broader than steroid as it acts on neutrophils, macrophages, and lymphocytes spanning from innate to adaptive immune responses [45, 46]. Furthermore, HC-HA/PTX3 also exerts anti-scarring action to prevent myofibroblast differentiation and reverts human corneal fibroblasts and myofibroblasts to keratocytes through suppression of canonical Smad-mediated TGF- $\beta$ signaling and activation of BMP signaling [47]. Collectively, these actions render HC-HA/PTX3 as the prime candidate in the birth tissue to deliver regenerative healing [39, 44] which may be translated to a lasting benefit.

Although this study provides preliminary findings to support the safety and effectiveness of AM/UC particulate injection in managing FJS pain, there are limitations to note. First, this was a retrospective design and was reliant on patients returning to the office and providing their subjective change in improvement. Furthermore, the sample size for patients with a longer follow up was small. Future randomized studies are warranted to further assess safety and efficacy of AM/UC injection in improving function and relieving FJS pain especially to see if such benefits may last longer than RFA [13].

5. Conclusion

This study supports the safety and effectiveness of AM/UC particulate injection in managing FJS pain. A prospective randomized control trial is warranted.

Footnotes

Conflict of interest

None to report.

References

Hoy

Bain

Williams

March

Brooks

Blyth

, et al. A systematic review of the global prevalence of low back pain. Arthritis & Rheumatism. 2012; 64(6): 2028-37.

United states bone and joint decade: The burden of musculoskeletal diseases in the united states. Rosemont, IL Retrieved August. 2008; 26: 2010.

Saravanakumar

Harvey

. Lumbar zygapophyseal (facet) joint pain. Reviews in Pain. 2008; 2(1): 8-13.

Kalichman

Hunter

, eds. Lumbar facet joint osteoarthritis: a review. Seminars in arthritis and rheumatism; 2007: Elsevier.

Bolesta

Bohlman

. Degenerative spondylolisthesis. Instructional Course Lectures. 1989; 38: 157-65.

Manchikanti

Singh

Pampati

Damron

Barnhill

Beyer

, et al. Evaluation of the relative contributions of various structures in chronic low back pain. Pain Physician. 2001; 4(4): 308-16.

Perolat

Kastler

Nicot

Pellat

Tahon

Attye

, et al. Facet joint syndrome: From diagnosis to interventional management. Insights Imaging. 2018; 9(5): 773-89.

Manchikanti

Boswell

Singh

Pampati

Damron

Beyer

. Prevalence of facet joint pain in chronic spinal pain of cervical, thoracic, and lumbar regions. BMC Musculoskeletal Disorders. 2004; 5(1): 15.

Morlion

. Chronic low back pain: pharmacological, interventional and surgical strategies. Nature Reviews Neurology. 2013; 9(8): 462.

10.

Cohen

Bhaskar

Bhatia

Buvanendran

Deer

Garg

, et al. Consensus practice guidelines on interventions for lumbar facet joint pain from a Multispecialty, International Working group. Regional Anesthesia & Pain Medicine. 2020; 45(6): 424-67.

11.

Snidvongs

Taylor

Ahmad

Thomson

Sharma

Farr

, et al. Facet-joint injections for non-specific low back pain: A feasibility RCT. Health Technology Assessment (Winchester, England). 2017; 21(74): 1.

12.

Gangi

Dietemann

J-L

Mortazavi

Pfleger

Kauff

Roy

. CT-guided interventional procedures for pain management in the lumbosacral spine. Radiographics: A Review Publication of the Radiological Society of North America, Inc. 1998; 18(3): 621-33.

13.

Streitberger

Müller

Eichenberger

Trelle

Curatolo

. Factors determining the success of radiofrequency denervation in lumbar facet joint pain: A prospective study. European Spine Journal. 2011; 20(12): 2160-5.

14.

McCormick

Marshall

Walker

McCarthy

Walega

. Long-term function, pain and medication use outcomes of radiofrequency ablation for lumbar facet syndrome. Int J Anesth Anesth. 2015; 2(2).

15.

Liu

Sheha

Liang

Tseng

. Update on amniotic membrane transplantation. ExpertRevOphthalmol. 2010; 5(5): 645-61.

16.

Dua

Gomes

King

Maharajan

. The amniotic membrane in ophthalmology. SurvOphthalmol. 2004; 49(1): 51-77.

17.

Bouchard

John

. Amniotic membrane transplantation in the management of severe ocular surface disease: Indications and outcomes. OculSurf. 2004; 2(3): 201-11.

18.

Cooke

Tan

Mandrycky

O’Connell

Tseng

. Comparison of cryopreserved amniotic membrane and umbilical cord tissue with dehydrated amniotic membrane/chorion tissue. JWoundCare. 2014; 23(10): 465-76.

19.

Bennett

. Cryopreserved amniotic membrane and umbilical cord particulate for managing pain caused by facet joint syndrome: A case series. Medicine. 2019; 98(10): e14745.

20.

Castellanos

Tighe

. Injectable amniotic membrane/ umbilical cord particulate for knee osteoarthritis: A prospective, single-center pilot study. Pain Med. 2019.

21.

Gellhorn

Katz

Suri

. Osteoarthritis of the spine: The facet joints. NIH Public Access. 2013; 9(4): 216-24.

22.

Fujiwara

Tamai

Yamato

Yoshida

Saotome

, et al. The relationship between facet joint osteoarthritis and disc degeneration of the lumbar spine: An MRI study. Eur Spine J. 1999; 8(5): 396-401.

23.

Weishaupt

Zanetti

Boos

Hodler

. MR imaging and CT in osteoarthritis of the lumbar facet joints. Skeletal radiology. 1999; 28(4): 215-9.

24.

Perolat

Kastler

Nicot

Pellat

J-M

Tahon

Attye

, et al. Facet joint syndrome: From diagnosis to interventional management. Insights into Imaging. 2018; 9(5): 773-89.

25.

Manchikanti

Kaye

Soin

Albers

Beall

Latchaw

, et al. Comprehensive evidence-based guidelines for facet joint interventions in the management of chronic spinal pain: American society of interventional pain physicians (ASIPP) guidelines facet joint interventions 2020 guidelines. Pain Physician. 2020; 23(3s): S1-s127.

26.

Theodore

Olamikan

Keith

Gofeld

. Validation of self-reported pain reduction after diagnostic blockade. Pain Medicine. 2012; 13(9): 1131-6.

27.

Farrar

Young

Jr LaMoreaux

Werth

Poole

. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001; 94(2): 149-58.

28.

Chou

Deyo

Friedly

Skelly

Weimer

, et al. Systemic pharmacologic therapies for low back pain: A systematic review for an American College of Physicians clinical practice guideline. Annals of Internal Medicine. 2017; 166(7): 480-92.

29.

Licciardone

Gatchel

Aryal

. Targeting patient subgroups with chronic low back pain for osteopathic manipulative treatment: responder analyses from a randomized controlled trial. J Am Osteopath Assoc. 2016; 116(3): 156-68.

30.

Manchikanti

Manchukonda

Cash

Damron

Pampati

, et al. Evaluation of lumbar facet joint nerve blocks in the management of chronic low back pain: A preliminary report of a randomized, double-blind controlled trial: Clinical trial NCT00355914. Pain Physician. 2007; 10(3): 425.

31.

Sutovsky

Benco

Sutovska

Kocmalova

Pappova

Miklusica

, et al. Cytokine and chemokine profile changes in patients with lower segment lumbar degenerative spondylolisthesis. International Journal of Surgery (London, England). 2017; 43: 163-70.

32.

Igarashi

Kikuchi

Konno

Olmarker

. Inflammatory cytokines released from the facet joint tissue in degenerative lumbar spinal disorders. Spine. 2004; 29(19): 2091-5.

33.

Swan

. Use of cryopreserved, particulate human amniotic membrane and umbilical cord (AM/UC) tissue: A case series study for application in the healing of chronic wounds. Surgical Technology International. 2014; 25: 73-8.

34.

B D, E T, H P, F Y, H P. Amniotic and umbilical cord particulate in the management of keloid and hypertrophic scars. Wound Central. 2019.

35.

Munver*

Desroches

. MP04-13 use of a human amniotic membrane and umbilical cord regenerative matrix for the management of recalcitrant bladder neck contractures. The Journal of Urology. 2020; 203(Supplement 4): e37-e.

36.

Garras

Scott

. Particulate umbilical cord/amniotic membrane for the treatment of plantar fasciitis. Foot & Ankle Orthopaedics. 2017; 2(3): 2473011417S000174.

37.

Ackley

Kolosky

Gurin

Hampton

Masin

Krahe

. Cryopreserved amniotic membrane and umbilical cord particulate matrix for partial rotator cuff tears: A case series. Medicine (Baltimore). 2019; 98(30): e16569.

38.

Buksh

. Ultrasound-guided Injections of Amniotic Membrane/Umbilical Cord Particulate for Painful Neuropathy of the Lower Extremity. Manuscript in Draft.

39.

Tighe

Mead

Lee

Tseng

. Basic Science Review of Birth Tissue Uses in Ophthalmology. Taiwan Journal of Ophthalmology. 2020; 10.

40.

Tseng

. HC-HA/PTX3 purified from amniotic membrane as novel regenerative matrix: Insight into relationship between inflammation and regeneration. Invest Ophthalmol Vis Sci. 2016; 57(5): ORSFh1-8.

41.

Tseng

Zhang

Chen

Day

, et al. Biochemical characterization and function of complexes formed by hyaluronan and the heavy chains of inter-alpha-inhibitor (HC*HA) purified from extracts of human amniotic membrane. J Biol Chem. 2009; 284(30): 20136-46.

42.

Zhang

Zhu

Chen

Tseng

. Constitutive expression of pentraxin 3 (PTX3) protein by human amniotic membrane cells leads to formation of the heavy chain (HC)-hyaluronan (HA)-PTX3 complex. J Biol Chem. 2014; 289(19): 13531-42.

43.

Shay

Sakurai

Tseng

. Inhibition of angiogenesis by HC.HA, a complex of hyaluronan and the heavy chain of inter-alpha-inhibitor, purified from human amniotic membrane. Invest OphthalmolVisSci. 2011; 52(5): 2669-78.

44.

Tseng

. HC-HA/PTX3 purified from amniotic membrane as novel regenerative matrix: Insight into relationship between inflammation and regeneration. IOVS. 2016; 57(5).

45.

Zhang

Tighe

Son

Tseng

. Immobilized heavy chain-hyaluronic acid polarizes lipopolysaccharide-activated macrophages toward M2 phenotype. J Biol Chem. 2013; 288(36): 25792-803.

46.

Tan

Duffort

Perez

Tseng

. In vivo downregulation of innate and adaptive immune responses in corneal allograft rejection by HC-HA/PTX3 complex purified from amniotic membrane. Investigative Ophthalmology & Visual Science. 2014; 55(3): 1647-56.

47.

Zhu

Y-TL

, Fu; Zhang, Yuan; Chen, Szu-Yu; Tighe, Sean; Lin, Shin-Ying and Tseng, Scheffer C.G. HC-HA/PTX3 purified from human amniotic membrane reverts human corneal fibroblasts and myofibroblasts to keratocytes by activating bmp signaling. Invest Ophthalmol Vis Sci (In press). 2020.

Injectable amniotic membrane/umbilical cord particulate for facet joint syndrome: A retrospective,single-center study

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Introduction

2. Methods

2.1 Patients

2.2 Treatment with AM/UC

2.3 Post-injection care

2.4 Outcome measures

2.5 Statistical analysis

3. Results

Table 1 Association between demographics and response to treatment

5. Conclusion

Footnotes

Conflict of interest

References

Table 1
Association between demographics and response to treatment